bluuebunny/crossref_metadata_2025 huggingface dataset:
Temporal changes in glucose metabolism reflect polarization in resident and monocyte-derived macrophages after myocardial infarction
Authors: Mouton Alan J. , Aitken Nikaela M. , Moak Sydney P. , do Carmo Jussara M. , da Silva Alexandre A. , Omoto Ana C. M. , Li Xuan , Wang Zhen , Schrimpe-Rutledge Alexandra C. , Codreanu Simona G. , Sherrod Stacy D. , McLean John A. , Hall John E.
Published: May 2023

Introduction

Metabolic reprogramming from glycolysis to the mitochondrial tricarboxylic acid (TCA) cycle and oxidative phosphorylation may mediate macrophage polarization from the pro-inflammatory M1 to the anti-inflammatory M2 phenotype. We hypothesized that changes in cardiac macrophage glucose metabolism would reflect polarization status after myocardial infarction (MI), ranging from the early inflammatory phase to the later wound healing phase.

Methods

MI was induced by permanent ligation of the left coronary artery in adult male C57BL/6J mice for 1 (D1), 3 (D3), or 7 (D7) days. Infarct macrophages were subjected to metabolic flux analysis or gene expression analysis. Monocyte versus resident cardiac macrophage metabolism was assessed using mice lacking the Ccr2 gene (CCR2 KO).

Results

By flow cytometry and RT-PCR, D1 macrophages exhibited an M1 phenotype while D7 macrophages exhibited an M2 phenotype. Macrophage glycolysis (extracellular acidification rate) was increased at D1 and D3, returning to basal levels at D7. Glucose oxidation (oxygen consumption rate) was decreased at D3, returning to basal levels at D7. At D1, glycolytic genes were elevated (Gapdh, Ldha, Pkm2), while TCA cycle genes were elevated at D3 (Idh1 and Idh2) and D7 (Pdha1, Idh1/2, Sdha/b). Surprisingly, Slc2a1 and Hk1/2 were increased at D7, as well as pentose phosphate pathway (PPP) genes (G6pdx, G6pd2, Pgd, Rpia, Taldo1), indicating increased PPP activity. Macrophages from CCR2 KO mice showed decreased glycolysis and increased glucose oxidation at D3, and decreases in Ldha and Pkm2 expression. Administration of dichloroacetate, a pyruvate dehydrogenase kinase inhibitor, robustly decreased pyruvate dehydrogenase phosphorylation in the non-infarcted remote zone, but did not affect macrophage phenotype or metabolism in the infarct zone.

Discussion

Our results indicate that changes in glucose metabolism and the PPP underlie macrophage polarization following MI, and that metabolic reprogramming is a key feature of monocyte-derived but not resident macrophages.
The therapeutic concordance approach reduces adverse drug reactions in patients with resistant hypertension
Authors: Trimarco Valentina , Manzi Maria Virginia , Izzo Raffaele , Mone Pasquale , Lembo Maria , Pacella Daniela , Esposito Giovanni , Falco Angela , Morisco Carmine , Gallo Paola , Santulli Gaetano , Trimarco Bruno
Published: May 2023

Background

Adverse drug reactions (ADRs) remain among the leading causes of therapy-resistant hypertension (TRH) and uncontrolled blood pressure (BP). We have recently reported beneficial results in BP control in patients with TRH adopting an innovative approach, defined as therapeutic concordance, in which trained physicians and pharmacists reach a concordance with patients to make them more involved in the therapeutic decision-making process.

Methods

The main scope of this study was to investigate whether the therapeutic concordance approach could lead to a reduction in ADR occurrence in TRH patients. The study was performed in a large population of hypertensive subjects of the Campania Salute Network in Italy (ClinicalTrials.gov Identifier: NCT02211365).

Results

We enrolled 4,943 patients who were firstly followed-up for 77.64 ± 34.44 months, allowing us to identify 564 subjects with TRH. Then, 282 of these patients agreed to participate in an investigation to test the impact of the therapeutic concordance approach on ADRs. At the end of this investigation, which had a follow-up of 91.91 ± 54.7 months, 213 patients (75.5%) remained uncontrolled while 69 patients (24.5%, p < 0.0001) reached an optimal BP control. Strikingly, during the first follow-up, patients had complained of a total of 194 ADRs, with an occurrence rate of 68.1% and the therapeutic concordance approach significantly reduced ADRs to 72 (25.5%).

Conclusion

Our findings indicate that the therapeutic concordance approach significantly reduces ADRs in TRH patients.
Case report: Use of three-dimensional technology in criss-cross heart with double outlet right ventricle
Authors: Alifu Ailixiati , Wang Haifan , Su Yuntian , Chen Renwei
Published: May 2023

Background

In this case report, we utilized a three-dimensional printing model to replicate the complex anatomy of a criss-cross heart with double outlet right ventricle—an extremely rare congenital cardiac abnormality. This approach facilitated our understanding of the patient's unique condition and enabled us to plan the surgical procedure with greater precision.

Case presentation

Our department received a 13-year-old female patient who presented with a pronounced heart murmur and a decrease in exercise capacity. Subsequent two-dimensional imaging revealed the presence of a criss-cross heart with double outlet right ventricle—an intricate and uncommon cardiac malformation that poses challenges for accurate visualization through conventional two-dimensional modalities. To address this challenge, we constructed and printed a three-dimensional model using computed tomography data, which enabled us to visualize and understand the complex intracardiac structures and plan surgical interventions with greater precision. Using this approach, we successfully performed a right ventricular double outlet repair, and the patient made a full recovery following the procedure.

Conclusion

The criss-cross heart with double outlet right ventricle constitutes a complex and uncommon cardiac anomaly that poses considerable challenges in terms of diagnosis and surgical intervention. Employing three-dimensional modeling and printing represents a promising approach, given its potential to enhance the precision and comprehensiveness of the anatomical evaluation of the heart. As a result, this method holds significant promise in facilitating accurate diagnosis, meticulous surgical planning, and ultimately improving clinical outcomes for patients affected by this condition.
Assessment of the Magdalena River delta socio-ecological system through the Circles of Coastal Sustainability framework
Authors: Gallo-Vélez David , Restrepo Juan Camilo , Newton Alice
Published: May 2023

River-mouth systems and deltas are hotspots where many of the coastal syndromes can be found. Moreover, these systems provide essential ecosystem services (e.g., recreation, food provisioning, protection against natural hazards). The present study focuses on the socio-ecological system at the delta of the Magdalena River in the central Caribbean Region in Colombia. This research seeks to assess the multidimensional sustainability of the Magdalena river-mouth system (MRm-SES) to improve the knowledge basis for its integrated management. To do so, an assessment tool named “Circles of Coastal Sustainability” (CCS) was used to evaluate the system splitting it into four domains (environmental, social, economic and governance) that were divided into 5 categories each. These domains were evaluated through a total of 52 indicators distributed like this: 16 for the Environmental domain, 16 for the Economic domain, 12 for the Social and Cultural domain and, 8 for the Governance domain. The results show that the overall sustainability of the MRm-SES is classified as “Satisfactory.” None of the domains is in “Excellent” or “Bad” conditions. However, the evaluation of the categories shows that four (4) of them have “Poor” conditions (i.e., Social Benefits, Demographics, Economic Security, and Resources Management). Hence, it is recommended to put those categories at the centre of the discussion to define management strategies (e.g., Preserving and restoring habitats; tackling sources of pollution and excessive sediment; local reduction of net Greenhouse Gas and adaptation to climate change; participation of local communities in the management design and implementation), without disregarding the interrelation with the other categories and dimensions. Finally, it is argued that despite all the improvement opportunities, the CCS is a valuable tool to evaluate and communicate with different stakeholders (academic community, managers and decision-makers, local communities, etc.), to improve the sustainability of coastal systems in Colombia and the world.
Weak degassing from remote Alaska volcanoes characterized with a new airborne imaging DOAS instrument and a suite of in situ sensors
Authors: Kern Christoph , Kelly Peter J.
Published: May 2023

Gas emissions from volcanoes occur when volatile species exsolve from magmatic and hydrothermal systems and make their way to the surface. Measurements of emitted gases therefore provide insights into volcanic processes. On 16 July 2021, we made airborne measurements of weak gas plumes emitted from four remote Alaska volcanoes: Iliamna Volcano, Mount Douglas, Mount Martin, and Mount Mageik. Integrated into a small fixed-wing aircraft, a new Imaging Differential Optical Absorption Spectroscopy (DOAS) instrument was used to map the spatial extent of SO2 plumes as they drifted downwind. Contrary to conventional Mobile DOAS instruments, which provide only a single viewing direction, the Imaging DOAS simultaneously measures SO2 column density along 48 individual viewing directions oriented in a swath above or below the aircraft. Each of the individual measurements have a comparable precision and sensitivity to those obtained by conventional instruments. Together, they provide high resolution 2D imagery of the volcanic plumes and allow calculation of limited emission rate time series information. Although zenith-facing DOAS measurements achieve greater accuracy and are performed here, the application of the Imaging DOAS in a nadir-facing setup is also discussed and compared to satellite observations made in similar geometries. Also onboard the aircraft, a suite of electrochemical and optical sensors measured the relative abundances of the six major volcanic volatile species H2O, CO2, SO2, H2S, HCl, and HF as the aircraft passed through the plumes. Mean SO2 emission rates of 90 ± 10, 20 ± 3, and 13 ± 3 t/d were measured at Iliamna Volcano, Mount Douglas, and Mount Martin, respectively. SO2 emissions were below the DOAS detection limit at Mount Mageik but CO2 and H2S could be measured with the in situ sensors. The information gleaned from these measurements was used to assess and compare activity at these volcanoes, all of which were found to be in a state of background degassing but whose emissions pointed to different source conditions ranging from mixed magmatic-hydrothermal to purely hydrothermal in character. Additional measurements at Mount Spurr, Redoubt Volcano, and Augustine Volcano failed to detect the very weak gas concentrations downwind of these persistently degassing vents.
Promoting future teachers’ evidence-informed reasoning scripts: Effects of different forms of instruction after problem-solving
Authors: Krause-Wichmann Theresa , Greisel Martin , Wekerle Christina , Kollar Ingo , Stark Robin
Published: May 2023

Pre-service teachers face difficulties when dealing with problem situations in the classroom if their evidence-informed reasoning script (EIRS) is not adequately developed. An EIRS might be promoted by demonstrating how to implement evidence-informed reasoning after a problem-solving activity on an authentic case. However, it is unclear what form of instruction is appropriate to promote pre-service teachers in the development of an EIRS. The present 2×3-factorial experimental intervention study investigated how different forms of instruction on functional procedures (example-free vs. example-based) and on dysfunctional procedures (without vs. example-free vs. example-based) affect the development of an EIRS. N = 384 pre-service teachers worked on a written case vignette of a problem situation in a problem-solving phase, in which the crucial steps of the EIRS were prompted externally. In the subsequent instruction phase, the participants compared their own solution with an example-free or example-based instruction on functional procedures, which was either supplemented by an example-free or example-based instruction on typical dysfunctional procedures or not at all. The participants’ learning success (declarative EIRS; near and far transfer problem-solving performance) and error awareness were assessed. The results revealed that the example-based instruction on functional procedures led to a higher learning success than the example-free instruction. Both forms of instruction on dysfunctional procedures improved learning success compared to learning without one. During learning, error awareness was higher for learners who worked with an example-free instruction on dysfunctional procedures. In order to promote the development of an EIRS in pre-service teachers, it is promising to provide instruction after problem-solving that presents a functional example of evidence-informed reasoning for the given problem and that also points out typical dysfunctional approaches to solving the problem. The results highlight the importance of selecting appropriate scaffolds in case-based learning approaches that aim to develop cognitive schemata. The mechanisms that explain when and why instructions on dysfunctional procedures work need to be further explored.
Effect of fruit on glucose control in diabetes mellitus: a meta-analysis of nineteen randomized controlled trials
Authors: Ren Yu , Sun Shuang , Su Yongwei , Ying Chenfei , Luo Hua
Published: May 2023

Objective

Diabetes mellitus is a worldwide health problem, and it remains unclarified whether fruit is beneficial in glycemic control. This study aimed to analyze evidence from randomized controlled trials evaluating the effect of fruit consumption on glucose control.

Methods

We searched the PubMed, EMBASE, Ovid, Web of Science, and Cochrane Central Register of Controlled Trials databases from the respective database inception dates to December 30, 2022, to identify randomized controlled trials that evaluated the effects of fruit consumption on glucose control. Two researchers independently screened the studies in accordance with the inclusion and exclusion criteria, and performed the literature quality evaluation and data extraction. RevMan 5.4 software was used to perform the data analysis.

Results

Nineteen randomized controlled trials with 888 participants were included. Fruit consumption significantly decreased the fasting blood glucose concentration (MD -8.38, 95% CI -12.34 to -4.43), but it showed no significant difference in the glycosylated hemoglobin (MD -0.17, 95% CI -0.51 to 0.17). Subgroup analyses further suggested that the consumption of both fresh and dried fruit decreased the fasting blood glucose concentration.

Conclusions

Increasing the fruit intake reduced fasting blood glucose concentration. Therefore, we recommend that patients with diabetes eat more fruits while ensuring that their total energy intake remains unchanged.
A capacity optimization and scheduling scheme of a multi-energy complementary power station considering energy trading
Authors: Zou Shaokun , Zhang Ning , Wei Baoze
Published: May 2023

Digital technology is rapidly advancing, and the resulting digitization of energy is becoming an inevitable trend. Integrating digital technology with energy planning can enable efficient utilization of renewable energy (RE); the fluctuation of RE generation, such as wind and photovoltaic (PV), can be reduced, and the reliability of the power grid can be ensured. A better solution for RE utilization and planning based on digital technology is proposed in this paper. First, an operation mechanism of a multi-energy complementary power station is proposed based on the complementary characteristics of multiple energy sources in the power generation process. The current status and related issues of multi-energy complementary power stations are studied in this paper. Second, a two-layer model of optimization that integrates the complementary features of multiple energy sources and system planning requirements is developed in this paper based on the aforementioned power station operation mechanism. The two layers of the model are nested with each other to realize the operation of the power station. The upper model includes the RE utilization rate and the benefits of the energy storage (ES) system. The lower model includes the operating cost of the power station. The solution model includes the highest utilization rate of RE and the lowest operation cost. Finally, the simulation operation is performed based on the data on a provincial power grid. The model and operation strategy of the multi-energy complementary power station based on digital technology proposed by this paper are verified.
Does phosphogypsum addition affect phosphate rock dissolution in acid soils?
Authors: Bouray Moussa , Moir Jim , El Mejahed Khalil , Choukr-Allah Redouane , El Gharous Mohamed
Published: May 2023

The direct application of phosphate rock (PR) has been found suitable for acidic soils. Still, efforts are needed to improve its reactivity to match grassland P demand. This research aimed to investigate changes in the dissolution of two Moroccan sedimentary PRs (Ben Guerir and Khouribga) in response to four rates of phosphogypsum (PG)—a by-product of the phosphate fertilizer industry. We conducted a 60-day incubation study using two acid soils from New Zealand. The soils were treated with PRs at 100 mgP kg−1 of soil either alone or combined with PG, which was applied at 0, 1, 3 and 9 t ha−1 (approximately the equivalent of 0, 0.9, 2.7, and 8.1 g of PG kg−1 of soil, respectively). The dissolution rates were determined from the differences in residual calcium (Ca) extracted with 1 M HCl. Soil pH, Olsen P, exchangeable aluminium (Al) and Ca and Ca saturation were analyzed at the end of the experiment. Phosphate rocks and PG’s physicochemical properties were characterized. Phosphogypsum addition increased Olsen P by 34% and 59% at 9 t ha−1 compared to 0 t ha−1 in Molesworth and Lindis Peaks soils, respectively. However, PG did not affect the dissolution of PRs in the different of soil types. Khouribga PR was more reactive than Ben Guerir PR, especially in the Molesworth soil where soil pH and base saturation were lower and P retention was higher compared to Lindis Peaks soil. Particle size distribution was the key factor that contributed to the observed greater reactivity of the Khouribga PR. Both PRs showed dissolution rates >50%, suggesting their suitability for direct application on acid soils. Being an important source of sulphur and some P, PG if combined with PR, can promote and complement PR’s direct use as fertilizer on acid soils. Moreover, the development of new fertilizer products by combining these two materials should be encouraged.
Racial/ethnic and socioeconomic disparities in COVID-19 infections among working-age women with precancerous cervical lesion in Louisiana: analysis of more than two years of COVID-19 data
Authors: Hsieh Mei-Chin , Lefante Christina , Straif-Bourgeois Susanne , Yi Yong , Gomez Natalie , Shrestha Pratibha , Chen Vivien W. , Wu Xiao-Cheng
Published: May 2023

Background

Precancerous cervical lesion (PCL) is common in working-age and minority women. In Louisiana, 98% of PCL cases were diagnosed at age 18–65 with over 90% of them being human papillomavirus (HPV)-related. PCL women represent those who may be immunocompromised from the precancerous condition and thus more vulnerable to SARS-CoV-2. Most studies evaluating racial disparities for COVID-19 infection have only used data prior to vaccine availability. This study assessed disparities by race/ethnicity and socioeconomic status (SES) in COVID-19 infections among working-age PCL women for pre- and post-COVID-19 vaccine availability.

Methods

Louisiana women aged 18–65 with PCL diagnosed in 2009–2021 were linked with the Louisiana statewide COVID-19 database to identify those with positive COVID-19 test. Race/ethnicity was categorized as non-Hispanic white (NHW), non-Hispanic black (NHB), Hispanic, and others. The census tract SES quintiles were created based on American Community Survey estimates. Logistic regression was employed to assess the racial/ethnic and SES differences in COVID-19 infections.

Results

Of 14,669 eligible PCL women, 30% were tested COVID-19 positive. NHB had the highest percentage of COVID-19 infection (34.6%), followed by NHW (27.7%). The infection percentage was inversely proportional to SES, with 32.9% for women having the lowest SES and 26.8% for those with the highest SES. NHB women and those with lower SES had higher COVID-19 infection than their counterparts with an aOR of 1.37 (95% CI 1.25–1.49) and 1.21 (95% CI 1.07–1.37), respectively. In the pre-vaccine period, NHB and Hispanic women had higher odds of infection than NHW women. However, after the vaccine was implemented, the significant racial/ethnic and SES differences in COVID-19 infections still existed in PCL women residing in non-Greater New Orleans area.

Conclusions

There are substantial variations in racial/ethnic and SES disparities in COVID-19 infections among working-age women with PCL, even after vaccine implementation. It is imperative to provide public health interventions and resources to reduce this unequal burden for this vulnerable population.
Exploring spatio-temporal patterns of palynological changes in Asia during the Holocene
Authors: Bhatta Kuber P. , Mottl Ondřej , Felde Vivian A. , Flantua Suzette G. A. , Birks Hilary H. , Cao Xianyong , Chen Fahu , Grytnes John-Arvid , Seddon Alistair W. R. , Birks Harry John B.
Published: May 2023

Historical legacies influence present-day ecosystem composition and dynamics. It is therefore important to understand the long-term dynamics of ecosystems and their properties. Analysis of ecosystem properties during the Holocene using fossil pollen assemblages provides valuable insights into past ecosystem dynamics by summarising so-called pollen-assemblage properties (PAPs). Using 205 fossil pollen data-sets (records), we quantify eight PAPs [pollen-taxonomic richness, diversity, evenness, pollen-compositional turnover, pollen-compositional change, and rate of pollen-compositional change (RoC)] for the Asian continent at different spatial scales (in individual records, within and across climate-zones, and within the continent) and time (temporal patterns over the past 12,000 years). Regression tree (RT) partitioning of the PAP-estimates using sample-age as a sole predictor revealed the “change-point(s)” (time or sample-age of major change in a PAP). We estimated the density of RT and multivariate regression tree (MRT) change-points in 1,000-year time bins during the Holocene. Pollen-compositional turnover (range of sample scores along the first DCCA axis) and change (number of MRT partitions) in each record reveal gradual spatial variation across latitude and a decline with longitude eastward. Temporally, compositional turnover declines linearly throughout the Holocene at all spatial scales. Other PAPs are heterogeneous across and within spatial scales, being more detectable at coarser scales. RT and MRT change-point density is broadly consistent in climate-zones and the continent, increasing from the early- to mid-Holocene, and mostly decrease from the mid-Holocene to the present for all PAPs. The heterogenous patterns in PAPs across the scales of study most likely reflect responses to variations in regional environmental conditions, anthropogenic land-use, and their interactions over space and time. Patterns at the climate-zone and continental scales indicate a gradual but congruent decline in major PAPs such as compositional turnover, rate of compositional change, and major temporal compositional changes (MRT) during the Holocene, especially during recent millennia, suggesting that vegetation in Asia has become progressively more homogenous. Data properties (e.g., spatial distribution of the records, distribution of samples within the records, and data-standardisation and analytical approaches) may also have partly influenced the results. It is critically important to evaluate the data properties and the approaches to data standardisation and summarisation.
Freshwater insect communities in urban environments around the globe: a review of the state of the field
Authors: Ferzoco Ilia Maria C. , Murray-Stoker Kelly M. , Hasan Lina Salam , Javier Celina M. , Modi Vatsaa , Singh Rupinder , Tjan Grace , Toth Olivia , McCauley Shannon J.
Published: May 2023

Urbanization is a key stressor of freshwater habitats, possibly contributing to global insect declines. However, scientific understanding of urbanization's effects on aquatic insect communities has largely been based on studies of temperate streams. We reviewed global urban freshwater macroinvertebrate community studies, classifying habitat type, location, urbanization metrics, biodiversity metrics, and focal taxa, drawing from 114 studies in 32 different countries. Our goals were to: (1) investigate the extent of research on urbanization across a variety of freshwater habitats, (2) examine the representation in empirical literature across the globe by comparing cities in different geographic regions, and (3) highlight how study approaches including taxonomic resolution and the inclusion of trait data impact interpretation of these patterns. Most studies were conducted in North America and Europe, but there is growing representation from other continents. Additionally, lentic environments were underrepresented in the literature on community responses to urbanization compared to lotic studies. Therefore, we suggest that lentic habitats should be investigated more thoroughly. We suggest that future empirical studies should incorporate traits of the taxa investigated to better predict how communities respond to urban stressors. The lack of consistent results from the reviewed studies showed that there is no single, predictable effect of urbanization, indicating that future meta-analyses and review papers should consider the potential context-dependency of freshwater insect responses to anthropogenic pressures. Our goal in highlighting understudied environmental and regional contexts is to move toward holistically addressing the ongoing challenges of urban freshwater insect conservation and freshwater ecology research.
Neurotransmitters: promising immune modulators in the tumor microenvironment
Authors: Xiao Luxi , Li Xunjun , Fang Chuanfa , Yu Jiang , Chen Tao
Published: May 2023

The tumor microenvironment (TME) is modified by its cellular or acellular components throughout the whole period of tumor development. The dynamic modulation can reprogram tumor initiation, growth, invasion, metastasis, and response to therapies. Hence, the focus of cancer research and intervention has gradually shifted to TME components and their interactions. Accumulated evidence indicates neural and immune factors play a distinct role in modulating TME synergistically. Among the complicated interactions, neurotransmitters, the traditional neural regulators, mediate some crucial regulatory functions. Nevertheless, knowledge of the exact mechanisms is still scarce. Meanwhile, therapies targeting the TME remain unsatisfactory. It holds a great prospect to reveal the molecular mechanism by which the interplay between the nervous and immune systems regulate cancer progression for laying a vivid landscape of tumor development and improving clinical treatment.
Determinants of tumor immune evasion: the role of T cell exposed motif frequency and mutant amino acid exposure
Authors: Homan E. Jane , Bremel Robert D.
Published: May 2023

Few neoepitopes detected in tumor biopsies are immunogenic. Tumor-specific T cell responses require both the presentation of an epitope that differs from wildtype and the presence of T cells with neoepitope-cognate receptors. We show that mutations detected in tumor biopsies result in an increased frequency of rare amino acid combinations compared to the human proteome and gastrointestinal microorganisms. Mutations in a large data set of oncogene and tumor suppressor gene products were compared to wildtype, and to the count of corresponding amino acid motifs in the human proteome and gastrointestinal microbiome. Mutant amino acids in T cell exposed positions of potential neoepitopes consistently generated amino acid motifs that are less common in both proteome reference datasets. Approximately 10% of the mutant amino acid motifs are absent from the human proteome. Motif frequency does not change when mutants were positioned in the MHC anchor positions hidden from T cell receptors. Analysis of neoepitopes in GBM and LUSC cases showed less common T cell exposed motifs, and HLA binding preferentially placing mutant amino acids in an anchor position for both MHC I and MHC II. Cross-presentation of mutant exposed neoepitopes by MHC I and MHC II was particularly uncommon. Review of a tumor mutation dataset known to generate T cell responses showed immunogenic epitopes were those with mutant amino acids exposed to the T cell receptor and with exposed pentamer motifs present in the human and microbiome reference databases. The study illustrates a previously unrecognized mechanism of tumor immune evasion, as rare T cell exposed motifs produced by mutation are less likely to have cognate T cells in the T cell repertoire. The complex interactions of HLA genotype, binding positions, and mutation specific changes in T cell exposed motif underscore the necessity of evaluating potential neoepitopes in each individual patient.
Heme oxygenase-1 determines the cell fate of ferroptotic death of alveolar macrophages in COPD
Authors: Li Yi , Yang Ying , Guo Tingting , Weng Chengxin , Yang Yongfeng , Wang Zhoufeng , Zhang Li , Li Weimin
Published: May 2023

Background

Despite an increasing understanding of chronic obstructive pulmonary disease (COPD) pathogenesis, the mechanisms of diverse cell populations in the human lung remain unknown. Using single-cell RNA sequencing (scRNA-Seq), we can reveal changes within individual cell populations in COPD that are important for disease pathogenesis and characteristics.

Methods

We performed scRNA-Seq on lung tissue obtained from donors with non-COPD and mild-to-moderate COPD to identify disease-related genes within different cell types. We testified the findings using qRT−PCR, immunohistochemistry, immunofluorescence and Western blotting from 25 additional subjects and RAW 264.7 macrophages. Targeting ferroptosis with the ferroptosis inhibitor ferrostatin-1, iron chelator deferoxamine or HO-1 inhibitor zinc protoporphyrin was administered in the experimental cigarette smoke COPD mouse model.

Results

We identified two populations of alveolar macrophages (AMs) in the human lung that were dysregulated in COPD patients. We discovered that M2-like AMs modulate susceptibility to ferroptosis by disrupting lipid and iron homeostasis both in vivo and in vitro. The discrepancy in sensitivity to ferroptosis can be determined and regulated by HO-1. In contrast, M1-like AMs showed the ability to attenuate oxidative stress and exert resistance to ferroptosis. In addition, the expression of genes within M2-like AMs is also involved in defects in phagocytosis and lysosome distortion. This ferroptotic phenotype was ameliorated by antiferroptotic compounds, iron chelators and HO-1 inhibitors. During COPD, the accumulation of lipid peroxidation drives ferroptosis-sensitive M2-like AMs, while M1-like AMs show characteristics of ferroptosis resistance. Ferroptotic M2 AMs lose their anti-inflammatory and repair functions but provoke inflammatory responses, resulting in consistent inflammation and tissue damage in the presence of M1 AMs in COPD.

Conclusion

Appropriate interventions in ferroptosis can reduce the occurrence of infections and acute onset, and delay the COPD process.
The molecular mechanism of Gorham syndrome: an update
Authors: Xiang Juqin , Zhong Weiyang
Published: May 2023

Gorham syndrome, also known as “vanishing osteopathy” and “invasive hemangiomatosis,” is a rare clinical syndrome whose etiology is unknown and can invade the whole-body skeleton. At present, more than 300 cases have been reported at home and abroad, usually manifesting as spontaneous chronic osteolysis with no periosteal reaction at the lysis site and occult onset, often with fractures, scoliosis, chylothorax, etc. When waiting for medical treatment, the condition is serious, and the prognosis is poor. At present, there is no effective treatment. The main pathological manifestations of Gorham syndrome are the non-neoplastic abnormal proliferation of lymphatic vessels or blood vessels and osteolysis caused by osteoclast proliferation or increased activity. At present, there is no unified conclusion regarding Gorham syndrome’s pathogenesis. This paper starts with the two most studied osteolysis methods at present, osteoclast osteolysis and osteolysis caused by vascular and lymphatic proliferation and summarizes the corresponding most possible molecular mechanisms in recent years to provide more ideas for Gorham syndrome treatment.
Epigenetically altered macrophages promote development of diabetes-associated atherosclerosis
Authors: Huang Dong , Gao Wei , Zhong Xin , Wu Hongxian , Zhou You , Ma Yuanji , Qian Juying , Ge Junbo
Published: May 2023

Background

Atherosclerosis (AS) risk is elevated in diabetic patients, but the underlying mechanism such as involvement of epigenetic control of foam macrophages remains unclear. We have previously shown the importance of immune regulation on endothelial cells to AS development in diabetes. In this study, we examined the hypothesis that diabetes may promote AS through modification of the epigenetic status of macrophages.

Methods

We employed the Laser Capture Microdissection (LCM) method to evaluate the expression levels of key epigenetic regulators in both endothelial cells and macrophages at the AS lesions of patients. We then assessed the correlation between the significantly altered epigenetic regulator and serum levels of low-density Lipoprotein (LDL), triglycerides (TRIG) and high-density Lipoprotein (HDL) in patients. In vitro, the effects of high glucose on glucose utilization, lactate production, succinate levels, oxygen consumption and polarization in either undifferentiated or differentiated bone marrow-derived macrophages (BMDMs) were analyzed. The effects of depleting this significantly altered epigenetic regulator in macrophages on AS development were assessed in AS-prone diabetic mice.

Results

Histone deacetylase 3 (HDAC3) was identified as the most significantly altered epigenetic regulator in macrophages from the AS lesions in human diabetic patients. The levels of HDAC3 positively correlated with high serum LDL and TRIG, as well as low serum HDL. High glucose significantly increased glucose utilization, lactate production, succinate levels and oxygen consumption in cultured macrophages, and induced proinflammatory M1-like polarization. Macrophage depletion of HDAC3 significantly attenuated AS severity in AS-prone diabetic mice.

Conclusion

Epigenetically altered macrophages promote development of diabetes-associated AS, which could be prevented through HDAC3 depletion.
Field survey and analysis of water flux and salinity gradients considering the effects of sea ice coverage and rubber dam: a case study of the Liao River Estuary, China
Authors: Hu Zhanming , Guo Kaiyuan , Yang Yongjun , Zhang Mingliang
Published: May 2023

Predicting net river fluxes is important to promote good water quality, maritime transport, and water exchange in estuaries. However, few studies have observed and evaluated net water fluxes to estuaries under complex conditions. This study used advanced survey techniques to obtain high-frequency monitoring data of cross-sectional current velocity, water level, and salinity in the Liao River Estuary (LRE) from 2017 to 2020. The net water flux into the sea was computed based on field data and the impacts of the rubber dam and sea ice cover on water flux and salinity processes were analyzed in the study region. In the Liao River Station (LRS), the fluctuations of water level and discharge were not obvious in winter due to the sea ice cover. There were significant seasonal and inter-annual changes in water fluxes due to variability in river discharge and tidal oscillations. The results also showed that the net water flux into the sea from the LRS was positive in wet season, and greater during ebb tides than flood tides. The net water fluxes in the normal and dry seasons were mostly negative due to the influence of tides, indicating that the annual runoff from the Liao River fluctuated greatly throughout the year. The water flux in the LRS was more suitable for representing water flux into the sea than the Liujianfang Hydrometric Station (LHS) in the LRE. The impacts of the rubber dam and Panshan Sluice on water fluxes to the sea were both significant. Lower salinity in the study area coincided mostly with height water fluxes to the sea and periods when the rubber dam was raised. This study results provide us new insights to measure the water flux into sea under the condition of ice cover in the tidal reach of estuary and the method can be used for water flux observation for other estuaries.
An integrated catch-at-age model for analyzing the variability in biomass of Pacific sardine (Sardinops sagax) from the Gulf of California, Mexico
Authors: Nevárez-Martínez Manuel O. , Morales-Bojórquez Enrique , Martínez-Zavala María de los Ángeles , Villalobos Héctor , Luquin-Covarrubias Marlene A. , González-Máynez Violeta E. , López-Martínez Juana , Santos-Molina J. Pablo , Ornelas-Vargas Arelly , Delgado-Vences Francisco
Published: May 2023

Knowledge of the population dynamics and changes in the abundance of Pacific sardine fishery is relevant for fishery management. In this study, an integrated catch-at-age model (ASAP) was performed on 47 fishing seasons (1971−2018) ofSardinops sagaxin the Gulf of California, including five indices of relative abundance (survey catch rate, acoustic surveys, egg and larvae, spawning probability, and bird diet index). The ASAP model showed the importance of age group 0 (recruits); this is the most important age group in the Pacific sardine fishery, and its abundance has consequences for the variability of the total abundance of the species. In this study, the spawning and acoustic indices denoted the changes in abundance of Pacific sardine population better than the survey catch rate and bird diet ratio. Historically, the total biomass is estimated to have varied from 461 thousand to 4.82 million t. In the 1970s and 1980s, a peak biomass close to three million tons was reached, and in the second peak from the mid-1990s to the late 2000s, the total biomass varied between 3.26 and 4.82 million t. When the spawning biomass was at least 750 x 103t, the recruitment (age group 0) showed high values, promoting high catches in the subsequent years. The annual fishing mortality estimates did not show a rise related to the periods of high harvestable biomass; therefore, the catch records were low in comparison to the harvestable biomass estimated from ASAP, and the annual fishing mortalities were less than 0.22 during periods of high abundance. The changes in biomass and the variability observed in the Pacific sardine fishery were validated for the model diagnostics; the retrospective patterns did not identify poor fits to data, therefore the robustness of the model can be used for management purposes. According to the Kobe phase plot, the Pacific sardine fishery in the Gulf of California has been fully exploited with an apparent stable level of harvest.
Optical observations and spatio-temporal projections of gelatinous zooplankton in the Fram Strait, a gateway to a changing Arctic Ocean
Authors: Pantiukhin Dmitrii , Verhaegen Gerlien , Kraan Casper , Jerosch Kerstin , Neitzel Philipp , Hoving Henk-Jan T. , Havermans Charlotte
Published: May 2023

Global warming causes profound environmental shifts in the Arctic Ocean, altering the composition and structure of communities. In the Fram Strait, a transitional zone between the North-Atlantic and Arctic Ocean, climate change effects are particularly pronounced and accelerated due to an increased inflow of warm Atlantic water. Gelatinous zooplankton are known as key predators, consuming a great variety of prey and playing an important role in marine ecosystems. Insufficient knowledge of how gelatinous zooplankton are affected by environmental change has resulted in a notable gap in the understanding of the future state of Arctic ecosystems. We analyzed the diversity and abundance of gelatinous zooplankton down to 2600 m depth and established the first regional baseline dataset using optical observations obtained by the towed underwater camera system PELAGIOS (Pelagic In situ Observation System). Our data estimate the abundance of 20 taxa of gelatinous zooplankton. The most abundant taxa belong to the family of Rhopalonematidae, mainly consisting of Aglantha digitale and Sminthea arctica, and the suborder Physonectae. Using the observational data, we employed a joint species distribution modelling approach to better understand their distributional patterns. Variance partitioning over the explanatory variables showed that depth and temperature explained a substantial amount of variation for most of the taxa, suggesting that these parameters drive diversity and distribution. Spatial distribution modelling revealed that the highest abundance and diversity of jellyfish are expected in the marginal sea-ice zones. By coupling the model with climate scenarios of environmental changes, we were able to project potential changes in the spatial distribution and composition of gelatinous communities from 2020 to 2050 (during the summer season). The near-future projections confirmed that with further temperature increases, gelatinous zooplankton communities in the Fram Strait would become less diverse but more abundant. Among taxa of the Rhopalonematidae family, the abundance of Aglantha digitale in the entire water column would increase by 2%, while a loss of up to 60% is to be expected for Sminthea arctica by 2050. The combination of in situ observations and species distribution modelling shows promise as a tool for predicting gelatinous zooplankton community shifts in a changing ocean.
Development and validation of method for analysis of favipiravir and remdesivir in volumetric absorptive microsampling with ultra high-performance liquid chromatography–tandem mass spectrophotometry
Authors: Harahap Yahdiana , Noer Roesytas Fitria , Simorangkir Timbul Partogi H.
Published: May 2023

Favipiravir and remdesivir are drugs to treat COVID-19. This study aims to find an optimum and validated method for simultaneous analysis of favipiravir and remdesivir in Volumetric Absorptive Microsampling (VAMS) by Ultra High-Performance Liquid Chromatography–Tandem Mass Spectrophotometry. The use of VAMS can be an advantage because the volume of blood is small and the sample preparation process is simple. Sample preparation was done by precipitation of protein using 500 μL of methanol. Analysis was carried out by ultra high-performance liquid chromatography–tandem mass spectrophotometry with ESI+ and MRM with m/z 157.9 > 112.92 for favipiravir, 603.09 > 200.005 for remdesivir, and at m/z 225.968 > 151.991 for acyclovir as the internal standard. The separation was carried out using an Acquity UPLC BEH C18 column (100 × 2.1 mm; 1.7 m), 0.2% formic acid—acetonitrile (50:50), flow rate was 0.15 mL/min, and column temperature was 50°C. The analytical method has been validated with the requirements issued by the Food and Drug Administration (2018) and European Medicine Agency (2011). The calibration range of favipiravir is 0.5–160 μg/mL and 0.002–8 μg/mL for remdesivir.
Iguratimod as an alternative therapy for systemic sclerosis and prevention of the occurrence of ischemic digital ulcer
Authors: Yan Qingran , Liu Bei , Wang Jieying , Yin Hanlin , Li Qianqian , Lu Liangjing
Published: May 2023

Objectives

This study aimed to assess the effectiveness of iguratimod (IGU) as an alternative treatment for systemic sclerosis (SSc), especially in the prevention of ischemic digital ulcers (DUs).

Methods

We constructed two cohorts from the Renji SSc registry. In the first cohort, SSc patients receiving IGU were observed prospectively with effectiveness and safety. In the second cohort, we picked up all the DU patients with at least a 3-month follow-up to investigate the prevention of IGU on ischemic DU.

Results

From 2017 to 2021, 182 SSc patients were enrolled in our SSc registry. A total of 23 patients received IGU. With a median follow-up of 61 weeks (IQR: 15–82 weeks), the drug persistence was 13/23. In total, 91.3% of the patients (21/23) became free of deterioration in the last visit with IGU. Of note, 10 patients withdrew from the study due to the following reasons: two patients withdrew due to deterioration, three due to incompliance, and five due to mild-to-moderate side effects. All the patients with side effects recovered fully after stopping IGU. Of note, 11 patients had ischemic DU, and 8 out of 11 (72.7%) patients had no new occurrence of DU during the follow-up. In the second cohort of 31 DU patients receiving a combination of vasoactive agents with a median follow-up of 47 weeks (IQR, 16–107 weeks), IGU treatment was protective of new DU occurrence (adjusted risk ratio = 0.25; 95% CI, 0.05–0.94; adjusted odds ratio = 0.07; and 95% CI, 0.01–0.49).

Conclusion

Our study for the first time describes the potential of IGU possibly as an alternative treatment for SSc. To our surprise, this study provides a hint that IGU treatment can be used for the prevention of the occurrence of ischemic DU and merits further investigation.
A practical guide to managing cardiopulmonary toxicities of tyrosine kinase inhibitors in chronic myeloid leukemia
Authors: Kaddoura Rasha , Dabdoob Wafer A. , Ahmed Khalid , Yassin Mohamed A.
Published: May 2023

Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of chronic myeloid leukemia (CML) but their use was associated with a range of serious cardiopulmonary toxicities including vascular adverse events, QT prolongation, heart failure, pleural effusion, and pulmonary arterial hypertension. Dedicated clinical management guidelines for TKI-induced toxicities are not available. This review aims to discuss TKI-associated cardiopulmonary toxicities and proposes a practical guide for their management.