bluuebunny/crossref_metadata_2025 huggingface dataset:
Cross-Reactive SARS-CoV-2 Neutralizing Antibodies From Deep Mining of Early Patient Responses
Authors: Bullen Georgia , Galson Jacob D. , Hall Gareth , Villar Pedro , Moreels Lien , Ledsgaard Line , Mattiuzzo Giada , Bentley Emma M. , Masters Edward W. , Tang David , Millett Sophie , Tongue Danielle , Brown Richard , Diamantopoulos Ioannis , Parthiban Kothai , Tebbutt Claire , Leah Rachael , Chaitanya Krishna , Ergueta-Carballo Sandra , Pazeraitis Deividas , Surade Sachin B. , Ashiru Omodele , Crippa Lucia , Cowan Richard , Bowler Matthew W. , Campbell Jamie I. , Lee Wing-Yiu Jason , Carr Mark D. , Matthews David , Pfeffer Paul , Hufton Simon E. , Sawmynaden Kovilen , Osbourn Jane , McCafferty John , Karatt-Vellatt Aneesh
Published: June 2021

Passive immunization using monoclonal antibodies will play a vital role in the fight against COVID-19. The recent emergence of viral variants with reduced sensitivity to some current antibodies and vaccines highlights the importance of broad cross-reactivity. This study describes deep-mining of the antibody repertoires of hospitalized COVID-19 patients using phage display technology and B cell receptor (BCR) repertoire sequencing to isolate neutralizing antibodies and gain insights into the early antibody response. This comprehensive discovery approach has yielded a panel of potent neutralizing antibodies which bind distinct viral epitopes including epitopes conserved in SARS-CoV-1. Structural determination of a non-ACE2 receptor blocking antibody reveals a previously undescribed binding epitope, which is unlikely to be affected by the mutations in any of the recently reported major viral variants including B.1.1.7 (from the UK), B.1.351 (from South Africa) and B.1.1.28 (from Brazil). Finally, by combining sequences of the RBD binding and neutralizing antibodies with the B cell receptor repertoire sequencing, we also describe a highly convergent early antibody response. Similar IgM-derived sequences occur within this study group and also within patient responses described by multiple independent studies published previously.
Strategies to Use Nanoparticles to Generate CD4 and CD8 Regulatory T Cells for the Treatment of SLE and Other Autoimmune Diseases
Authors: Horwitz David A. , Bickerton Sean , La Cava Antonio
Published: June 2021

Autoimmune diseases are disorders of immune regulation where the mechanisms responsible for self-tolerance break down and pathologic T cells overcome the protective effects of T regulatory cells (Tregs) that normally control them. The result can be the initiation of chronic inflammatory diseases. Systemic lupus erythematosus (SLE) and other autoimmune diseases are generally treated with pharmacologic or biological agents that have broad suppressive effects. These agents can halt disease progression, yet rarely cure while carrying serious adverse side effects. Recently, nanoparticles have been engineered to correct homeostatic regulatory defects and regenerate therapeutic antigen-specific Tregs. Some approaches have used nanoparticles targeted to antigen presenting cells to switch their support from pathogenic T cells to protective Tregs. Others have used nanoparticles targeted directly to T cells for the induction and expansion of CD4+ and CD8+ Tregs. Some of these T cell targeted nanoparticles have been formulated to act as tolerogenic artificial antigen presenting cells. This article discusses the properties of these various nanoparticle formulations and the strategies to use them in the treatment of autoimmune diseases. The restoration and maintenance of Treg predominance over effector cells should promote long-term autoimmune disease remission and ultimately prevent them in susceptible individuals.
The Placental Response to Guinea Pig Cytomegalovirus Depends Upon the Timing of Maternal Infection
Authors: Berkebile Zachary W. , Putri Dira S. , Abrahante Juan E. , Seelig Davis M. , Schleiss Mark R. , Bierle Craig J.
Published: June 2021

Human cytomegalovirus (HCMV) infects the placenta, and these placental infections can cause fetal injury and/or demise. The timing of maternal HCMV infection during pregnancy is a determinant of fetal outcomes, but how development affects the placenta’s susceptibility to infection, the likelihood of placental injury post-infection, and the frequency of transplacental HCMV transmission remains unclear. In this study, guinea pig cytomegalovirus (GPCMV) was used to model primary maternal infection and compare the effects of infection at two different times on the placenta. When guinea pigs were infected with GPCMV at either 21- or 35-days gestation (dGA), maternal and placental viral loads, as determined by droplet digital PCR, were not significantly affected by the timing of maternal infection. However, when the transcriptomes of gestational age-matched GPCMV-infected and control placentas were compared, significant infection-associated changes in gene expression were only observed after maternal infection at 35 dGA. Notably, transcripts associated with immune activation (e.g. Cxcl10, Ido1, Tgtp1, and Tlr8) were upregulated in the infected placenta. A GPCMV-specific in situ hybridization assay detected rare infected cells in the main placenta after maternal infection at either time, and maternal infection at 35 dGA also caused large areas of GPCMV-infected cells in the junctional zone. As GPCMV infection after mid-gestation is known to cause high rates of stillbirth and/or fetal growth restriction, our results suggest that the placenta becomes sensitized to infection-associated injury late in gestation, conferring an increased risk of adverse pregnancy outcomes after cytomegalovirus infection.
Mucosal Immunization Against Pertussis: Lessons From the Past and Perspectives
Authors: Dubois Violaine , Locht Camille
Published: June 2021

Background

Current vaccination strategies against pertussis are sub-optimal. Optimal protection against Bordetella pertussis, the causative agent of pertussis, likely requires mucosal immunity. Current pertussis vaccines consist of inactivated whole B. pertussis cells or purified antigens thereof, combined with diphtheria and tetanus toxoids. Although they are highly protective against severe pertussis disease, they fail to elicit mucosal immunity. Compared to natural infection, immune responses following immunization are short-lived and fail to prevent bacterial colonization of the upper respiratory tract. To overcome these shortcomings, efforts have been made for decades, and continue to be made, toward the development of mucosal vaccines against pertussis.

Objectives

In this review we systematically analyzed published literature on protection conferred by mucosal immunization against pertussis. Immune responses mounted by these vaccines are summarized.

Method

The PubMed Library database was searched for published studies on mucosal pertussis vaccines. Eligibility criteria included mucosal administration and the evaluation of at least one outcome related to efficacy, immunogenicity and safety.

Results

While over 349 publications were identified by the search, only 63 studies met the eligibility criteria. All eligible studies are included here. Initial attempts of mucosal whole-cell vaccine administration in humans provided promising results, but were not followed up. More recently, diverse vaccination strategies have been tested, including non-replicating and replicating vaccine candidates given by three different mucosal routes: orally, nasally or rectally. Several adjuvants and particulate formulations were tested to enhance the efficacy of non-replicating vaccines administered mucosally. Most novel vaccine candidates were only tested in animal models, mainly mice. Only one novel mucosal vaccine candidate was tested in baboons and in human trials.

Conclusion

Three vaccination strategies drew our attention, as they provided protective and durable immunity in the respiratory tract, including the upper respiratory tract: acellular vaccines adjuvanted with lipopeptide LP1569 and c-di-GMP, outer membrane vesicles and the live attenuated BPZE1 vaccine. Among all experimental vaccines, BPZE1 is the only one that has advanced into clinical development.
Mediterranean Coral Provinces as a Sponge Diversity Reservoir: Is There a Mediterranean Cold-Water Coral Sponge Fauna?
Authors: Santín Andreu , Grinyó Jordi , Uriz Maria Jesús , Lo Iacono Claudio , Gili Josep Maria , Puig Pere
Published: June 2021

Cold-water coral reefs (CWC) are known to be biodiversity hotspots, however, the sponge assemblages found to dwell within these habitats haven not been studied in depth to date in the Mediterranean Sea. The present article provides the first insight on the associated sponge fauna of the recently discovered CWC communities on the Catalan Margin and, to a lesser extent, the Cabliers Coral Mound Province, while also reviewing the current knowledge of the sponge fauna dwelling in all the Mediterranean CWC provinces. In regards to the studied areas, some rare species are cited for the first time in the Mediterranean or redescribed, while two of them, Hamacantha (Hamacantha) hortae sp. nov. and Spongosorites cabliersi sp. nov. are new to science. At a basin scale, Mediterranean CWC appear as poriferan biodiversity hotspots, yet current diversity values on each site rather represent a small fraction of its actual fauna. Additionally, the existence of an endemic sponge fauna exclusively dwelling on CWC is refuted. Nonetheless, the sponge fauna thriving in Mediterranean CWC appears to be unique, and different from that of other Atlantic regions. Finally, with the current knowledge, the sponge fauna from the Mediterranean CWC is grouped in three distinguishable clusters (Alboran Sea, Western and Eastern Mediterranean), which appears to be determined by the basins water circulation, specially the Levantine Intermediate Water and the Atlantic Water following a western-eastern pattern from the Strait of Gibraltar to the Adriatic Sea. Overall, sponge living in Mediterranean CWC are still poorly explored in most areas, yet they appear to be good candidates for biogeographical studies.

Zoobank Registration: LSID urn:lsid:zoobank.org:pub:E58A3DFF-EDC5-44FC-A274-1C9508BF8D15.
Detecting Climate Signals in Southern Ocean Krill Growth Habitat
Authors: Sylvester Zephyr T. , Long Matthew C. , Brooks Cassandra M.
Published: June 2021

Climate change is rapidly altering the habitat of Antarctic krill (Euphausia superba), a key species of the Southern Ocean food web. Krill are a critical element of Southern Ocean ecosystems as well as biogeochemical cycles, while also supporting an international commercial fishery. In addition to trends forced by global-scale, human-driven warming, the Southern Ocean is highly dynamic, displaying large fluctuations in surface climate on interannual to decadal timescales. The dual roles of forced climate change and natural variability affecting Antarctic krill habitat, and therefore productivity, complicate interplay of observed trends and contribute to uncertainty in future projections. We use the Community Earth System Model Large Ensemble (CESM-LE) coupled with an empirically derived model of krill growth to detect and attribute trends associated with “forced,” human-driven climate change, distinguishing these from variability arising naturally. The forced trend in krill growth is characterized by a poleward contraction of optimal conditions and an overall reduction in Southern Ocean krill habitat. However, the amplitude of natural climate variability is relatively large, such that the forced trend cannot be formally distinguished from natural variability at local scales over much of the Southern Ocean by 2100. Our results illustrate how natural variability is an important driver of regional krill growth trends and can mask the forced trend until late in the 21st century. Given the ecological and commercial global importance of krill, this research helps inform current and future Southern Ocean krill management in the context of climate variability and change.
Using the LBB Method for the Assessments of Seven Fish Stocks From the Yangtze Estuary and Its Adjacent Waters
Authors: Wang Yuanchao , Liang Cui , Xian Weiwei , Wang Yibang
Published: June 2021

The status of fishery resources in the Yangtze estuary and its adjacent waters is still unclear for the effective implementation of fishery management strategies. To help address this gap, a new method especially for data-limited fish stocks (LBB) was applied to assess seven commercially and ecotrophically important fish stocks. Fish specimens were collected in the estuary by bottom trawling quarterly from May 2018 to February 2019. Two historical datasets were collected with the same method in the same area for Indian perch (Jaydia lineata) and sickle pomfret (Pampus echinogaster). To explore the growth features and resilience of fish stocks, auximetric plots and growth performance indices (Φ′) were used. Results showed that common hairfin anchovy (Setipinna tenuifilis) in 2018 and Indian perch in 2018 showed a healthy stock biomass status with complete length structures under a sustainable fishing pressure. The others were outside of safe biological limits or overfished. TheLmean/Lopt< 0.9 in six (67%) of nine LBB models for seven fish stocks suggested that most of the stocks were truncated in length structures. This contribution provides the main fishery reference points regarding stock status that can inform managers and form the basis for various management strategies.
Perinatal Nutritional and Metabolic Pathways: Early Origins of Chronic Lung Diseases
Authors: Kuiper-Makris Celien , Selle Jaco , Nüsken Eva , Dötsch Jörg , Alejandre Alcazar Miguel A.
Published: June 2021

Lung development is not completed at birth, but expands beyond infancy, rendering the lung highly susceptible to injury. Exposure to various influences during a critical window of organ growth can interfere with the finely-tuned process of development and induce pathological processes with aberrant alveolarization and long-term structural and functional sequelae. This concept of developmental origins of chronic disease has been coined as perinatal programming. Some adverse perinatal factors, including prematurity along with respiratory support, are well-recognized to induce bronchopulmonary dysplasia (BPD), a neonatal chronic lung disease that is characterized by arrest of alveolar and microvascular formation as well as lung matrix remodeling. While the pathogenesis of various experimental models focus on oxygen toxicity, mechanical ventilation and inflammation, the role of nutrition before and after birth remain poorly investigated. There is accumulating clinical and experimental evidence that intrauterine growth restriction (IUGR) as a consequence of limited nutritive supply due to placental insufficiency or maternal malnutrition is a major risk factor for BPD and impaired lung function later in life. In contrast, a surplus of nutrition with perinatal maternal obesity, accelerated postnatal weight gain and early childhood obesity is associated with wheezing and adverse clinical course of chronic lung diseases, such as asthma. While the link between perinatal nutrition and lung health has been described, the underlying mechanisms remain poorly understood. There are initial data showing that inflammatory and nutrient sensing processes are involved in programming of alveolarization, pulmonary angiogenesis, and composition of extracellular matrix. Here, we provide a comprehensive overview of the current knowledge regarding the impact of perinatal metabolism and nutrition on the lung and beyond the cardiopulmonary system as well as possible mechanisms determining the individual susceptibility to CLD early in life. We aim to emphasize the importance of unraveling the mechanisms of perinatal metabolic programming to develop novel preventive and therapeutic avenues.
A Comparison of Treatment Options for Type 1 and Type 2 Caesarean Scar Pregnancy: A Retrospective Case Series Study
Authors: Shen Fanghua , Lv Hongdao , Wang Liming , Zhao Ruiheng , Tong Mancy , Lee Arier Chi-Lun , Guo Fang , Chen Qi
Published: June 2021

Background: There is currently no agreement on the optimal management of caesarean scar pregnancy. Caesarean scar pregnancy is currently categorised into two subtypes according to the site of implantation. This may consequently result in the difference in treatment options. However, the comparison of the success rate of each treatment option according to the subtypes has not been fully investigated.

Methods: 71 patients who were treated by uterine curettage (D and C), or uterine artery embolization with curettage (UAE) or hysteroscopy in conjunction with laparoscopy between January 2016 and March 2020 were included. Data on maternal age, gestational sac age, the sac diameter, the interval between two pregnancies, the number of previous caesarean sections, amount of bleeding and β-hCG levels were collected and analysed dependent on the subtypes.

Results: There was no difference in the clinical parameters of the cases who received different options of treatment, as well as no difference in the clinical parameters between type 1 and type 2 caesarean scar pregnancy. The primary success rate for type 1 caesarean scar pregnancy by D and C, or UAE, or hysteroscopy in conjunction with laparoscopy was 95, or 100 or 100%, respectively. The primary success rate for type 2 caesarean scar pregnancy by D and C, or UAE, or hysteroscopy in conjunction with laparoscopy was 27, or 67, or 95% respectively.

Conclusion: Our data demonstrates that hysteroscopy in conjunction with laparoscopy for type 2 caesarean scar pregnancy was the most successful compared to other options, but for type 1 caesarean scar pregnancy, D and C could be the cost-effective option.
308-nm Excimer Lamp vs. Combination of 308-nm Excimer Lamp and 10% Liquor Carbonis Detergens in Patients With Scalp Psoriasis: A Randomized, Single-Blinded, Controlled Trial
Authors: Rattanakaemakorn Ploysyne , Triyangkulsri Korn , Iamsumang Wimolsiri , Suchonwanit Poonkiat
Published: June 2021

Background: Scalp psoriasis is usually refractory to treatment. Excimer devices have been proved to be a promising therapeutic option in psoriasis. Greater efficacy of phototherapy can be achieved by concurrent use of coal tar derivatives.

Objective: We aimed to compare efficacy and safety between 308-nm excimer lamp monotherapy and a combination of 308-nm excimer lamp and 10% liquor carbonis detergens in the treatment of scalp psoriasis.

Methods: In this randomized, evaluator-blinded, prospective, comparative study, 30 patients with scalp psoriasis received either 308-nm excimer lamp monotherapy or a combination of 308-nm excimer lamp and 10% liquor carbonis detergens twice per week until complete remission of the scalp or for a total of 30 sessions. Efficacy was evaluated by the improvement of Psoriasis Scalp Severity Index (PSSI) score, itch score, and Scalpdex score.

Results: Both treatments induced significant improvement in PSSI score with greater reduction observed in the combination group. At 30th visit, a 75% reduction in PSSI (PSSI75) was attained by 4 (28.6%) and 9 (69.2%) patients treated with monotherapy and combination therapy, respectively (P < 0.05).

Conclusions: Excimer lamp is well-tolerated in patients with scalp psoriasis and liquor carbonis detergens can be used as a combination therapy to improve the efficacy of excimer lamp.
Dried Blood Specimens as an Alternative Specimen for Immune Response Monitoring During HIV Infection: A Proof of Concept and Simple Method in a Pediatric Cohort
Authors: Rubio-Garrido Marina , Avendaño-Ortiz José , Ndarabu Adolphe , Rubio Carolina , Reina Gabriel , López-Collazo Eduardo , Holguín África
Published: June 2021

Programs to prevent mother-to-child HIV transmission do not reduce the number of infants exposed during pregnancy and breastfeeding. HIV-exposed but uninfected children (HEU) present higher risk of morbidity and mortality than HIV-unexposed and uninfected children (UU). In this line, the study of immune biomarkers in HIV could improve prediction of disease progression, allowing to diminish comorbidity risk. Dried blood specimens (DBS) are an alternative to serum for collecting and transporting samples in countries with limited infrastructure and especially interesting for groups such as pediatrics, where obtaining a high sample volume is challenging. This study explores the usefulness of DBS for immune profile monitoring in samples from 30 children under clinical follow-up in Kinshasa: 10 HIV-infected (HIV+), 10 HEU, and 10 UU. We have measured the gene expression levels of 12 immune and inflammatory markers (CD14, IL-6, TNFα, HVEM, B7.1, HIF-1α, Siglec-10, IRAK-M, CD163, B7H5, PD-L1, and Galectin-9) in DBS samples by reverse transcription of total RNA and RT-qPCR. Principal component analysis, Kruskal–Wallis test, and Mann–Whitney test were performed in order to study group differences. HIV+ children presented significantly higher levels of seven biomarkers (CD14, IL-6 HVEM, B7.1, Siglec-10, HIF-1α, and CD163) than the UU group. In HEU, we found seven biomarkers significantly elevated (CD14, IL-6, HVEM, B7.1, Siglec-10, HIF-1α, and IRAK-M) vs. UU. Six biomarkers (CD14, IL-6, HVEM, B7.1, Siglec-10, and HIF-1α) showed a significantly higher expression in both HIV+ and HEU vs. UU, with HVEM and CD14 being significantly overexpressed among HIV+ vs. HEU. Our data reveal the utility of DBS for immune response monitoring. Moreover, significant differences in specific biomarker expression across groups strongly suggest the effect of HIV infection and/or HIV exposure on these immune biomarkers' expressions.
Comparison of Retention Rates Between Tumor Necrosis Factor-α Inhibitors in Patients With Ankylosing Spondylitis: Data From the Korean College of Rheumatology Biologics Registry
Authors: Kim Hyoun-Ah , Lee Sun-Kyung , Oh Sohee , Park Eun Hye , Park Yong-Beom , Shin Kichul
Published: June 2021

This study aimed to investigate drug retention rates for various TNF inhibitors (TNFis) commonly prescribed to Korean patients with ankylosing spondylitis (AS) in the Korean College of Rheumatology Biologics registry (KOBIO; December 2012–June 2016). Discontinuation was defined as switching or stopping the biologic agent. Kaplan–Meier curves and Cox's proportional hazard models were used for further analysis. The reasons for discontinuation of TNFis were also assessed. Univariate and multivariate analyses were used to identify possible predictors of discontinuation. Data from 1,005 patients with AS were analyzed with a median follow-up period of 14 months. Seventy-six percent of patients were first-line biologic users. Discontinuation of TNFis occurred in 24.2% (switching in 9.6%) of patients during follow-up. An estimate of the drug failure showed that the adjusted hazard ratio (HR) for golimumab compared to etanercept was 0.441 (95% confidence interval: 0.277–0.703, p < 0.001). Reasons for discontinuation included lack of efficacy (32.6%), adverse events (23.6%), clinical improvement (11.2%), and others (32.6%). Predictors of discontinuation using a multivariate analysis were a shorter disease duration (HR: 0.973, p = 0.044) and being negative for HLA-B27 (HR: 1.623, p = 0.0093). In conclusion, few Korean patients with AS switched to other TNFis during their treatment. The drug retention rate for golimumab was higher than for other agents.
Maternal Microbiota Transfer Programs Offspring Eating Behavior
Authors: Pocheron Anne-Lise , Le Dréan Gwenola , Billard Helene , Moyon Thomas , Pagniez Anthony , Heberden Christine , Le Chatelier Emmanuelle , Darmaun Dominique , Michel Catherine , Parnet Patricia
Published: June 2021

Understanding the link between mother’s obesity and regulation of the child’s appetite is a prerequisite for the design of successful preventive strategies. Beyond the possible contributions of genetic heritage, family culture, and hormonal and metabolic environment during pregnancy, we investigate in the present paper the causal role of the transmission of the maternal microbiotas in obesity as microbiotas differ between lean and obese mothers, maternal microbiotas are the main determinants of a baby’s gut colonization, and the intestinal microbiota resulting from the early colonization could impact the feeding behavior of the offspring with short- and long-term consequences on body weight. We thus investigated the potential role of vertical transfers of maternal microbiotas in programming the eating behavior of the offspring. Selectively bred obese-prone (OP)/obese-resistant (OR) Sprague-Dawley dams were used since differences in the cecal microbiota have been evidenced from males of that strain. Microbiota collected from vagina (at the end of gestation), feces, and milk (at postnatal days 1, 5, 10, and 15) of OP/OR dams were orally inoculated to conventional Fischer F344 recipient pups from birth to 15 days of age to create three groups of pups: F-OP, F-OR, and F-Sham group (that received the vehicle). We first checked microbiotal differences between inoculas. We then assessed the impact of transfer (from birth to adulthood) onto the intestinal microbiota of recipients rats, their growth, and their eating behavior by measuring their caloric intake, their anticipatory food reward responses, their preference for sweet and fat tastes in solutions, and the sensations that extend after food ingestion. Finally, we searched for correlation between microbiota composition and food intake parameters. We found that maternal transfer of microbiota differing in composition led to alterations in pups’ gut microbiota composition that did not last until adulthood but were associated with specific eating behavior characteristics that were predisposing F-OP rats to higher risk of over consuming at subsequent periods of their life. These findings support the view that neonatal gut microbiotal transfer can program eating behavior, even without a significant long-lasting impact on adulthood microbiota composition.
Promoting Healthy Eating Behaviors by Incentivizing Exploration of Healthy Alternatives
Authors: Shavit Yael , Roth Yefim , Teodorescu Kinneret
Published: June 2021

Incentive-based intervention programs aimed at promoting healthy eating behaviors usually focus on incentivizing repeating the desired behavior. Unfortunately, even when effective, these interventions are often short-lived and do not lead to a lasting behavioral change. We present a new type of intervention program focused on incentivizing exploration of new healthy alternatives rather than incentivizing repeated healthy behaviors. This intervention aims to help participants find long-lasting “personal treasures” —new foods that are both healthy and tasty for them. Our field study included a final sample of 48 students with low or medium daily consumption of fresh salads. Participants in the control group received a fixed payment for completing the program, while the participants in the incentivized exploration group received a lower fixed fee for completing the task and a bonus for each new salad they tried. Results show that participants in the incentivized exploration group reported eating more salads even 1 year after the program ended compared to the participants in the control group. Though preliminary, our results paint a promising picture for the successful application of incentivizing exploration interventions to promote healthy lifestyle.
A Prognosis Marker SLC2A3 Correlates With EMT and Immune Signature in Colorectal Cancer
Authors: Gao Huabin , Liang Jiangtao , Duan Jing , Chen Lin , Li Hui , Zhen Tiantian , Zhang Fenfen , Dong Yu , Shi Huijuan , Han Anjia
Published: June 2021

SLC2A3 is a membrane transporter that belongs to the solute carrier family, whose function includes transmembrane transport and glucose transmembrane transport activity. To clarify the expression and role of SLC2A3 in colorectal cancer (CRC), we analyzed the TCGA and GEO databases and found that SLC2A3 mRNA levels were significantly higher in CRC tissues than that in adjacent non-tumor tissues. Furthermore, high expression of SLC2A3 predicted poor overall survival and disease free survival for CRC patients. For validation, we collected 174 CRC samples and found that SLC2A3 expression was higher in CRC tissues than that in adjacent non-tumor colorectal mucosa tissues by immunohistochemistry staining. Further study showed that high expression of SLC2A3 was enriched in epithelial–mesenchymal transition (EMT) classical pathway, interferon-γ pathway by GSEA analysis enrichment, indicating that SLC2A3 may play a key role in the progression of CRC through EMT and immune response, which also has been validated by the global gene expression profiling of human CRC cell lines. The expression of SLC2A3 was positively correlated with CD4 and CD8+T cells by using TIMER and EPIC algorithm, respectively. SLC2A3 knockdown suppressed migration and inhibited the expression of Vimentin and MMP9 in CRC cell line SW480 and RKO. Meanwhile, PD-L1 expression was also significantly attenuated in SW480 and RKO cells transfected with SLC2A3 siRNA. The result suggests that SLC2A3 may be involved in the immune response of CRC by regulating PD-L1 immune checkpoint. In our series, SLC2A3 and PD-L1 positive expression was 74% (128/174) and 22% (39/174) of CRC, respectively. SLC2A3 expression was significantly associated with perineural invasion in CRC patients. In conclusion, SLC2A3 may play an important role in progression of CRC by regulating EMT and PD-L1 mediated immune responses.
Cost-Effectiveness Analysis of Local Treatment in Oligometastatic Disease
Authors: Mehrens Dirk , Unterrainer Marcus , Corradini Stefanie , Niyazi Maximilian , Manapov Farkhad , Westphalen C. Benedikt , Froelich Matthias F. , Wildgruber Moritz , Seidensticker Max , Ricke Jens , Rübenthaler Johannes , Kunz Wolfgang G.
Published: June 2021

Background

In certain malignancies, patients with oligometastatic disease benefit from radical ablative or surgical treatment. The SABR-COMET trial demonstrated a survival benefit for oligometastatic patients randomized to local stereotactic ablative radiation (SABR) compared to patients receiving standard care (SC) alone. Our aim was to determine the cost-effectiveness of SABR.

Materials and Methods

A decision model based on partitioned survival simulations estimated costs and quality-adjusted life years (QALY) associated with both strategies in a United States setting from a health care perspective. Analyses were performed over the trial duration of six years as well as a long-term horizon of 16 years. Model input parameters were based on the SABR-COMET trial data as well as best available and most recent data provided in the published literature. An annual discount of 3% for costs was implemented in the analysis. All costs were adjusted to 2019 US Dollars according to the United States Consumer Price Index. SABR costs were reported with an average of $11,700 per treatment. Deterministic and probabilistic sensitivity analyses were performed. Incremental costs, effectiveness, and cost-effectiveness ratios (ICER) were calculated. The willingness-to-pay (WTP) threshold was set to $100,000/QALY.

Results

Based on increased overall and progression-free survival, the SABR group showed 0.78 incremental QALYs over the trial duration and 1.34 incremental QALYs over the long-term analysis. Treatment with SABR led to a marginal increase in costs compared to SC alone (SABR: $304,656; SC: $303,523 for 6 years; ICER $1,446/QALY and SABR: $402,888; SC: $350,708 for long-term analysis; ICER $38,874/QALY). Therapy with SABR remained cost-effective until treatment costs of $88,969 over the trial duration (i.e. 7.6 times the average cost). Sensitivity analysis identified a strong model impact for ongoing annual costs of oligo- and polymetastatic disease states.

Conclusion

Our analysis suggests that local treatment with SABR adds QALYs for patients with certain oligometastatic cancers and represents an intermediate- and long-term cost-effective treatment strategy.
Flow Cytometry-Assessed PD1/PDL1 Status in Tumor-Infiltrating Lymphocytes: A Link With the Prognosis of Diffuse Large B-Cell Lymphoma
Authors: Chen Zihang , Deng Xueqin , Ye Yunxia , Zhang Wenyan , Liu Weiping , Zhao Sha
Published: June 2021

The PD1/PDL1 status of tumor-infiltrating lymphocytes (TILs) in diffuse large B-cell lymphoma (DLBCL) reflects immune function. However, the previously reported methods for evaluating this status are complex and may not be widely used in clinical practice. In addition, these studies did not introduce healthy controls to designate the cut-off when evaluating the prognostic value of the status. In this study, we retrospectively evaluated the PD1/PDL1 status in TILs of 24 DLBCL tissue samples and normal immune cells in 61 demographically matched healthy controls (tissue samples from patients with reactive hyperplasia [RH]) by flow cytometry. We investigated the prognostic value of the PD1/PDL1 status in TILs by precisely determining the cut-off value and assessing the reliability of flow cytometry. The mean fluorescence intensity (MFI) of PD1 in TIL-T-cells (TIL-Ts; median, 110) and CD8+TIL-Ts (median, 64) was significantly higher than that of CD3+T-cells (median, 64) and CD8+ T-cells (median, 34) in RH. The cut-off values of PD1/PDL1 status for analyzing prognostic values were defined considering the PD1/PDL1 status of samples from both patients with DLBCL and healthy controls. High MFI of PD1 in TIL-Ts (MFI >108, P = 0.022), high proportion of PD1+CD4+TIL-Ts (>1.1% of CD4+TIL-Ts, P = 0.049), high proportion of PD1+CD8+TIL-Ts (>2% of CD8+TIL-Ts, P = 0.025), and high MFI of PDL1 in TIL-Ts (MFI >83, P = 0.023) were risk factors for inferior prognosis of DLBCL. Our results indicate that flow cytometry is a reliable and convenient method for evaluating the immune-checkpoint status of TILs, which probably holds major implications in clinical practice.
Case Report: Pink Urine Syndrome Following Exposure to Propofol: A Rare, Impressive but Benign Complication
Authors: Zhang Fangwei , Zhu Xing , Zhang Hongbo , Xu Lin , Wu Weiguo , Hu Xuelei , Zhou Haipeng , Wei Penghui , Li Jianjun
Published: June 2021

Drug-induced changes in urine color induced by drugs may have clinical significance. Pink urine syndrome (PUS), which has been associated with urinary uric acid (UA) disorders, is most frequently reported in patients with morbid obesity undergoing gastric bypass surgery and/or from propofol anesthesia use in those who potentially have preexisting UA metabolism disorders. However, PUS has rarely occurred following exposure to propofol in non-obese patients, and literature on long-term follow-up after PUS is scarce. We report a case of PUS induced by propofol in a previously healthy non-obese woman after undergoing thoracoscopic wedge resection of pulmonary nodules under general anesthesia using propofol. The patient suddenly developed pink urine 4 h after surgery. A pink sediment rapidly precipitated at the bottom of the test tube following centrifugation of the urine. Amorphous, colorless UA-like crystals were identified under a polarizing microscope. The diagnosis of PUS was confirmed by examining the urinary UA concentration. The patient recovered and as followed-up for 1 month, during which she did not experience any urinary complications. To our knowledge, this is the first report to describe in detail a case of PUS caused by propofol in a non-obese patient with follow-up. PUS is usually benign and can resolve by rapidly on administering lactated Ringer’s solution; however, the potential risk of urinary complications, particularly UA lithiasis, should be fully realized.
The Mitochondrial Na+/Ca2+ Exchanger Inhibitor CGP37157 Preserves Muscle Structure and Function to Increase Lifespan and Healthspan in Caenorhabditis elegans
Authors: García-Casas Paloma , Alvarez-Illera Pilar , Gómez-Orte Eva , Cabello Juan , Fonteriz Rosalba I. , Montero Mayte , Alvarez Javier
Published: June 2021

We have reported recently that the mitochondrial Na+/Ca2+ exchanger inhibitor CGP37157 extends lifespan in Caenorhabditis elegans by a mechanism involving mitochondria, the TOR pathway and the insulin/IGF1 pathway. Here we show that CGP37157 significantly improved the evolution with age of the sarcomeric regular structure, delaying development of sarcopenia in C. elegans body wall muscle and increasing the average and maximum speed of the worms. Similarly, CGP37157 favored the maintenance of a regular mitochondrial structure during aging. We have also investigated further the mechanism of the effect of CGP37157 by studying its effect in mutants of aak-1;aak-2/AMP-activated kinase, sir-2.1/sirtuin, rsks-1/S6 kinase and daf-16/FOXO. We found that this compound was still effective increasing lifespan in all these mutants, indicating that these pathways are not involved in the effect. We have then monitored pharynx cytosolic and mitochondrial Ca2+ signalling and our results suggest that CGP37157 is probably inhibiting not only the mitochondrial Na+/Ca2+ exchanger, but also Ca2+ entry through the plasma membrane. Finally, a transcriptomic study detected that CGP37157 induced changes in lipid metabolism enzymes and a four-fold increase in the expression of ncx-6, one of the C. elegans mitochondrial Na+/Ca2+ exchangers. In summary, CGP37157 increases both lifespan and healthspan by a mechanism involving changes in cytosolic and mitochondrial Ca2+ homeostasis. Thus, Ca2+ signalling could be a promising target to act on aging.
Oleate Prevents Palmitate-Induced Mitochondrial Dysfunction in Chondrocytes
Authors: Vázquez-Mosquera Maria Eugenia , Fernández-Moreno Mercedes , Cortés-Pereira Estefanía , Relaño Sara , Dalmao-Fernández Andrea , Ramos-Louro Paula , Durán Sotuela Alejandro , Rego-Pérez Ignacio , Blanco Francisco J.
Published: June 2021

The association between obesity and osteoarthritis (OA) in joints not subjected to mechanical overload, together with the relationship between OA and metabolic syndrome, suggests that there are systemic factors related to metabolic disorders that are involved in the metabolic phenotype of OA. The aim of this work is study the effects of palmitate and oleate on cellular metabolism in an “in vitro” model of human chondrocytes. The TC28a2 chondrocyte cell line was used to analyze the effect of palmitate and oleate on mitochondrial and glycolytic function, Adenosine triphosphate (ATP) production and lipid droplets accumulation. Palmitate, but not oleate, produces mitochondrial dysfunction observed with a lower coupling efficiency, maximal respiration and spare respiratory capacity. Glycolytic function showed lower rates both glycolytic capacity and glycolytic reserve when cells were incubated with fatty acids (FAs). The production rate of total and mitochondrial ATP showed lower values in chondrocytes incubated with palmitic acid (PA). The formation of lipid droplets increased in FA conditions, being significantly higher when the cells were incubated with oleic acid (OL). These results may help explain, at least in part, the close relationship of metabolic pathologies with OA, as well as help to elucidate some of the factors that can define a metabolic phenotype in OA.
Identification of Small RNAs During High Light Acclimation in Arabidopsis thaliana
Authors: Tiwari Bhavika , Habermann Kristin , Arif M. Asif , Top Oguz , Frank Wolfgang
Published: June 2021

The biological significance of non-coding RNAs (ncRNAs) has been firmly established to be important for the regulation of genes involved in stress acclimation. Light plays an important role for the growth of plants providing the energy for photosynthesis; however, excessive light conditions can also cause substantial defects. Small RNAs (sRNAs) are a class of non-coding RNAs that regulate transcript levels of protein-coding genes and mediate epigenetic silencing. Next generation sequencing facilitates the identification of small non-coding RNA classes such as miRNAs (microRNAs) and small-interfering RNAs (siRNAs), and long non-coding RNAs (lncRNAs), but changes in the ncRNA transcriptome in response to high light are poorly understood. We subjected Arabidopsis plants to high light conditions and performed a temporal in-depth study of the transcriptome data after 3 h, 6 h, and 2 days of high light treatment. We identified a large number of high light responsive miRNAs and sRNAs derived from NAT gene pairs, lncRNAs and TAS transcripts. We performed target predictions for differentially expressed miRNAs and correlated their expression levels through mRNA sequencing data. GO analysis of the targets revealed an overrepresentation of genes involved in transcriptional regulation. In A. thaliana, sRNA-mediated regulation of gene expression in response to high light treatment is mainly carried out by miRNAs and sRNAs derived from NAT gene pairs, and from lncRNAs. This study provides a deeper understanding of sRNA-dependent regulatory networks in high light acclimation.
Development of DNA Markers From Physically Mapped Loci in Aegilops comosa and Aegilops umbellulata Using Single-Gene FISH and Chromosome Sequences
Authors: Said Mahmoud , Holušová Katerina , Farkas András , Ivanizs László , Gaál Eszter , Cápal Petr , Abrouk Michael , Martis-Thiele Mihaela M. , Kalapos Balázs , Bartoš Jan , Friebe Bernd , Doležel Jaroslav , Molnár István
Published: June 2021

Breeding of agricultural crops adapted to climate change and resistant to diseases and pests is hindered by a limited gene pool because of domestication and thousands of years of human selection. One way to increase genetic variation is chromosome-mediated gene transfer from wild relatives by cross hybridization. In the case of wheat (Triticum aestivum), the species of genus Aegilops are a particularly attractive source of new genes and alleles. However, during the evolution of the Aegilops and Triticum genera, diversification of the D-genome lineage resulted in the formation of diploid C, M, and U genomes of Aegilops. The extent of structural genome alterations, which accompanied their evolution and speciation, and the shortage of molecular tools to detect Aegilops chromatin hamper gene transfer into wheat. To investigate the chromosome structure and help develop molecular markers with a known physical position that could improve the efficiency of the selection of desired introgressions, we developed single-gene fluorescence in situ hybridization (FISH) maps for M- and U-genome progenitors, Aegilops comosa and Aegilops umbellulata, respectively. Forty-three ortholog genes were located on 47 loci in Ae. comosa and on 52 loci in Ae. umbellulata using wheat cDNA probes. The results obtained showed that M-genome chromosomes preserved collinearity with those of wheat, excluding 2 and 6M containing an intrachromosomal rearrangement and paracentric inversion of 6ML, respectively. While Ae. umbellulata chromosomes 1, 3, and 5U maintained collinearity with wheat, structural reorganizations in 2, 4, 6, and 7U suggested a similarity with the C genome of Aegilops markgrafii. To develop molecular markers with exact physical positions on chromosomes of Aegilops, the single-gene FISH data were validated in silico using DNA sequence assemblies from flow-sorted M- and U-genome chromosomes. The sequence similarity search of cDNA sequences confirmed 44 out of the 47 single-gene loci in Ae. comosa and 40 of the 52 map positions in Ae. umbellulata. Polymorphic regions, thus, identified enabled the development of molecular markers, which were PCR validated using wheat-Aegilops disomic chromosome addition lines. The single-gene FISH-based approach allowed the development of PCR markers specific for cytogenetically mapped positions on Aegilops chromosomes, substituting as yet unavailable segregating map. The new knowledge and resources will support the efforts for the introgression of Aegilops genes into wheat and their cloning.
Allelopathic, Phytotoxic, and Insecticidal Effects of Thymus proximus Serg. Essential Oil and Its Major Constituents
Authors: Zhou Shixing , Han Caixia , Zhang Chenpeng , Kuchkarova Nigora , Wei Caixia , Zhang Chi , Shao Hua
Published: June 2021

The chemical profile of Thymus proximus essential oil (EO) and its allelopathic, phytotoxic, and insecticidal activity was evaluated. Carvacrol, p-cymene, and γ-terpinene were detected as the major components of the EO, representing 85.9% of the total oil. About 50 g fresh plant material of T. proximus in a 1.5-L air tight container completely inhibited the seed germination of Amaranthus retroflexus and Poa anuua. Meanwhile, the EO exhibited potent phytotoxic activity, which resulted in 100% germination failure of both the test species when 2 mg/ml (for A. retroflexus) and 5 mg/ml (for Poa annua) oil was applied. The EO also triggered a significant insecticidal activity on Aphis gossypii with a LC50 value of 6.34 ppm. Carvacrol was identified as the main active compound responsible for both the plant suppressing effect and the insecticidal activity of the EO. Our study is the first on the allelopathic, phytotoxic, and insecticidal activity of T. proximus EO, and the determination of the responsible compound, which indicated their potential of being further explored as environment friendly biopesticides.
The Strengths Use Scale: Psychometric Properties, Longitudinal Invariance and Criterion Validity
Authors: van Zyl Llewellyn E. , Arijs Diane , Cole Matthew L. , Gliíska-Newes Aldona , Roll Lara C. , Rothmann Sebastiaan , Shankland Rebecca , Stavros Jacqueline M. , Verger Nicolas B.
Published: June 2021

Strengths use is an essential personal resource to consider when designing higher-educational programs and interventions. Strengths use is associated with positive outcomes for both the student (e.g., study engagement) and the university (e.g., academic throughput/performance). The Strengths Use Scale (SUS) has become a popular psychometric instrument to measure strengths use in educational settings, yet its use has been subjected to limited psychometric scrutiny outside of the U.S. Further, its longitudinal stability has not yet been established. Given the wide use of this instrument, the goals of this study were to investigate (a) longitudinal factorial validity and the internal consistency of the scale, (b) its equivalence over time, and (c) criterion validity through its relationship with study engagement over time. Data were gathered at two-time points, 3 months apart, from a sample of students in the Netherlands (n= 360). Longitudinal confirmatory factor analyses showed support for a two-factor model for overall strengths use, comprised ofAffinity for StrengthsandStrengths Use Behaviors. The SUS demonstrated high levels of internal consistency at both the lower- and upper bound limits at both time points. Further, strict longitudinal measurement invariance was established, which confirmed the instrument's temporal stability. Finally, criterion validity was established through relating strengths use to study engagement at different time stamps. These findings support the use of the SUS in practice to measure strengths use and to track the effectiveness of strengths use interventions within the higher education sector.