bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of simulated winter short photoperiods on the microbiome and intestinal metabolism in Huanghe carp (Cyprinus carpio haematopterus)
Authors: Wang Wenqian , Su Shengyan , Dong Ping , Feng Wenrong , Li Jianlin , Zhang Chengfeng , Tang Yongkai
Published: January 2024

Objective

As one of the most important environmental signals, photoperiod plays a crucial role in regulating the growth, metabolism, and survival of organisms. The photoperiod shifts with the transition of the seasons. The difference in photoperiod between summer and winter is the greatest under natural conditions. However, the effect of photoperiod on Huanghe carp (Cyprinus carpio haematopterus) was paid little attention. We investigated the impact of artificial manipulation of seasonal photoperiod on Huanghe carp by integrating growth performance, intestinal flora, and intestinal metabolome.

Method

We conducted an 8-week culture experiment with summer photoperiod (14 h light:10 h dark, n = 60) as the control group and winter photoperiod (10 h light:14 h dark, n = 60) based on the natural laws.

Results

Winter photoperiod provokes significant weight increases in Huanghe carp. The altered photoperiod contributed to a significant increase in triglyceride and low-density lipoprotein cholesterol levels and the gene expressions of lipid metabolism in the intestine of Huanghe carp. 16s rDNA sequencing revealed that winter photoperiod diminished intestinal flora diversity and altered the abundance. Specifically, the relative abundances of Fusobacteria and Acidobacteriota phyla were higher but Proteobacteria, Firmicutes, and Bacteroidetes phyla were reduced. Analogously, photoperiodic changes induced a significant reduction in the Pseudomonas, Vibrio, Ralstonia, Acinetobacter, and Pseudoalteromonas at the genus level. Additionally, metabolomics analysis showed more than 50% of differential metabolites were associated with phospholipids and inflammation. Microbiome and metabolome correlation analyses revealed that intestinal microbe mediated lipid metabolism alteration.

Conclusion

The winter photoperiod induced intestinal flora imbalance and lipid metabolism modification, ultimately affecting the growth of Huanghe carp. This study provides new insights into the effects of seasonal photoperiodic alteration on the well-being of fish.
Early rescue oocyte activation at 5 h post-ICSI is a useful strategy for avoiding unexpected fertilization failure and low fertilization in ICSI cycles
Authors: Xue Lintao , Wang Shikai , Wei Pingpin , Liu Haifang , Mao Xianbao , Qin Jie , Li Yaoxuan , Zhang Xiaohui , Li Zhengda , Huang Yueyue , Chen Liangshi , Shi Wen , Liu Liling
Published: January 2024

Introduction

Attempts to artificially activate unfertilized oocytes at 24 h post intracytoplasmic sperm injection (ICSI) have generally resulted in poor outcomes. This study aims to explore a new strategy for early judgement and rescue activation of unfertilized oocytes at 5 h post ICSI to avoid unexpected fertilization failure (UFF) or unexpected low fertilization (ULF) in ICSI cycles.

Methods

Firstly, time-lapse data from 278 ICSI cycles were retrospectively analyzed to establish an indicator for fertilization failure prediction. Secondly, 14 UFF and 20 ULF cycles were enrolled for an observational study, early rescue oocyte activation (EROA) was performed on oocytes without post-ICSI Pb2 extrusion to investigate fertilization efficiency, embryo development and clinical outcomes.

Results

The average time to Pb2 extrusion post-ICSI was 3.03±1.21 h, 95.54% of oocytes had extruded Pb2 before 5 h, and the sensitivity and specificity for monitoring Pb2 extrusion at 5 h by time-lapse imaging to predict fertilization were 99.59% and 99.78%, respectively. Early rescue activation of oocytes with no Pb2 extrusion resulted in acceptable fertilization and embryo developmental outcomes, in terms of the fertilization rate (75.00, 72.99%), 2PN fertilization rate (61.36, 56.93%), good-quality embryo rate (42.59, 50.00%), blastocyst formation rate (48.28, 46.03%), good-quality blastocyst rate (34.48, 33.33%), and oocyte utilization rate (36.36, 27.74%), for both UFF and ULF cycles. The clinical pregnancy, embryo implantation, and early miscarriage rates in the rescue oocyte activation group did not significantly differ from those in the Pb2 extrusion group. Fourteen unexpected fertilization failures and 20 low fertilization ICSI cycles were rescued and resulted in clinical pregnancy rates of 40.00% (4/10) and 57.14% (8/14), respectively.

Conclusions

This study demonstrates that monitoring Pb2 extrusion by time-lapse imaging can accurately predict fertilization outcomes, suggesting that early rescue oocyte activation at 5 h post ICSI is an effective strategy for avoiding unexpected fertilization failure and low fertilization in ICSI cycles.
Association of systemic immune-inflammation index with diabetic kidney disease in patients with type 2 diabetes: a cross-sectional study in Chinese population
Authors: Yan Pijun , Yang Yuxia , Zhang Xing , Zhang Yi , Li Jia , Wu Zujiao , Dan Xiaofang , Wu Xian , Chen Xiping , Li Shengxi , Xu Yong , Wan Qin
Published: January 2024

Objective

Systemic immune-inflammation index (SII), a novel inflammatory marker, has been reported to be associated with diabetic kidney disease (DKD) in the U.S., however, such a close relationship with DKD in other countries, including China, has not been never determined. We aimed to explore the association between SII and DKD in Chinese population.

Methods

A total of 1922 hospitalized patients with type 2 diabetes mellitus (T2DM) included in this cross-sectional study were divided into three groups based on estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (ACR): non-DKD group, DKD stages 1–2 Alb group, and DKD-non-Alb+DKD stage 3 Alb group. The possible association of SII with DKD was investigated by correlation and multivariate logistic regression analysis, and receiver-operating characteristic (ROC) curves analysis.

Results

Moving from the non-DKD group to the DKD-non-Alb+DKD stage 3 Alb group, SII level was gradually increased (P for trend <0.01). Partial correlation analysis revealed that SII was positively associated with urinary ACR and prevalence of DKD, and negatively with eGFR (all P<0.01). Multivariate logistic regression analysis showed that SII remained independently significantly associated with the presence of DKD after adjustment for all confounding factors [(odds ratio (OR), 2.735; 95% confidence interval (CI), 1.840-4.063; P < 0.01)]. Moreover, compared with subjects in the lowest quartile of SII (Q1), the fully adjusted OR for presence of DKD was 1.060 (95% CI 0.773-1.455) in Q2, 1.167 (95% CI 0.995-1.368) in Q3, 1.266 (95% CI 1.129-1.420) in the highest quartile (Q4) (P for trend <0.01). Similar results were observed in presence of DKD stages 1–2 Alb or presence of DKD-non- Alb+DKD stage 3 Alb among SII quartiles. Last, the analysis of ROC curves revealed that the best cutoff values for SII to predict DKD, Alb DKD stages 1- 2, and DKD-non-Alb+ DKD stage 3 Alb were 609.85 (sensitivity: 48.3%; specificity: 72.8%), 601.71 (sensitivity: 43.9%; specificity: 72.3%), and 589.27 (sensitivity: 61.1%; specificity: 71.1%), respectively.

Conclusion

Higher SII is independently associated with an increased risk of the presence and severity of DKD, and SII might be a promising biomarker for DKD and its distinct phenotypes in Chinese population.
An environmental perspective on developing dual energy storage for electric vehicles—a case study exploring Al-ion vs. supercapacitors alongside Li-ion
Authors: Melzack N. , Wills R. G. A. , Cruden A. J.
Published: January 2024

Much focus of dual energy-storage systems (DESSs) for electric vehicles (EVs) has been on cost reduction and performance enhancement. While these are important in the development of better systems, the environmental impacts of system and component-level choices should not be overlooked. The current interest in EVs is primarily motivated by environmental reasons such as climate change mitigation and reduction of fossil fuel use, so it is important to develop environmentally sound alternatives at the design stage. Assessing the environmental impact of developmental and mature chemistries provides valuable insights into the technologies that need to be selected now and which to develop for the future. This paper presents a cradle-to-gate (i.e., all raw material and production elements are considered; however, the “use” phase and recycling are not) lifecycle assessment of a DESS with Li-ion and aqueous Al-ion cells and that of one with Li-ion cells and supercapacitors. These are also compared to a full Li-ion EV battery in terms of their environmental impact for both a bus and car case study. Key findings show that the use of a DESS overall reduces the environmental impacts over the vehicle lifetime and provides an argument for further development of aqueous Al-ion cells for this application.
Identification of different lithofacies laminations in oil shale and their mechanical properties
Authors: Cheng Shizhong , Sheng Mao , Deng Chao
Published: January 2024

Lamination can greatly enhance the anisotropy and heterogeneity of shale and plays a significant role in influencing hydraulic fracturing. The structure and mechanical difference of different lithofacies lamination are the basis to reveal the fracture propagation mechanism. In this paper, research focused on three continental oil shale with different lithofacies in Qikou sag, Bohai Bay basin, including Quartz-Feldspar dominated shale, Carbonate dominated shale and mixed-mineral shale. Scanning electron microscopy and mineral analysis are used to identify quartz-feldspar lamination and mixture lamination in Quartz-Feldspar dominated shales, as well as carbonate lamination and mixture lamination in Carbonate dominated shales. The distinct laminations with different characteristics were precisely located using FIB, which served as the guiding tool for the indentation experiment. The micromechanical properties of laminations with different lithofacies in oil shale samples are examined using the nanoindentation technique, highlighting their distinct differences. The findings demonstrate that the micromechanical properties of quartz-feldspar lamination in Quartz-Feldspar dominated shales exhibit superior strength, while the mechanical difference between laminations in Quartz-Feldspar dominated shales are significantly larger. The quartz-feldspar lamination exhibits the highest resistance when subjected to indentation force. The mechanical properties of mixture lamination in Quartz-Feldspar dominated shales and Carbonate dominated shales are comparable due to their similar mineral composition. Moreover, in conjunction with macroscopic rock mechanics experiments, it has been verified that the lamination structure facilitates the initiation and propagation of macroscopic fractures under stress loading.
Research on the calculation method of the reasonable utilization rate of renewable energy considering generation–grid–load–storage coordinated planning
Authors: Liu Yongcheng , Jiang Zongnan , Sun Yalu , Yang Xi , Wang Xiang , Zhang Dehai
Published: January 2024

The continuous advancement of the dual carbon goal will lead to fundamental changes in China’s energy structure, with renewable energy emerging as the dominant force in the power supply system. As the proportion of installed capacity for renewable energy continues to increase, the absorption capacity and reasonable utilization rate of renewable energy will become a concern for all sectors of society. At present, the degree of utilization of renewable energy has emerged as a significant factor limiting the development of renewable energy sources. Due to variations in the power structure, load characteristics, and flexible adjustment resources across different regions, blindly pursuing full absorption or higher utilization of renewable energy as a goal can result in increased reserve costs for the system and limited economic benefits, and hinder the development of renewable energy. Therefore, the present study develops a generation–grid–load–storage collaborative planning model aimed at achieving economic optimization by setting different renewable energy utilization rates and obtains the installed capacity of renewable energy and storage under different conditions in the planned year of Gansu Province. The economic analysis indicates that the optimal utilization rate of renewable energy in Gansu Province is projected to decrease from 100% during the period of 2024–2028 to approximately 90% from 2040 to 2060. It serves as a valuable tool for informing the planning and economic development of renewable energy and storage initiatives in Gansu Province, facilitating the achievement of its dual-carbon objectives.
Influences of suction pipe structures on hydraulic performance and internal flow of electric coolant pumps
Authors: Yang Anlong , Gu Yandong , Cheng Li , Zhao Wenpeng
Published: January 2024

An electric coolant pump (ECP) serves as a critical component in the thermal management of electric vehicles. To fulfill the requirements of pressurizing and circulating coolant for various components, a complex structure with multiple pipes is integrated into the pump inlet. This study focuses on the design and analysis of three suction pipe structures: a straight pipe (Case A), a bend (Case B), and a combination of a bend with manifolds (Case C). The objective of this study is to explore the impacts of suction pipe structures on the hydraulic performance, flow pattern, temperature distribution, and vorticity of ECP. Taking into account the variability of coolant physical parameters with temperature, ECP is numerically simulated using the unsteady Reynolds-averaged Navier–Stokes (RANS) equation and the shear stress transport k–ω turbulence model. The experimental and numerical results exhibit good agreement. Case A demonstrates the highest efficiency, Case B follows as the second most efficient, and Case C displays the lowest efficiency. However, the pressure rise remains essentially consistent in all cases. The average efficiencies of Cases B and C are 1.18% and 2.13% lower than that of Case A. The temperature of ECP increases with an increase in the coolant temperature. The temperature of the printed circuit board (PCB) surpasses that of the motor. Case A exhibits the most favorable flow pattern, while Case C demonstrates the least favorable. The bend introduces secondary flow, further intensified by the manifold, leading to an increase in vorticity. The high-vorticity zones expand as the flow rate increases. This study offers valuable insights into the optimization of the ECP suction pipe structure.
Unraveling the impact of phytoplankton secretions on the behavior of metal-containing engineered nanoparticles in aquatic environment
Authors: Gasco Rocco , Slaveykova Vera I.
Published: January 2024

Based on the up-to-date knowledge we critically discuss the current understanding of the influence of the compounds secreted by phytoplankton species on the fate of metal-containing engineered nanoparticles (ENPs) in aquatic settings. Different biomolecules, such as extracellular polymeric substances (EPS) and exometabolites play important, yet to elucidate, role in the dissolution, colloidal stability, transformations and biouptake of the ENPs and thus shape their behavior within the phycosphere. Phytoplankton secretions can also mediate the synthesis of ENPs from dissolved ions by reducing the metals ions and capping the newly formed ENPs. However, the environmental significance of this process remains to be demonstrated. Exposure to ENPs triggers changes in the secretion of the biomolecules. An improved understanding of the regulatory mechanism and exometabolite changes due to ENP exposure is essential for deciphering the ENPs-phytoplankton interactions. Unveiling the significance of secreted biomolecules in modulating the behavior of the metal-containing ENPs is central for understudying the phytoplankton-ENPs feedbacks, drivers of transformations of ENPs and their mechanisms in the aquatic environment.
The effect of the oak powdery mildew, oak lace bug, and other foliofagous insects on the growth of young pedunculate oak trees
Authors: Marković Čedomir , Kanjevac Branko , Perišić Uroš , Dobrosavljević Jovan
Published: January 2024

Pedunculate oak (Quercus robur L., 1753) is one of the widely distributed oak species in Europe. A large number of organisms develop on its leaves. To determine the extent to which the oak powdery mildew, oak lace bug, and other foliofagous insects affect the growth of young oak trees, three experimental fields were selected in a 10-year-old pedunculate oak stand. In each of them, 50 trees were randomly selected, and their height was measured at the beginning of the vegetative season. The first experimental field was treated with a systemic insecticide, the second with a systemic fungicide, and the third, a comparison area, with water, during the entire vegetative season. At the end of the vegetative season, 25 plants with one apical branch were selected in each experimental field. Their height was measured, and 20 leaves were taken from each plant to determine the extent of the damage on them at the end of the experiment. After processing the obtained data, it was determined that: 1. Both foliofagous insects and oak leaf inhabiting fungi affect the growth of the oak trees significantly; 2. The oak lace bug did not influence the growth of the young trees significantly, as its abundance was low in all of the experimental areas; 3. The greatest damage on the leaves was caused by defoliator insects, which is why they contributed the most to the decrease in growth caused by insects; 4. The influence of the foliofagous insects on the growth of the trees was not significantly different from the influence of fungi; 5. Suppression of oak powdery mildew and foliofagous insects on young trees is useful as it positively influences the vitality and growth of those trees, and contributes to economic and ecological gain.
Dissecting cellular heterogeneity and intercellular communication in cholangiocarcinoma: implications for individualized therapeutic strategies
Authors: Zhou Zun-Qiang , Zhang Yi , Xu Zi-Yang , Tang Xiao-Li , Chen Xiao-Hua , Guan Jiao , Zhang Zheng-Yun
Published: January 2024

Background: Cholangiocarcinoma is characterized by significant cellular heterogeneity and complex intercellular communication, which contribute to its progression and therapeutic resistance. Therefore, unraveling this complexity is essential for the development of effective treatments.

Methods: We employed single-cell RNA sequencing (scRNA-seq) to investigate cellular heterogeneity and intercellular communication in cholangiocarcinoma and adjacent normal tissues from two patients. Distinct cell types were identified, and gene ontology analyses were conducted to determine enriched pathways. Moreover, cell-cell communications were analyzed using CellChat, a computational framework. Additionally, we performed sub-clustering analysis of T cells and fibroblasts.

Results: The scRNA-seq analysis revealed distinct cell clusters and diverse cellular compositions of cholangiocarcinoma. CellChat analysis underscored an amplified outgoing signal from fibroblasts within the tumor, suggesting their pivotal role in the tumor microenvironment. Furthermore, T cell sub-clustering analysis revealed an active immune response within the tumor and new tumor-specific T cell clonotypes, suggesting scope for targeted immunotherapies. Moreover, fibroblast sub-clustering analysis indicated distinct functional states and highlighted the role of activated fibroblasts in shaping intercellular communication, particularly via CD99 and FN1 signaling.

Conclusion: Our findings reveal the intricate cellular heterogeneity and dynamic intercellular communication in cholangiocarcinoma, providing valuable insights into disease progression and potential therapeutic strategies.
Placental cytochrome P450 methylomes in infants exposed to prenatal opioids: exploring the effects of neonatal opioid withdrawal syndrome on health horizons
Authors: Radhakrishna Uppala , Sadhasivam Senthilkumar , Radhakrishnan Rupa , Forray Ariadna , Muvvala Srinivas B. , Metpally Raghu P. , Patel Saumya , Rawal Rakesh M. , Vishweswaraiah Sangeetha , Bahado-Singh Ray O. , Nath Swapan K.
Published: January 2024

Background: Neonatal opioid withdrawal syndrome (NOWS), arises due to increased opioid use during pregnancy. Cytochrome P450 (CYP) enzymes play a pivotal role in metabolizing a wide range of substances in the human body, including opioids, other drugs, toxins, and endogenous compounds. The association between CYP gene methylation and opioid effects is unexplored and it could offer promising insights.

Objective: To investigate the impact of prenatal opioid exposure on disrupted CYPs in infants and their anticipated long-term clinical implications.

Study Design: DNA methylation levels of CYP genes were analyzed in a cohort of 96 placental tissues using Illumina Infinium MethylationEPIC (850 k) BeadChips. This involved three groups of placental tissues: 32 from mothers with infants exposed to opioids prenatally requiring pharmacologic treatment for NOWS, 32 from mothers with prenatally opioid-exposed infants not needing NOWS treatment, and 32 from unexposed control mothers.

Results: The study identified 20 significantly differentially methylated CpG sites associated with 17 distinct CYP genes, with 14 CpGs showing reduced methylation across 14 genes (CYP19A1, CYP1A2, CYP4V2, CYP1B1, CYP24A1, CYP26B1, CYP26C1, CYP2C18, CYP2C9, CYP2U1, CYP39A1, CYP2R1, CYP4Z1, CYP2D7P1 and), while 8 exhibited hypermethylation (CYP51A1, CYP26B1, CYP2R1, CYP2U1, CYP4X1, CYP1A2, CYP2W1, and CYP4V2). Genes such as CYP1A2, CYP26B1, CYP2R1, CYP2U1, and CYP4V2 exhibited both increased and decreased methylation. These genes are crucial for metabolizing eicosanoids, fatty acids, drugs, and diverse substances.

Conclusion: The study identified profound methylation changes in multiple CYP genes in the placental tissues relevant to NOWS. This suggests that disruption of DNA methylation patterns in CYP transcripts might play a role in NOWS and may serve as valuable biomarkers, suggesting a future pathway for personalized treatment. Further research is needed to confirm these findings and explore their potential for diagnosis and treatment.
Association between gut microbiota and glioblastoma: a Mendelian randomization study
Authors: Wang Song , Yin Fangxu , Guo Zheng , Li Rui , Sun Wei , Wang Yuchao , Geng Yichen , Sun Chao , Sun Daqing
Published: January 2024

Background: Glioblastoma (GBM) is the most prevalent malignant brain tumor, significantly impacting the physical and mental wellbeing of patients. Several studies have demonstrated a close association between gut microbiota and the development of GBM. In this investigation, Mendelian randomization (MR) was employed to rigorously evaluate the potential causal relationship between gut microbiota and GBM.

Methods: We utilized summary statistics derived from genome-wide association studies (GWAS) encompassing 211 gut microbiota and GBM. The causal association between gut microbiota and GBM was scrutinized using Inverse Variance Weighted (IVW), MR-Egger, and Weighted Median (WM) methods. Cochrane’s Q statistic was employed to conduct a heterogeneity test. MR-Pleiotropic Residuals and Outliers (MR-PRESSO) were applied to identify and eliminate SNPs with horizontal pleiotropic outliers. Additionally, Reverse MR was employed to assess the causal relationship between GBM and pertinent gut microbiota.

Results: The MR study estimates suggest that the nine gut microbiota remain stable, considering heterogeneity and sensitivity methods. Among these, the family.Peptostreptococcaceae and genus.Eubacterium brachy group were associated with an increased risk of GBM, whereas family.Ruminococcaceae, genus.Anaerostipes, genus.Faecalibacterium, genus.LachnospiraceaeUCG004, genus.Phascolarctobacterium, genus.Prevotella7, and genus.Streptococcus were associated with a reduced risk of GBM. Following Benjamini and Hochberg (BH) correction, family.Ruminococcaceae (OR = 0.04, 95% CI: 0.01–0.19, FDR = 0.003) was identified as playing a protective role against GBM.

Conclusion: This groundbreaking study is the first to demonstrate that family.Ruminococcaceae is significantly associated with a reduced risk of GBM. The modulation of family_Ruminococcaceae for the treatment of GBM holds considerable potential clinical significance.
Nanomedicine for cancer targeted therapy with autophagy regulation
Authors: He Ketai , Chen Mingkun , Liu Jiao , Du Shufang , Ren Changyu , Zhang Jifa
Published: January 2024

Nanoparticles have unique physical and chemical properties and are currently widely used in disease diagnosis, drug delivery, and new drug development in biomedicine. In recent years, the role of nanomedical technology in cancer treatment has become increasingly obvious. Autophagy is a multi-step degradation process in cells and an important pathway for material and energy recovery. It is closely related to the occurrence and development of cancer. Because nanomaterials are highly targeted and biosafe, they can be used as carriers to deliver autophagy regulators; in addition to their favorable physicochemical properties, nanomaterials can be employed to carry autophagy inhibitors, reducing the breakdown of chemotherapy drugs by cancer cells and thereby enhancing the drug’s efficacy. Furthermore, certain nanomaterials can induce autophagy, triggering oxidative stress-mediated autophagy enhancement and cell apoptosis, thus constraining the progression of cancer cells.There are various types of nanoparticles, including liposomes, micelles, polymers, metal-based materials, and carbon-based materials. The majority of clinically applicable drugs are liposomes, though other materials are currently undergoing continuous optimization. This review begins with the roles of autophagy in tumor treatment, and then focuses on the application of nanomaterials with autophagy-regulating functions in tumor treatment.
Microbial evasion of the complement system: a continuous and evolving story
Authors: Heggi Mariam T. , Nour El-Din Hanzada T. , Morsy Dina I. , Abdelaziz Noha I. , Attia Ahmed S.
Published: January 2024

The complement system is a fundamental part of the innate immune system that plays a key role in the battle of the human body against invading pathogens. Through its three pathways, represented by the classical, alternative, and lectin pathways, the complement system forms a tightly regulated network of soluble proteins, membrane-expressed receptors, and regulators with versatile protective and killing mechanisms. However, ingenious pathogens have developed strategies over the years to protect themselves from this complex part of the immune system. This review briefly discusses the sequence of the complement activation pathways. Then, we present a comprehensive updated overview of how the major four pathogenic groups, namely, bacteria, viruses, fungi, and parasites, control, modulate, and block the complement attacks at different steps of the complement cascade. We shed more light on the ability of those pathogens to deploy more than one mechanism to tackle the complement system in their path to establish infection within the human host.
Immunophenotype associated with high sustained antibody titers against enzyme replacement therapy in infantile-onset Pompe disease
Authors: Desai Ankit K. , Smith P. Brian , Yi John S. , Rosenberg Amy S. , Burt Trevor D. , Kishnani Priya S.
Published: January 2024

Introduction

The efficacy of enzyme replacement therapy (ERT) with alglucosidase alfa for infantile-onset Pompe disease (IOPD) is limited in some patients due to the development of high and sustained antibody titers (HSAT; ≥12,800).

Methods

We carried out detailed immunophenotyping of IOPD patients (n=40), including analysis of circulating cell populations by flow cytometry and plasma cytokines by multiplex array, to determine whether patients with HSAT have unique immunological characteristics compared to those with low titers (LT; <12,800).

Results

Compared to patients with LT, patients who develop HSAT were skewed toward a type 2 immune profile, with an increased frequency of Th2 cells that was positively correlated with levels of Th2 (IL-4, IL-5, IL-13) and pro-inflammatory (IL-6, TNF-α, MIP-1α, MIP-1β) cytokines. B cells were increased in HSAT patients with a decreased fraction of unswitched memory B cells. Plasma GM-CSF concentrations were lower on average in HSAT patients, while CXCL11 was elevated. Finally, using principal components analysis, we derived an HSAT Signature Score that successfully stratified patients according to their antibody titers.

Discussion

The immune profiles revealed in this study not only identify potential biomarkers of patients that developed HSAT but also provide insights into the pathophysiology of HSAT that will ultimately lead to improved immunotherapy strategies.
Changes in chemokine and growth factor levels may be useful biomarkers for monitoring disease severity in COVID-19 patients; a pilot study
Authors: Wolszczak-Biedrzycka Blanka , Dorf Justyna , Wojewódzka-Żelezniakowicz Marzena , Żendzian-Piotrowska Małgorzata , Dymicka-Piekarska Violetta , Matowicka-Karna Joanna , Maciejczyk Mateusz
Published: January 2024

Aim

The aim of the present study was to assess differences in the serum levels of chemokines and growth factors (GFs) between COVID-19 patients and healthy controls. The diagnostic utility of the analyzed proteins for monitoring the severity of the SARS-CoV- 2 infection based on the patients’ MEWS scores was also assessed.

Materials and methods

The serum levels of chemokines and growth factors were analyzed in hospitalized COVID-19 patients (50 women, 50 men) with the use of the Bio-Plex Pro™ Human Cytokine Screening Panel (Biorad) and the Bio-Plex Multiplex system.

Results

The study demonstrated that serum levels of MIP-1α, RANTES, Eotaxin, CTACK, GRO-α, IP-10, MIG, basic-FGF, HGF, SCGF-β, G-CSF, M-CSF, SCF, MIF, LIF, and TRAIL were significant higher in COVID-19 patients than in the control group. The concentrations of CTACK, GRO-α, IP-10, MIG, basic-FGF, HGF, PDGF- BB, GM-CSF, SCF, LIF, and TRAIL were higher in asymptomatic/mildly symptomatic COVID-19 patients (stage 1) and COVID-19 patients with pneumonia without respiratory failure (stage 2). The receiver operating characteristic (ROC) analysis revealed that IP-10, MIF, MIG, and basic-FGF differentiated patients with COVID-19 from healthy controls with the highest sensitivity and specificity, whereas GM-CSF, basic-FGF, and MIG differentiated asymptomatic/mildly symptomatic COVID-19 patients (stage 1) from COVID-19 patients with pneumonia without respiratory failure (stage 2) with the highest sensitivity and specificity.

Conclusions

MIG, basic-FGF, and GM-CSF can be useful biomarkers for monitoring disease severity in patients with COVID-19.
P2Y2-P2X7 receptors cross-talk in primed mesenteric endothelial cells upregulates NF-κB signaling favoring mononuclear cell adhesion in schistosomiasis
Authors: Oliveira Nathália Ferreira , Monteiro Matheus Macedo L. V. , Mainieri Nathália Santos , Tamura Augusto Shuiti , Pereira Letícia Massimo , Crepaldi Leticia Diniz , Coutinho-Silva Robson , Savio Luiz Eduardo Baggio , Silva Claudia Lucia Martins
Published: January 2024

Schistosomiasis is an intravascular infectious disease that impacts over 200 million people globally. In its chronic stage, it leads to mesenteric inflammation with significant involvement of monocytes/macrophages. Endothelial cells lining the vessel lumens play a crucial role, and mount of evidence links this disease to a downregulation of endoprotective cell signaling favoring a primed and proinflammatory endothelial cell phenotype and therefore the loss of immunovascular homeostasis. One hallmark of infectious and inflammatory conditions is the release of nucleotides into the extracellular milieu, which, in turn, act as innate messengers, activating purinergic receptors and triggering cell-to-cell communication. ATP influences the progression of various diseases through P2X and P2Y purinergic receptor subtypes. Among these receptors, P2Y2 (P2Y2R) and P2X7 (P2X7R) receptors stand out, known for their roles in inflammation. However, their specific role in schistosomiasis has remained largely unexplored. Therefore, we hypothesized that endothelial P2Y2R and P2X7R could contribute to monocyte adhesion to mesenteric endothelial cells in schistosomiasis. Using a preclinical murine model of schistosomiasis associated with endothelial dysfunction and age-matched control mice, we showed that endothelial P2Y2R and P2X7R activation increased monocyte adhesion to cultured primary endothelial cells in both groups. However, a distinct upregulation of endothelial P2Y2R-driven canonical Ca2+ signaling was observed in the infected group, amplifying adhesion. In the control group, the coactivation of endothelial P2Y2R and P2X7R did not alter the maximal monocyte adhesion induced by each receptor individually. However, in the infected group, this coactivation induced a distinct upregulation of P2Y2R-P2X7R-driven canonical signaling, IL-1β release, and VCAM-1 expression, with underlying mechanisms involving inflammasome and NF-κB signaling. Therefore, current data suggest that schistosomiasis alters endothelial cell P2Y2R/P2X7R signaling during inflammation. These discoveries advance our understanding of schistosomiasis. This intricate interplay, driven by PAMP-triggered endothelial P2Y2R/P2X7R cross-talk, emerges as a potential key player in the mesenteric inflammation during schistosomiasis.
Targeting HER3 to overcome EGFR TKI resistance in NSCLC
Authors: Chen Qiuqiang , Jia Gang , Zhang Xilin , Ma Wenxue
Published: January 2024

Receptor tyrosine kinases (RTKs) play a crucial role in cellular signaling and oncogenic progression. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) have become the standard treatment for advanced non-small cell lung cancer (NSCLC) patients with EGFR-sensitizing mutations, but resistance frequently emerges between 10 to 14 months. A significant factor in this resistance is the role of human EGFR 3 (HER3), an EGFR family member. Despite its significance, effective targeting of HER3 is still developing. This review aims to bridge this gap by deeply examining HER3’s pivotal contribution to EGFR TKI resistance and spotlighting emerging HER3-centered therapeutic avenues, including monoclonal antibodies (mAbs), TKIs, and antibody-drug conjugates (ADCs). Preliminary results indicate combining HER3-specific treatments with EGFR TKIs enhances antitumor effects, leading to an increased objective response rate (ORR) and prolonged overall survival (OS) in resistant cases. Embracing HER3-targeting therapies represents a transformative approach against EGFR TKI resistance and emphasizes the importance of further research to optimize patient stratification and understand resistance mechanisms.
Biomarkers and molecular endotypes of sarcoidosis: lessons from omics and non-omics studies
Authors: Ji Hong-Long , Xi Nan Mile S. , Mohan Chandra , Yan Xiting , Jain Krishan G. , Zang Qun Sophia , Gahtan Vivian , Zhao Runzhen
Published: January 2024

Sarcoidosis is a chronic granulomatous disorder characterized by unknown etiology, undetermined mechanisms, and non-specific therapies except TNF blockade. To improve our understanding of the pathogenicity and to predict the outcomes of the disease, the identification of new biomarkers and molecular endotypes is sorely needed. In this study, we systematically evaluate the biomarkers identified through Omics and non-Omics approaches in sarcoidosis. Most of the currently documented biomarkers for sarcoidosis are mainly identified through conventional “one-for-all” non-Omics targeted studies. Although the application of machine learning algorithms to identify biomarkers and endotypes from unbiased comprehensive Omics studies is still in its infancy, a series of biomarkers, overwhelmingly for diagnosis to differentiate sarcoidosis from healthy controls have been reported. In view of the fact that current biomarker profiles in sarcoidosis are scarce, fragmented and mostly not validated, there is an urgent need to identify novel sarcoidosis biomarkers and molecular endotypes using more advanced Omics approaches to facilitate disease diagnosis and prognosis, resolve disease heterogeneity, and facilitate personalized medicine.
Morphology of Hobagella saltata n. gen. and n. sp. (Syndiniophyceae, Miozoa) infecting the marine dinoflagellate Cucumeridinium coeruleum (Dinophyceae, Miozoa) and its potential onshore advection
Authors: Yoo Jiae , Kim Sunju , Coats D. Wayne
Published: January 2024

Over the past decade, molecular phylogenies have placed endoparasites of the genus Euduboscquella in a distinct subclade within clade 4 of the Marine Alveolate (MALV) Group I. Recently, however, rRNA gene sequences have become available for four novel Euduboscquella-like species that infect dinoflagellates, with phylogenies including these sequences indicating that the genus Euduboscquella is paraphyletic. Here, we provide a morphological characterization of the intracellular and extracellular life-cycle stages of a novel species that infects Cucumeridinium coeruleum, a warm water pelagic species sometimes found in coastal environments. We formally describe the novel parasite, Hobagella saltata n. gen, n. sp., and identify a constellation of morphological and developmental characters that distinguish it, as well as Euduboscquella melo and E. nucleocola, both parasites of dinoflagellates, from Euduboscquella species that infect ciliates. We recommend the reassignment of E. melo and E. nucleocola as Hobagella melo n. comb. and H. nucleocola n. comb., respectively. We also propose the family Hobagellidae for these three congeners. We anticipate that the character set developed for distinguishing species of Euduboscquella and Hobagella will be valuable for sorting other Euduboscquella-Hobagella-like taxa scattered across the Group I phylogeny and will provide insight into morphological evolutionary patterns within Group I. Lastly, we consider the potential influence of summer-fall typhoons on the occurrence of H. saltata and its host C. coeruleum in near-shore waters along the southeastern coast of Korea and propose a hypothesis regarding the northward transport and onshore advection of host and parasite populations. If future research supports the hypothesized mechanisms, it could help us better understand parasite distribution and potential changes in biogeography associated with ongoing global changes in surface seawater temperature.
Cumulative trophic curves elucidate tropical coral reef ecosystems
Authors: Link Jason S. , Pranovi Fabio , Zucchetta Matteo , Kindinger Tye L. , Heenan Adel , Tanaka Kisei R.
Published: January 2024

There are few generalizable patterns in ecology, with widespread observations and predictability. One possible generalizable pattern is the cumulative trophic theory, which consistently exhibits S-curves of cumulative biomass over trophic level (TL) for over 200 different marine ecosystems. But whether those cumulative biomass patterns persist in some of the more distinct marine ecosystems, coral reefs, is unclear. Coral reefs are unique among marine ecosystems, representing global biodiversity hotspots and providing crucial ecosystem services. They are subject to many pressures, including both global (e.g., climate and ocean changes, warming, acidification) and local (e.g., overexploitation/overfishing, increase in turbidity, bleaching, habitat destruction, invasive species) stressors. The analysis of emergent ecosystem features, such as cumulative biomass S-curves, could represent a useful and new analytical option that can also be implemented for coral reefs. The cumulative biomass approach was applied to 42 U.S. Pacific islands (Guam and the Commonwealth of Northern Mariana Islands, American Samoa, the Pacific Remote Islands Areas, and the Northwestern and Main Hawaiian Islands), using data collected from fish surveys. Results show that coral reef ecosystems do indeed follow the S-curve patterns expected from cumulative trophic theory, which is not trivial for tropical reef systems that tend to be less widely examined and strongly dominated by structuring organisms like corals. The curve parameters results are also consistent with both fish assemblage diversity indexes and the benthic substrate ratio, which suggests this measure could serve as a useful ecosystem indicator to measure the ecological status of reefs. Moreover, the curve shape was consistent with what one would expect for different levels of perturbation, with the areas more densely inhabited showing less pronounced S-curves, in contrast to those observed in low human population density islands. All this is reflected in the curve parameters, particularly inflection point of the TL and steepness, generally showing a negative response to both natural and anthropogenic disturbances. Cross-archipelago differences have also been detected with the Hawaiian Island chain tending to have lower inflection points for biomass and TL than other regions. Collectively our findings demonstrate the potential application of the cumulative biomass approach to evaluate coral reef ecosystems.
Clinical outcomes after implantation of a new monofocal intraocular lens with enhanced intermediate function in patients with preperimetric glaucoma
Authors: Chung Ho Seok , Jang Joon Hyuck , Lee Hun , Kim Jae Yong , Tchah Hungwon
Published: January 2024

Purpose

We evaluated the clinical outcomes after implantation of a new monofocal intraocular lens (IOL) with enhanced intermediate function in patients with preperimetric glaucoma and compared those with patients without retinal nerve fiber layer (RNFL) defects.

Methods

All patients were implanted bilaterally a new monofocal IOL with enhanced intermediate function. Patients with bilateral RNFL defects and no glaucomatous visual field defects were classified as the preperimetric glaucoma group. A total of 60 eyes of 30 patients with preperimetric glaucoma were compared with 60 eyes of 30 patients without RNFL defects. Uncorrected distance visual acuity (UDVA), uncorrected intermediate visual acuity (UIVA), uncorrected near visual acuity (UNVA), defocus curve, contrast sensitivity, and questionnaire were evaluated 1 month and 3 months after surgery.

Results

No difference in binocular UDVA, UIVA, and UNVA was evident between the two groups at 1 and 3 months postoperatively. Additionally, there were no significant differences between the two groups regarding the proportion of severe or very severe photic phenomena, such as glare and halos, or the overall satisfaction.

Conclusion

Bilateral implantation of a new monofocal IOL with enhanced intermediate function in patients with preperimetric glaucoma demonstrated commensurate clinical outcomes and could be considered a feasible alternative.
Evaluation of the corneal topography based on deep learning
Authors: Xu Shuai , Yang Xiaoyan , Zhang Shuxian , Zheng Xuan , Zheng Fang , Liu Yin , Zhang Hanyu , Li Lihua , Ye Qing
Published: January 2024

Purpose

The current study designed a unique type of corneal topography evaluation method based on deep learning and traditional image processing algorithms. The type of corneal topography of patients was evaluated through the segmentation of important medical zones and the calculation of relevant medical indicators of orthokeratology (OK) lenses.

Methods

The clinical data of 1,302 myopic subjects was collected retrospectively. A series of neural network-based U-Net was used to segment the pupil and the treatment zone in the corneal topography, and the decentration, effective defocusing contact range, and other indicators were calculated according to the image processing algorithm. The type of corneal topography was evaluated according to the evaluation criteria given by the optometrist. Finally, the method described in this article was used to evaluate the type of corneal topography and compare it with the type classified by the optometrist.

Results

When the important medical zones in the corneal topography were segmented, the precision and recall of the treatment zone reached 0.9587 and 0.9459, respectively, and the precision and recall of the pupil reached 0.9771 and 0.9712. Finally, the method described in this article was used to evaluate the type of corneal topography. When the reviewed findings based on deep learning and image processing algorithms were compared to the type of corneal topography marked by the professional optometrist, they demonstrated high accuracy with more than 98%.

Conclusion

The current study provided an effective and accurate deep learning algorithm to evaluate the type of corneal topography. The deep learning algorithm played an auxiliary role in the OK lens fitting, which could help optometrists select the parameters of OK lenses effectively.
Early introduction of simulation in the medical curriculum: the MedInTo perspective
Authors: Lembo David , Abate Daga Federico , Calì Corrado , Garbossa Diego , Manfredi Matteo , Odetto Lorenzo , Ostacoli Luca , Paccotti Piero , Raimondo Stefania , Reimondo Giuseppe , Sciascia Savino
Published: January 2024

Despite the increasing body of evidence supporting the use of simulation in medicine, a question remains: when should we introduce it into the medical school's curriculum? We present the experience and future perspectives of the MD program in Medicine and Surgery of University of Turin-MedInTo. Since its launch, MedInTo has been dedicated to integrating innovative teaching approaches at the early stages into the medical curriculum. Herewith, we describe a case-based approach for our activities, which includes the utilization of simulation for emergency medical care training for students and the integration of virtual and augmented reality technology. Dedicated surgical training activities using virtual-augmented reality and life-like simulator for students are also described.
Risk factors for symptomatic rotator cuff tears: a retrospective case–control study
Authors: Zhao Jinlong , Zeng Lingfeng , Liang Guihong , Luo Minghui , Yang Weiyi , Liu Jun , Pan Jianke
Published: January 2024

Background

The incidence and diagnostic rate of rotator cuff tears (RCTs) have increased significantly. The purpose of this study was to investigate and analyze the risk factors for symptomatic RCTs to provide a basis for their prevention and treatment.

Methods

We retrospectively analyzed the relevant clinical indicators of 193 patients with RCTs and 161 patients without RCTs hospitalized with shoulder pain as the main complaint from January 1, 2017, to August 31, 2021. Univariate analysis and multivariate logistic regression analysis were used to analyze the differences in potential risk factors between the two groups.

Results

Univariate analysis revealed that age (p < 0.001), body mass index (BMI) (p = 0.036), hypertension (p < 0.001), coronary heart disease (p = 0.028), history of shoulder trauma (p < 0.001), hyperlipidemia (p = 0.025), type III acromion (p = 0.012) and critical shoulder angle (CSA) (p < 0.001) increased the risk of RCTs. Multivariate logistic regression analysis revealed that age ≥ 60 years (OR = 2.61, 95% CI = 1.23 to 5.12), CSA ≥ 35° (OR = 4.24, 95% CI = 1.60 to 11.22), hypertension (OR = 2.34, 95% CI = 1.33 to 4.11) and history of shoulder trauma (OR = 5.20, 95% CI = 2.87 to 9.45) were independent risk factors for symptomatic RCTs.

Conclusion

The results of this study showed that age ≥ 60 years, CSA ≥35°, hypertension and history of shoulder trauma are independent risk factors for symptomatic RCTs and can provide directions for further development of prevention and treatment strategies. Future studies need to clarify the mechanism underlying the association between these risk factors and symptomatic RCTs.