bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhanced nitrogen removal via Yarrowia lipolytica-mediated nitrogen and related metabolism of Chlorella pyrenoidosa from wastewater
Authors: Zhong Yuming , Lin Danni , Li Sufen , Wang Qin , Liu Hui , Ma Lukai , Liu Huifan
Published: June 2023

We investigated the optimum co-culture ratio with the highest biological nitrogen removal rate, revealing that chemical oxygen demand, total nitrogen (TN), and ammoniacal nitrogen (NH3-N) removal was increased in the Chlorella pyrenoidosa and Yarrowia lipolytica co-culture system at a 3:1 ratio. Compared with the control, TN and NH3-N content in the co-incubated system was decreased within 2–6 days. We investigated mRNA/microRNA (miRNA) expression in the C. pyrenoidosa and Y. lipolytica co-culture after 3 and 5 days, identifying 9885 and 3976 differentially expressed genes (DEGs), respectively. Sixty-five DEGs were associated with Y. lipolytica nitrogen, amino acid, photosynthetic, and carbon metabolism after 3 days. Eleven differentially expressed miRNAs were discovered after 3 days, of which two were differentially expressed and their target mRNA expressions negatively correlated with each other. One of these miRNAs regulates gene expression of cysteine dioxygenase, hypothetical protein, and histone-lysine N-methyltransferase SETD1, thereby reducing amino acid metabolic capacity; the other miRNA may promote upregulation of genes encoding the ATP-binding cassette, subfamily C (CFTR/MRP), member 10 (ABCC10), thereby promoting nitrogen and carbon transport in C. pyrenoidosa. These miRNAs may further contribute to the activation of target mRNAs. miRNA/mRNA expression profiles confirmed the synergistic effects of a co-culture system on pollutant disposal.
Nanofibers with homogeneous heparin distribution and protracted release profile for vascular tissue engineering
Authors: Zhang Hongmei , Zhang Qilu , Du Juan , Zhu Tonghe , Chen Dian , Liu Feiying , Dong Yang
Published: June 2023

In clinic, controlling acute coagulation after small-diameter vessel grafts transplantation is considered a primary problem. The combination of heparin with high anticoagulant efficiency and polyurethane fiber with good compliance is a good choice for vascular materials. However, blending water-soluble heparin with fat-soluble poly (ester-ether-urethane) urea elastomer (PEEUU) uniformly and preparing nanofibers tubular grafts with uniform morphology is a huge challenge. In this research, we have compounded PEEUU with optimized constant concentration of heparin by homogeneous emulsion blending, then spun into the hybrid PEEUU/heparin nanofibers tubular graft (H-PHNF) for replacing rats’ abdominal aorta in situ for comprehensive performance evaluation. The in vitro results demonstrated that H-PHNF was of uniform microstructure, moderate wettability, matched mechanical properties, reliable cytocompatibility, and strongest ability to promote endothelial growth. Replacement of resected abdominal artery with the H-PHNF in rat showed that the graft was capable of homogeneous hybrid heparin and significantly promoted the stabilization of vascular smooth muscle cells (VSMCs) as well as stabilizing the blood microenvironment. This research demonstrates the H-PHNF with substantial patency, indicating their potential for vascular tissue engineering.
The neuromodulatory effects of flavonoids and gut Microbiota through the gut-brain axis
Authors: Wang Haoran , Zhao Tingting , Liu Zhenjiang , Danzengquzhen  , Cisangzhuoma  , Ma Jinying , Li Xin , Huang Xiaodan , Li Bin
Published: June 2023

Recent investigations show that dietary consumption of flavonoids could potentially confer neuroprotective effects through a variety of direct and indirect mechanisms. Numerous flavonoids have been shown to cross the BBB and accumulate within the central nervous system (CNS). Some of these compounds purportedly counteract the accumulation and deleterious effects of reactive oxygen species, fostering neuronal survival and proliferation by inhibiting neuroinflammatory and oxidative stress responses. Moreover, several studies suggest that gut microbiota may participate in regulating brain function and host behavior through the production and modulation of bioactive metabolites. Flavonoids may shape gut microbiota composition by acting as carbon substrates to promote the growth of beneficial bacteria that produce these neuroprotective metabolites, consequently antagonizing or suppressing potential pathogens. By influencing the microbiota-gut-brain axis through this selection process, flavonoids may indirectly improve brain health. This review examines the current state of research into the relationship between bioactive flavonoids, gut microbiota, and the gut-brain axis.
A retrospective analysis and systematic review of the areas of entertainment computing and persuasive technologies for health
Authors: Silva Paula Alexandra , Bermúdez i Badia Sergi , Cameirão Mónica S.
Published: June 2023

The areas of entertainment computing and persuasive technologies are interdisciplinary fields that have gained increasing attention in the last decades. Health is one of the domains that has leveraged the benefits of fun to improve the results of its technology-enabled interventions. Previous work has reviewed the area of health entertainment from many different perspectives; however, an integrative analysis across disciplines (health sciences and computer science and engineering) throughout the development and validation cycle of technologies in this domain is missing. Having such an in-depth retrospective analysis would shed light on how research on entertainment computing and persuasive technologies for health has evolved, acknowledging its contributions, recognizing its strengths and limitations, and, as a result, allowing for the definition of ways forward. This paper engages in an unprecedented systematic review of the work produced between 2004 and 2017 in this area. From an initial total of 10,350 retrieved results, a total of 1,307 full-texts were included in this review and were thoroughly examined to gain a retrospective understanding of the type of studies that have been produced. Among others, this systematic review reports on the trends, venues of publication, and the characteristics of the studies including methodologies, sample characteristics, study design, the type of solutions produced, the conditions and domains of application, and the purpose of the studies. Results show that there is a growing body of research in the area, with most studies being published in roughly the same venues, and where the lion's share of solutions fall into the area of health rehabilitation and motor conditions. With regards to the most addressed health domains, our review shows that most solutions produced are aimed at stroke and fitness, followed by balance training. Most studies (82.3%) are conducted with their target population, mostly adults (18–49 y), and are conducted either in the lab or in clinical settings. However, the median sample size of the studies has remained stable (N = 20) in the last decades. Regarding technology, 2D and 3D solutions are equally used, and most systems employ movement sensors and are single-user. Finally, only 21.4% of the studies are performed using validated instruments.
Transcatheter edge-to-edge-repair of functional mitral regurgitation induces significant remodeling of mitral annular geometry
Authors: Paukovitsch Michael , Felbel Dominik , Jandek Madeleine , Keßler Mirjam , Rottbauer Wolfgang , Markovic Sinisa , Groeger Matthias , Tadic Marijana , Schneider Leonhard Moritz
Published: June 2023

Background

Mitral annular alterations in the context of heart failure often lead to severe functional mitral regurgitation (FMR), which should be treated with transcatheter edge-to-edge repair (M-TEER) according to current guidelines. M-TEER's effects on mitral valve (MV) annular remodeling have not been well elucidated.

Methods

141 consecutive patients undergoing M-TEER for treatment of FMR were included in this investigation. Comprehensive intraprocedural transesophageal echocardiography was used to assess the acute effects of M-TEER on annular geometry.

Results

Average patient age was 76.2 ± 9.6 years and 46.1% were female patients. LV ejection fraction was reduced (37.0% ± 13.7%) and all patients had mitral regurgitation (MR) grade ≥III. M-TEER achieved optimal MR reduction (MR ≤ I) in 78.6% of patients. Mitral annular anterior-posterior diameters (A-Pd) were reduced by −6.2% ± 9.5% on average, whereas anterolateral-posteromedial diameters increased (3.7% ± 8.9%). Overall, a reduction in MV annular areas was observed (2D: −1.8% ± 13.1%; 3D: −2.7% ± 13.7%), which strongly correlated with A-Pd reduction (2D: r = 0.6, p < 0.01; 3D: r = 0.65, p < 0.01). Patients that achieved A-Pd reduction above the median (≥6.3%) showed significantly lower rates of the composite endpoint rehospitalization for heart failure or all-cause mortality than those with less A-Pd reduction (9.9% vs. 28.6%, p = 0.037, log-rank p = 0.039). Furthermore, patients reaching the composite endpoint had an increase in annular area (2D: 3.0% ± 15.4%; 3D: 1.9% ± 15.3%), whereas those not reaching the endpoint showed a decrease (2D: −2.7% ± 12.4%; 3D: −3.6% ± 13.3%), although residual MR after M-TEER was similar between these groups (p = 0.57). In multivariate Cox regression adjusted for baseline MR, A-Pd reduction ≥6.3% remained a significant predictor of the combined endpoint (OR: 0.35, 95% CI: 0.14–0.85, p = 0.02).

Conclusion

Our findings indicate that effects of M-TEER in FMR are not limited to MR reduction, but also have significant impact on annular geometry. Moreover, A-Pd reduction, which mediates annular remodeling, has a significant impact on clinical outcome independent of residual MR.
The effect of using different computational system modeling approaches on applying systems thinking
Authors: Eidin Emil , Bowers Jonathan , Damelin Dan , Krajcik Joe
Published: June 2023

This paper discusses the potential of two computational modeling approaches in moving students from simple linear causal reasoning to applying more complex aspects of systems thinking (ST) in explanations of scientific phenomena. While linear causal reasoning can help students understand some natural phenomena, it may not be sufficient for understanding more complex issues such as global warming and pandemics, which involve feedback, cyclic patterns, and equilibrium. In contrast, ST has shown promise as an approach for making sense of complex problems. To facilitate ST, computational modeling tools have been developed, but it is not clear to what extent different approaches promote specific aspects of ST and whether scaffolding such thinking should start with supporting students first in linear causal reasoning before moving to more complex causal dimensions. This study compares two computational modeling approaches, static equilibrium and system dynamics modeling, and their potential to engage students in applying ST aspects in their explanations of the evaporative cooling phenomenon. To make such a comparison we analyzed 10th grade chemistry students’ explanations of the phenomenon as they constructed and used both modeling approaches. The findings suggest that using a system dynamics approach prompts more complex reasoning aligning with ST aspects. However, some students remain resistant to the application of ST and continue to favor linear causal explanations with both modeling approaches. This study provides evidence for the potential of using system dynamics models in applying ST. In addition, the results raise questions about whether linear causal reasoning may serve as a scaffold for engaging students in more sophisticated types of reasoning.
Association of hemoglobin, albumin, lymphocyte, and platelet score with risk of cerebrovascular, cardiovascular, and all-cause mortality in the general population: results from the NHANES 1999-2018
Authors: Pan Hong , Lin Shasha
Published: June 2023

Background and aims

Cardiovascular and cerebrovascular disease (CCDs) contribute to leading causes of morbidity and mortality in the United States of America (USA). Hemoglobin, albumin, lymphocyte, and platelet (HALP) score, a simple and convenient indicator, could reflect the combination of inflammation and nutritional status. This study was undertaken to evaluate the associations between HALP score and risk of cardiovascular, cerebrovascular, and all-cause mortality in the general population from the National Health and Nutrition Examination Survey (NHANES) 1999–2018.

Methods

We identified 21,578 participants during the 1999-2018 cycles of the NHANES in this research. HALP score was calculated as hemoglobin (g/L) × albumin (g/L) × lymphocytes (/L)/platelets (/L). Outcomes were cerebrovascular, cardiovascular, and all-cause mortality determined by the NHANES-linked National Death Index record and followed until 31 December 2019. Survey-weighted Cox regression, restricted cubic spline analysis, and subgroup analysis were applied to investigate relationships between HALP score and risk of mortality.

Results

This cohort study comprised 49.2% male and 50.8% female, of which the median age was 47 years old. In multivariate survey-weighted Cox regression adjusting for all confounders, compared with participants with low HALP scores, participants with highest HALP score had a lower risk of all-cause mortality (adjusted HR:0.80, 95% CI: 0.73, 0.89, P < 0.0001) and cardiovascular mortality (adjusted HR:0.61, 95% CI: 0.50, 0.75, P < 0.0001), and mediate HALP score had the lowest risk of all-cause mortality (adjusted HR:0.68, 95% CI: 0.62, 0.75, P < 0.0001) and cardiovascular mortality (adjusted HR:0.60, 95% CI: 0.48, 0.75, P < 0.0001). Restricted cubic spline analysis showed a non-linear relationship between HALP score and cardiovascular and all-cause mortality (all P values <0.001).

Conclusion

HALP score was independently associated with risk of cardiovascular and all-cause mortality, but not cerebrovascular mortality.
Association between gut microbiota and primary ovarian insufficiency: a bidirectional two-sample Mendelian randomization study
Authors: Wang Jiahui , Luo Rong , Zhao Xia , Xia Di , Liu Yi , Shen Tao , Liang Yuanjiao
Published: June 2023

Background

Recent studies have indicated a potential correlation between intestinal bacteria and primary ovarian insufficiency (POI). However, the causal relationship between the gut microbiota (GM) and POI remains unclear.

Methods

A bidirectional two-sample Mendelian randomization (MR) study was conducted to investigate the relationship between the GM and POI. Data on the GM were based on the MiBioGen consortium's summary statistics from the most comprehensive genome-wide association study meta-analysis to date (n=13,266), and POI data were obtained from the R8 release of the FinnGen consortium, containing a total of 424 cases and 181,796 controls. A variety of analytical methods, including inverse variance weighting, maximum likelihood, MR-Egger, weighted median, and constrained maximum likelihood and model averaging and Bayesian information criterion, were utilized to explore the connection between the GM and POI. The Cochran's Q statistics were used to evaluate the heterogeneity of instrumental variables. The MR-Egger and MR-pleiotropy residual sum and outlier (PRESSO) methods were used to identify the horizontal pleiotropy of instrumental variables. The MR Steiger test was used to evaluate the strength of causal relationships. A reverse MR study was performed to investigate the causal relationship between POI and the targeted GMs which were indicated to have a causal relationship with POI in the forward MR evaluation.

Results

The inverse variance weighted analysis indicated that Eubacterium (hallii group) (odds ratio [OR]=0.49, 95% confidence interval [CI]: 0.26–0.9, P=0.022) and Eubacterium (ventriosum group) (OR=0.51, 95% CI: 0.27–0.97, P=0.04) had protective effects on POI, and Intestinibacter (OR=1.82, 95% CI: 1.04–3.2, P=0.037) and Terrisporobacter (OR=2.47, 95% CI: 1.14–5.36, P=0.022) had detrimental effects on POI. Results of the reverse MR analysis indicated that POI had no significant influence on the four GMs. No significant heterogeneity or horizontal pleiotropy was observed in the performance of the instrumental variables.

Conclusion

This bidirectional two-sample MR study revealed a causal link between Eubacterium (hallii group), Eubacterium (ventriosum group), Intestinibacter, and Terrisporobacter and POI. Additional clinical trials are needed to gain a clearer understanding of the beneficial or detrimental effects of the GMs on POI and their mechanisms of action.
The role of apelinergic system in metabolism and reproductive system in normal and pathological conditions: an overview
Authors: Mehri Keyvan , Hamidian Gholamreza , Zavvari Oskuye Zohreh , Nayebirad Sepehr , Farajdokht Fereshteh
Published: June 2023

Lifestyle changes have made metabolic disorders as one of the major threats to life. Growing evidence demonstrates that obesity and diabetes disrupt the reproductive system by affecting the gonads and the hypothalamus-pituitary-gonadal (HPG) axis. Apelin, an adipocytokine, and its receptor (APJ) are broadly expressed in the hypothalamus nuclei, such as paraventricular and supraoptic, where gonadotropin-releasing hormone (GnRH) is released, and all three lobes of the pituitary, indicating that apelin is involved in the control of reproductive function. Moreover, apelin affects food intake, insulin sensitivity, fluid homeostasis, and glucose and lipid metabolisms. This review outlined the physiological effects of the apelinergic system, the relationship between apelin and metabolic disorders such as diabetes and obesity, as well as the effect of apelin on the reproductive system in both gender. The apelin–APJ system can be considered a potential therapeutic target in the management of obesity-associated metabolic dysfunction and reproductive disorders.
Industry–university–research knowledge flow in energy subjects: evolution of network structure in collaborative photovoltaic innovations
Authors: Yan Wuyin , Liu Hui , Han Baijun
Published: June 2023

This data report collected photovoltaic patents under the Industry-University-Research (IUR) collaborative innovation perspective. The evolution of the collaborative innovation network from 2000 to 2019 was studied. The characteristics of patent holders and overall network characteristics was analysed based on Social Network Analysis (SNA), including network size and degree, network density, and network degree centrality. The SNA results show that the network size and degree have increased significantly over time. The network density has become increasingly sparse as PV technology has developed and the number of core network members has increased. Universities and research institutions is gradually shown its clustering role in leading innovations and discipline construction. H01L is the leading knowledge domains studied by the industry, university, and research institutions. F24J and F24S were the second most frequently involved knowledge domains in each stage. Furthermore, two noteworthy knowledge domains are H02J and H02S, which are related to control and regulation of power systems. This analysis provides insights into the energy subjects and knowledge domains within collaborative innovations and education.
Adaptive frequency deviation improvement using a voltage-controlled storage inverter in a weak distribution network with a high penetration level of stochastic photovoltaic power
Authors: Li Zhicheng , Chen Jinyu , Zhang Weijun , Chen Dawei , Zhang Shuling , Gao Tongtong , Zhang Wei , Wang Zhenxiong
Published: June 2023

With the rapid increase in the use of renewable energy sources, the strength of the power grid is reduced, which may lead to many weak distribution networks. The inertia of the weak distribution network decreases significantly, which leads to poor voltage quality. It means that the voltage and frequency are distorted and deviated. Battery storage can balance the frequent power disturbance and improve the frequency quality. However, it usually requires a central controller to dispatch the power in the current-controlled mode or respond natively with a fixed linear curve in voltage-controlled mode. The performance is poor when the power demand is in a wide range, which further deteriorates the frequency quality. To solve this problem, this paper proposes an adaptive frequency deviation improvement method for energy storage in the voltage-controlled mode. This method can change the power output characteristics of the storage inverter according to the magnitude and trend of power demand, where both frequency deviation and changing rate are used to shape the output power curve. A transfer function model for a voltage-controlled storage inverter is set up for theoretical analysis. Then, with the model, an adaptive frequency deviation improvement method is proposed with a fast response to power demand in a wide range. Finally, the results verify the effectiveness of the proposed method for frequency quality improvement with a high penetration level of stochastic photovoltaic power.
Drought characterization using different indices, theory of run and trend analysis in bilate river watershed, rift valley of Ethiopia
Authors: Burka Ashenafi , Biazin Birhanu , Bewket Woldeamlak
Published: June 2023

Droughts have become more powerful and frequent, affecting more people for longer periods than any other natural disaster, particularly in eastern Africa. The unprecedented climate change has increased the severity, duration, and frequency of droughts. The objectives of this study were to evaluate performances of different drought indices for spatiotemporal drought characterization in the Bilate river watershed that represents part of the rift valley drylands in Ethiopia. Historical data for 39 years (1981–2019) from seven stations were used for drought analyses using the following indices: Standardized Precipitation Index (SPI), Standardized Precipitation Evapotranspiration Index (SPEI), Reconnaissance Drought Index (RDI), enhanced Reconnaissance Drought Index (eRDI) with different time scale and Self-Calibrated Palmer Drought Severity Index (scPDSI). Among them, SPI, SPEI, RDI and eRDI with 6-month and 9-month time scales were found to be the best correlated drought indices to characterize the historical drought events. Then, using the selected drought indices, temporal drought analysis showed occurrence of major drought events in the years: 1984/85, 1999/2000, 2002/3, and 2009. Some of these years are well known as famine years in some parts of Ethiopia including the study area. The results revealed spatial variation the severity of drought with extreme droughts occurred in the southern part of the Bilate watershed. Application of the theory of run confirmed that the maximum severity and duration of drought were observed at the Bilate Tena station that is located in the southern part of the watershed; the most severe being observed on a 9-month scale during 1984/85. Hossana and Wulbareg stations showed the highest frequency of drought over the study period. The Mann-Kendal trend test statistics showed an increasing trend of drought conditions in the study watershed.
Implications of changing trends in hydroclimatic and water quality parameters on estuarine habitats in the Gulf Coastal Plain
Authors: Croteau Amanda C. , Gancel Haley N. , Gebremicael Tesfay G. , Caffrey Jane M. , Deitch Matthew J.
Published: June 2023

Florida’s low elevation and geographic location make it particularly vulnerable to climate change effects such as sea level rise, increased intensity and frequency of storm events, and altered precipitation. Climate change is expected to exacerbate hydrological cycling with potential widespread implications for estuarine habitats that thrive under specific salinity regimes. We used historical data from sites in the eastern Gulf Coastal Plain, USA to examine trends and trend variability of several climatic, hydrologic, and estuarine water quality variables which have implications on seagrass and oyster habitat extent in downstream estuarine environments. We analyzed temperature, precipitation, low-flow and high-flow metrics (including the highest or lowest daily, 7-day average, and 30-day average) for each season annually over the period 1985–2020. We also analyzed estuarine water clarity metrics and salinity within waterbody segments of four estuary systems within the study area. Hydroclimate results showed that temperature increased at most sites. While there was variation in streamflow, the overall trend was declining streamflow. Declining trends were observed in most water clarity metrics, indicating improved clarity, especially in winter. Salinity generally declined across the study area. While overall streamflow decreased, main river stems to the estuaries had increasing trends in maximum streamflow characteristics, likely contributing to the decrease in estuarine salinity across the region. These results indicate that trends in streamflow (both magnitude and timing) in the watershed affect downstream estuarine water quality. These results have important implications on seagrass and oyster restoration and management efforts in the region, indicating that it is important to understand changing climatic and hydrologic conditions and how they may impact the estuarine resources.
The transcriptome response of astronaut leukocytes to long missions aboard the International Space Station reveals immune modulation
Authors: Stratis Daniel , Trudel Guy , Rocheleau Lynda , Pelchat Martin , Laneuville Odette
Published: June 2023

Introduction

Spaceflight leads to the deconditioning of multiple body systems including the immune system. We sought to characterize the molecular response involved by capturing changes in leukocyte transcriptomes from astronauts transitioning to and from long-duration spaceflight.

Methods

Fourteen male and female astronauts with ~6-month- long missions aboard the International Space Station (ISS) had 10 blood samples collected throughout the three phases of the study: one pre-flight (PF), four in-flight (IF) while onboard the ISS, and five upon return to Earth (R). We measured gene expression through RNA sequencing of leukocytes and applied generalized linear modeling to assess differential expression across all 10 time points followed by the analysis of selected time points and functional enrichment of changing genes to identify shifts in biological processes.

Results

Our temporal analysis identified 276 differentially expressed transcripts grouped into two clusters (C) showing opposite profiles of expression with transitions to and from spaceflight: (C1) decrease-then-increase and (C2) increase-then-decrease. Both clusters converged toward average expression between ~2 and ~6 months in space. Further analysis of spaceflight transitions identified the decrease-then-increase pattern with most changes: 112 downregulated genes between PF and early spaceflight and 135 upregulated genes between late IF and R. Interestingly, 100 genes were both downregulated when reaching space and upregulated when landing on Earth. Functional enrichment at the transition to space related to immune suppression increased cell housekeeping functions and reduced cell proliferation. In contrast, egress to Earth is related to immune reactivation.

Conclusion

The leukocytes’ transcriptome changes describe rapid adaptations in response to entering space followed by opposite changes upon returning to Earth. These results shed light on immune modulation in space and highlight the major adaptive changes in cellular activity engaged to adapt to extreme environments.
Gene set enrichment analysis identifies immune subtypes of kidney renal clear cell carcinoma with significantly different molecular and clinical properties
Authors: Chen Zuobing , Cao Wenxiu , Luo Jiangti , Abdelrahman Zeinab , Lu Qiqi , Wang Huafen , Wang Xiaosheng
Published: June 2023

Background

Kidney renal clear cell carcinoma (KIRC) is the most prevalent renal malignancy, marked by a high abundance of tumor-infiltrating lymphocytes (TILs) and an unfavorable prognosis upon metastasis. Numerous studies have demonstrated that KIRC possesses a tumor microenvironment that is highly heterogeneous, and this is associated with significant variations in the effectiveness of most first-line drugs administered to KIRC patients. Therefore, it is crucial to classify KIRC based on the tumor microenvironment, although these subtyping techniques are still inadequate.

Methods

By applying gene set enrichment scores of 28 immune signatures, we conducted a hierarchical clustering of KIRC and determined its immune subtypes. In addition, we conducted a comprehensive exploration of the molecular and clinical features of these subtypes, including survival prognosis, proliferation, stemness, angiogenesis, tumor microenvironment, genome instability, intratumor heterogeneity, and pathway enrichment.

Results

Through cluster analysis, two immune subtypes of KIRC were identified and termed Immunity-High (Immunity-H) and Immunity-Low (Immunity-L). This clustering outcome was consistent in four independent KIRC cohorts. The subtype Immunity-H exhibited elevated levels of TILs, tumor aneuploidy, homologous recombination deficiency, stemness, and proliferation potential, along with a poorer prognosis for survival. Despite this, the Immunity-L subtype demonstrated elevated intratumor heterogeneity and a stronger angiogenesis signature in contrast to Immunity-H. According to the results of pathway enrichment analysis, the Immunity-H subtype was found to be highly enriched in immunological, oncogenic, and metabolic pathways, whereas the Immunity-L subtype was highly enriched in angiogenic, neuroactive ligand-receptor interaction, and PPAR pathways.

Conclusions

Based on the enrichment of immune signatures in the tumor microenvironment, KIRC can be categorized into two immune subtypes. The two subtypes demonstrate considerably distinct molecular and clinical features. In KIRC, an increase in immune infiltration is linked to a poor prognosis. Patients with Immunity-H KIRC may exhibit active responses to PPAR and immune checkpoint inhibitors, whereas patients with Immunity-L may manifest favorable responses to anti-angiogenic agents and immune checkpoint inhibitors. The immunological classification provides molecular insights into KIRC immunity, as well as clinical implications for the management of this disease.
γδ T cells in immunotherapies for B-cell malignancies
Authors: Rimailho Léa , Faria Carla , Domagala Marcin , Laurent Camille , Bezombes Christine , Poupot Mary
Published: June 2023

Despite the advancements in therapy for B cell malignancies and the increase in long–term survival of patients, almost half of them lead to relapse. Combinations of chemotherapy and monoclonal antibodies such as anti-CD20 leads to mixed outcomes. Recent developments in immune cell-based therapies are showing many encouraging results. γδ T cells, with their potential of functional plasticity and their anti-tumoral properties, emerged as good candidates for cancer immunotherapies. The representation and the diversity of γδ T cells in tissues and in the blood, in physiological conditions or in B-cell malignancies such as B cell lymphoma, chronic lymphoblastic leukemia or multiple myeloma, provides the possibility to manipulate them with immunotherapeutic approaches for these patients. In this review, we summarized several strategies based on the activation and tumor-targeting of γδ T cells, optimization of expansion protocols, and development of gene-modified γδ T cells, using combinations of antibodies and therapeutic drugs and adoptive cell therapy with autologous or allogenic γδ T cells following potential genetic modifications.
Approaching hemophagocytic lymphohistiocytosis
Authors: Chinnici Aurora , Beneforti Linda , Pegoraro Francesco , Trambusti Irene , Tondo Annalisa , Favre Claudio , Coniglio Maria Luisa , Sieni Elena
Published: June 2023

Hemophagocytic Lymphohistiocytosis (HLH) is a rare clinical condition characterized by sustained but ineffective immune system activation, leading to severe and systemic hyperinflammation. It may occur as a genetic or sporadic condition, often triggered by an infection. The multifaceted pathogenesis results in a wide range of non-specific signs and symptoms, hampering early recognition. Despite a great improvement in terms of survival in the last decades, a considerable proportion of patients with HLH still die from progressive disease. Thus, prompt diagnosis and treatment are crucial for survival. Faced with the complexity and the heterogeneity of syndrome, expert consultation is recommended to correctly interpret clinical, functional and genetic findings and address therapeutic decisions. Cytofluorimetric and genetic analysis should be performed in reference laboratories. Genetic analysis is mandatory to confirm familial hemophagocytic lymphohistiocytosis (FHL) and Next Generation Sequencing is increasingly adopted to extend the spectrum of genetic predisposition to HLH, though its results should be critically discussed with specialists. In this review, we critically revise the reported laboratory tools for the diagnosis of HLH, in order to outline a comprehensive and widely available workup that allows to reduce the time between the clinical suspicion of HLH and its final diagnosis.
Limits to fishing: the case for collective self-limitation illustrated with an example of small-scale fisheries in Catalonia
Authors: Nogué-Algueró Borja , Kallis Giorgos , Ortega Miquel
Published: June 2023

Is there a limit to the amount of fish that can be taken from the sea? This question echoes the concern of the broader environmental movement in asking: are there ‘limits to growth’? If the answer is ‘yes’, then what must be done to remain within sustainable limits? Fifty years after the publication of the landmark reportLimits to Growth, new theories about limits highlight the importance of collective self-limitation, also in the context of fisheries management, in place of external, top-down determination and imposition of limits. This paper considers the shift in fisheries governance from regulating and establishing Maximum Sustainable Yields to collectively co-managing territories and ecosystems as symptomatic of a general turn from externally-imposed to self-imposed limitations. We show how perceptions and practices of limits are changing based on an ethnographic study of six small-scale fisheries co-management plans located off the Catalan coast in the Northwestern Mediterranean. The study evidences the challenges fishers face in attempting to define the limits of their agency to manage external forces that are often beyond their control. It concludes by arguing for the adoption of an ethos of collective self-limitation in fisheries governance to protect and benefit local communities and their environments.
Severe ocular complications of SJS/TEN and associations among pre-onset, acute, and chronic factors: a report from the international ophthalmology collaborative group
Authors: Ueta Mayumi , Inoue Chikara , Nakata Mitsuko , Sotozono Chie , Kim Mee Kum , Wakamatsu Tais , Jongkhajornpong Passara , Saeed Hajirah , Rauz Saaeha , Ma David Hui-Kang , Yoon Kyung Chul , Puangsricharern Vilavun , Bouchard Charles , Ahmad Sajjad , Seo Kyoung Yul , Joo Choun-Ki , Gomes Jose Alvaro Pereira , Chodosh James , Kinoshita Shigeru , Teramukai Satoshi
Published: June 2023

We formed an international research collaboration that included Japan, South Korea, Brazil, Thailand, Taiwan, the UK, and the US (682 patients from 13 hospitals between 2005 and 2020), to better evaluate the role of race, ethnicity, and other risk factors in the pathophysiology of Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Ophthalmologists often see SJS/TEN patients with severe ocular complications (SOC; frequency 50% SJS/TEN patients) when the patients are referred to them in the chronic stage after the acute stage has passed. Global data were collected using a Clinical Report Form, capturing pre-onset factors, as well as acute and chronic ocular findings. Key conclusions of this retrospective observational cohort study were as follows: (1) Ingestion of cold medications [acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs)] was significantly and positively correlated with trichiasis, symblepharon, and/or conjunctivalization of the cornea in the chronic stage; (2) common cold symptoms prior to onset of SJS/TEN were significantly and positively correlated with acute conjunctivitis and ocular surface erosions in the acute stage and with trichiasis and symblepharon and/or conjunctivalization of the cornea in the chronic stage; (3) patients with SJS/TEN who presented with SOC tended to be female; (4) patients less than 30 years of age are more likely to develop SOC in the acute and chronic stages of SJS/TEN; (5) patients with acute severe conjunctivitis with ocular surface erosion and pseudomembrane formation in the acute stage are more likely to develop ocular sequelae in the chronic stage; and (6) onychopathy in the acute stage was positively correlated with ocular sequelae in the chronic stage. Our findings show that the ingestion of cold medications, common cold symptoms prior to the onset of SJS/TEN, and a young age might strongly contribute to developing the SOC of SJS/TEN.
The neutrophil-to-lymphocyte ratio and lactate dehydrogenase combined in predicting liver metastasis and prognosis of colorectal cancer
Authors: Chen Qin , Li Guo-lin , Zhu Hong-quan , Yu Jian-Dong , Chen Zhi-Ping , Wu Jia-Yan , Lin Ze-Yu , Wan Yun-Le
Published: June 2023

Background

The neutrophil-to-lymphocyte ratio (NLR) and lactate dehydrogenase (LDH) level are inflammatory markers related to tumor growth and metabolism. This study investigated the value of preoperative NLR, LDH and the combination of NLR and LDH (NLR-LDH) for predicting colorectal cancer liver metastasis (CRLM) and tumor prognosis in the early stages of colorectal cancer (CRC).

Materials and methods

Three hundred patients undergoing CRC resection were included. Logistic regression analysis was used to estimate the correlation between CRLM time and inflammatory markers, and Kaplan–Meier survival and Cox regression analyses were used to estimate overall survival (OS). Forest plots were prepared based on the multivariate Cox analysis model and evaluated by receiver operating characteristic (ROC) curve analysis.

Results

The NLR cut-off value was 2.071 according to the ROC curve. The multivariate analysis showed that the elevated LDH level and a high NLR-LDH level were independent predictors of synchronous CRLM and OS (p < 0.05). The combination of a high NLR and elevated LDH and NLR-LDH levels suggested a poor prognosis and a significantly shorter median survival time than a low NLR and low levels of LDH and NLR-LDH. The ROC curve analysis results illustrated that the predictive value of the NLR-LDH score for synchronous CRLM [area under the curve (AUC) = 0.623, p < 0.001] and OS (AUC = 0.614, p = 0.001) was superior to that of the NLR or LDH score used alone.

Conclusion

LDH and NLR-LDH are reliable, easy-to-use, independent biomarkers for predicting synchronous or metachronous CRLM and OS in CRC patients. The NLR is an important monitoring index for CRLM. Preoperative NLR, LDH and NLR-LDH may help to guide the use of therapeutic strategies and cancer surveillance.
Distribution of drug-resistant genes in alveolar lavage fluid from patients with psittacosis and traceability analysis of causative organisms
Authors: Lu Huiqun , Yuan Jing , Wu Zeming , Wang Lingwei , Wu Shuang , Chen Qiongcheng , Zhang Zhen , Chen Zhigao , Zou Xuan , Hu Qinghua , Feng Tiejian , Lu Jianhua , Ji Liyin , Qiu Shuxiang , Xu Shiqin , Jiang Min , Li Yinghui , Peng Bo , Bai Qinqin , Cai Rui , Geng Yijie , Shi Xiaolu
Published: June 2023

Background

Chlamydia psittaci is a small bacterium often found in birds, including poultry, and domesticated mammals, which causes psittacosis (or parrot fever) in humans. Different strains of C. psittaci respond variably to antibiotics, suggesting a possible risk of antibiotic resistance. In general, different genotypes of C. psittaci have relatively stable hosts and different pathogenicity.

Methods

Macrogenomic sequencing was performed using nucleic acids extracted from psittacosis patients’ alveolar lavage fluid samples and analyzed for genetic variability and antibiotic resistance genes. Nucleic acid amplification sequences specific to the core coding region of the C. psittaci ompA gene were used, and a phylogenetic tree was constructed with C. psittaci genotypic sequences from other sources, including Chinese published sources. The C. psittaci found in each patient were genotyped by comparing ompA gene sequences. In addition, to better illustrate the relationship between genotype and host of C. psittaci, 60 bird fecal samples were collected from bird-selling stores for screening and C. psittaci typing.

Results

Macrogenomic sequence alignment revealed the presence of resistance genes in varying abundance in samples from all three patients, including C. psittaci resistance gene sequences from two patients that matched those previously published on NCBI. Based on ompA genotyping, two patients were infected with C. psittaci genotype A and one patient was infected with genotype B. All five C. psittaci-positive samples obtained from bird-selling stores were genotype A. Both genotypes are reported to be infectious to humans. The host origin of the samples and the previously reported main sources of each genotype suggested that all but one of the C. psittaci genotype A in this study were derived from parrots, while genotype B was probably derived from chickens.

Conclusion

The presence of bacterial resistance genes in psittacosis patients may affect the efficacy of clinical antibiotic therapy. Focusing on the developmental progression of bacterial resistance genes and differences in the therapeutic efficacy may facilitate effective treatment of clinical bacterial infections. Pathogenicity genotypes (e.g., genotype A and genotype B) are not limited to one animal host, suggesting that monitoring the development and changes of C. psittaci may help prevent transmission to humans.
Generation of a monoclonal antibody against duck circovirus capsid protein and its potential application for native viral antigen detection
Authors: Li Jinxin , Liu Fengli , Ren Zhihao , Fu Guanghua , Shi Jizhen , Zhao Naiyu , Huang Yu , Su Jingliang
Published: June 2023

Introduction

Duck circovirus (DuCV) infection is currently recognized as an important immunosuppressive disease in commercial duck flocks in China. Specific antibodies against DuCV viral proteins are required to improve diagnostic assays and understand the pathogenesis of DuCV infection.

Methods and results

To generate DuCV-specific monoclonal antibodies (mAbs), a recombinant DuCV capsid protein without the first 36 N-terminal amino acids was produced in Escherichia coli. Using the recombinant protein as an immunogen, a mAb was developed that reacted specifically with the DuCV capsid protein, expressed in E. coli and baculovirus systems. Using homology modeling and recombinant truncated capsid proteins, the antibody-binding epitope was mapped within the region of 144IDKDGQIV151, which is exposed to solvent in the virion capsid model structure. To assess the applicability of the mAb to probe the native virus antigen, the murine macrophage cell line RAW267.4 was tested for DuCV replicative permissiveness. Immunofluorescence and Western blot analysis revealed that the mAb recognized the virus in infected cells and the viral antigen in tissue samples collected from clinically infected ducks.

Discussion

This mAb, combined with the in vitro culturing method, would have widespread applications in diagnosing and investigating DuCV pathogenesis.
The correlation between the severity of cerebral microbleeds and serum HMGB1 levels and cognitive impairment in patients with cerebral small vessel disease
Authors: Wang Minghua , Liu Junli , Wang Fan , Li Qing , Zhang Jian , Ji Sibei , Li Shaomin , Lu Chengbiao , Zhao Jianhua
Published: June 2023

Objective

The study investigated the correlation and predictive value between the severity of cerebral microbleeds (CMBs) and the level of serum High Mobility Group Protein B1 (HMGB1) and the occurrence of cognitive impairment in patients with cerebral small vessel disease (CSVD).

Methods

A total of 139 patients with CSVD admitted to the Department of Neurology of the First Affiliated Hospital of Xinxiang Medical University from December 2020 to December 2022 were selected as study subjects. The Montreal Cognitive Assessment (MoCA) scale was used to assess the cognitive function and was divided into the cognitive impairment group and the cognitive normal group. Magnetic Resonance Imaging (MRI) and Susceptibility Weighted Imaging (SWI) were used to screen and assess the severity of CMBs. Serum HMGB1 levels of CSVD patients were measured by enzyme linked immunosorbent assay (ELISA). Multivariable logistic regression analysis was used to explore risk factors for cognitive impairment and CMBs. Pearson correlation analysis was used to investigate the correlation between HMGB1 and cognitive function. Receiver Operating Characteristics (ROC) curves were used to assess the predictive value of HMGB1 for the occurrence of cognitive impairment in patients with CMBs.

Results

High Mobility Group Protein B1, uric acid (UA), glycosylated hemoglobin (HbA1c), CMBs, lacunar cerebral infarction (LI), years of education, and history of hypertension were risk factors for cognitive impairment (P < 0.05); HMGB1 was significantly and negatively associated with total MoCA score, visuospatial/executive ability, and delayed recall ability (P < 0.05). HMGB1 was significantly and positively correlated with the number of CMBs (P < 0.05). The area under the ROC curve for HMGB1 predicting cognitive impairment in patients with CMBs was 0.807 (P < 0.001).

Conclusion

Serum HMGB1 levels are associated with the development of cognitive impairment in CSVD patients, and serum HMGB1 levels have a high predictive value for the development of cognitive impairment in CSVD patients with combined CMBs, which can be used for early clinical identification and intervention of vascular cognitive impairment.
Alzheimer’s disease: a mini-review for the clinician
Authors: Madnani Rishi S.
Published: June 2023

Alzheimer’s disease (AD), the most common form of dementia, is a striking example of the connection between neurophysiological abnormalities and higher-order cognitive deficiencies. Since its initial description in 1906, research into the pathophysiology and etiology of AD has led to the illumination of an incredibly complex set of genetic and molecular mechanisms for the disease’s progression, characterized by much more than the neuropathological hallmarks of beta-amyloid (Aβ) plaques and neurofibrillary tangles (NFTs). In this review, findings relating the neurodegeneration present in AD to its clinical presentation and treatment are summarized, with an emphasis on the interconnectedness of disease pathophysiology. Further, diagnostic guidelines are provided based on the National Institute on Aging-Alzheimer’s Association (NIA-AA) workgroup’s clinical recommendations. Through the dissemination of detailed but digestible open access resources such as this one, we can move towards an increase in the equity and accessibility of education for the modern clinician.