bluuebunny/crossref_metadata_2025 huggingface dataset:
Selecting For Extremists: Evaluating the Impact of Judicial Selection Methods on Ideology
Authors: Parker Brett
Published: September 2022

U.S. states display striking heterogeneity in their choices of judicial selection method. Researchers have produced dozens of papers exploring how the most commonly-used selection methods—partisan election, nonpartisan election, merit selection, and unconstrained gubernatorial appointment—affect the ideology and behavior of the judges they produce. Nevertheless, these articles have studied only a limited set of outcome variables. Most published work concerns either how selection method affects (1) judicial responsiveness to public opinion or (2) ideological direction. To my knowledge, however, no empirical work explores how choice of selection method impacts ideological extremity. This paper fills that gap. Using generalized propensity score matching, fixed effects counterfactual estimators, and synthetic controls to conduct causal inference, I examine whether some methods of selection produce more moderate (or extreme) judges than others. I find consistent evidence that judges picked by unconstrained gubernatorial appointment are more extreme on average than those selected by other methods.
2-Hydroxymethyl-1-methyl-5-nitroimidazole, one siderophore inhibitor, occludes quorum sensing in Pseudomonas aeruginosa
Authors: Yin Lujun , Shen Wang , Liu Jun-Sheng , Jia Ai-Qun
Published: September 2022

Siderophore is necessary for the survival of microorganisms and is interregulated with quorum sensing (QS) systems. It is related to growth, proliferation, virulence, and other bacterial social activities as a virulence factor. Thus, we speculated that the QS system could be occluded by inhibiting siderophore production. 2-Hydroxymethyl-1-methyl-5-nitroimidazole (HMMN), one siderophore inhibitor of Pseudomonas aeruginosa PAO1 (P. aeruginosa PAO1), was obtained by using the Chromeazurol S (CAS) method. We found that HMMN inhibited siderophore production and influenced the biological effects of QS regulation, including biofilm formation and pyocyanin production. HMMN (150 μg/ml) inhibited the siderophore production of P. aeruginosa PAO1 by 69.37%. In addition, HMMN could inhibit pyocyanin production and biofilm formation and erase the formed biofilm of P. aeruginosa PAO1. HMMN (150 μg/ml) inhibited the biofilm formation of P. aeruginosa PAO1 by 28.24%. The erasure rate of the formed biofilm reached 17.03%. Furthermore, HMMN (150 μg/ml) inhibited P. aeruginosa PAO1 pyocyanin production by 36.06%. Meanwhile, positive-control hordenine (500.0 μg/ml) reduced the biofilm formation and pyocyanin production of P. aeruginosa PAO1 by 14.42% and 34.35%, respectively. The erasure rate of hordenine to the formed biofilm is 11.05% at 500 μg/ml. Quantitative real-time polymerase chain reaction (qRT-PCR) showed that HMMN downregulates not only siderophore-related genes but also QS-related genes, as well as hordenine. These results suggest that a siderophore inhibitor could be used as a QS inhibitor to occlude the QS system and reduce virulence.
Toxoplasma gondii infection possibly reverses host immunosuppression to restrain tumor growth
Authors: Chen Jiating , Liao Wenzhong , Peng HongJuan
Published: September 2022

Tumor cells can successfully escape the host immune attack by inducing the production of immunosuppressive cells and molecules, leading to an ineffective tumor treatment and poor prognosis. Although immunotherapies have improved the survival rate of cancer patients in recent years, more effective drugs and therapies still need to be developed. As an intracellular parasite,Toxoplasma gondiican trigger a strong Th1 immune response in host cells, including upregulating the expression of interleukin-12 (IL-12) and interferon-γ (IFN-γ). Non-replicating uracil auxotrophic strains ofT. gondiiwere used to safely reverse the immunosuppression manipulated by the tumor microenvironment. In addition to the whole lysate antigens,T. gondii-secreted effectors, includingToxoplasmaprofilin, rhoptry proteins (ROPs), and dense granule antigens (GRAs), are involved in arousing the host’s antigen presentation system to suppress tumors. WhenT. gondiiinfection relieves immunosuppression, tumor-related myeloid cells, including macrophages and dendritic cells (DCs), are transformed into immunostimulatory phenotypes, showing a powerful Th1 immune response mediated by CD8+T cells. Afterwards, they target and kill the tumor cells, and ultimately reduce the size and weight of tumor tissues. This article reviews the latest applications ofT. gondiiin tumor therapy, including the activation of cellular immunity and the related signal pathways, which will help us understand whyT. gondiiinfection can restrain tumor growth.
In silico characterization of IncX3 plasmids carrying blaOXA-181 in Enterobacterales
Authors: Yu Zhijian , Zhang Zhengrong , Shi Lile , Hua Shengni , Luan Ting , Lin Qiuping , Zheng Zhixiong , Feng Xiaosan , Liu Mubiao , Li Xiaobin
Published: September 2022

Carbapenem-resistant Enterobacterales poses a global urgent antibiotic resistance threat because of its ability to transfer carbapenemase genes to other bacteria via horizontal gene transfer mediated by mobile genetic elements such as plasmids. Oxacillinase-181 (OXA-181) is one of the most common OXA-48-like carbapenemases, and OXA-181-producing Enterobacterales has been reported in many countries worldwide. However, systematic research concerning the overall picture of plasmids harboring blaOXA-181 in Enterobacterales is currently scarce. In this study, we aimed to determine the phylogeny and evolution of blaOXA-181-positive (gene encoding OXA-181) plasmids. To characterize the plasmids harboring blaOXA-181 in Enterobacterales, we identified 81 blaOXA-181-positive plasmids from 35,150 bacterial plasmids downloaded from the NCBI RefSeq database. Our results indicated that diverse plasmid types harbored blaOXA-181 but was predominantly carried by IncX3-type plasmids. We systematically compared the host strains, plasmid types, conjugative transfer regions, and genetic contexts of blaOXA-181 among the 66 blaOXA-181-positive IncX3 plasmids. We found that IncX3 plasmids harboring blaOXA-181 were mostly ColKP3-IncX3 hybrid plasmids with a length of 51 kb each and were mainly distributed in Escherichia coli and Klebsiella pneumoniae. Most of the IncX3 plasmids harboring blaOXA-181 were human origin. Almost all the blaOXA-181-positive IncX3 plasmids were found to carry genes coding for relaxases of the MOBP family and VirB-like type IV secretion system (T4SS) gene clusters, and all the 66 IncX3 plasmids were found to carry the genes encoding type IV coupling proteins (T4CPs) of the VirD4/TraG subfamily. Most IncX3 plasmids harbored both blaOXA-181 and qnrS1 in their genomes, and the two antibiotic resistance genes were found to a composite transposon bracketed by two copies of insertion sequence IS26 in the same orientation. Our findings provide important insights into the phylogeny and evolution of blaOXA-181-positive IncX3 plasmids and further address their role in acquiring and spreading blaOXA-181 genes in Enterobacterales.
Captive diet does not influence exploration behavior upon reintroduction to the wild in a critically endangered amphibian
Authors: Kelleher Shannon R. , Silla Aimee J. , Hunter David A. , McFadden Michael S. , Byrne Phillip G.
Published: September 2022

Exploration behavior can have profound effects on individual fitness. Consequently, knowledge of the proximate mechanisms underpinning exploration behavior may inform conservation breeding programs (CBPs) for threatened species. However, the environmental factors that influence exploration behavior in captivity and during the reintroduction process remain poorly understood. Dietary micronutrients, such as carotenoids, are known to affect the expression of energetically costly behavioral traits, and theoretically may also influence the degree of exploration behavior in various contexts. Here, we investigate whether dietary β-carotene supplementation in captivity influences exploration behavior upon reintroduction to the wild in the critically endangered southern corroboree frog,Pseudophryne corroboree.We conducted a manipulative dietary experiment where captive bredP. corroboreewere supplemented with different doses of β-carotene for 40 weeks prior to release. Frogs (n = 115) were reintroduced to the wild using a soft-release approach, where they were released into field enclosures specifically designed for this species. Upon reintroduction, the frogs’ initial exploration behavior was measured using a standardized behavioral assay. There was no effect of diet treatment on any measure of exploration behavior (mean latency to leave the initial refuge, time spent mobile within the release apparatus and latency to disperse into the field enclosure). However, there was a significant relationship between individual body size and latency to leave the refuge, whereby smaller individuals left the refuge more rapidly. While these findings provide no evidence that β-carotene at the dosages tested influencesP. corroboreeexploration behavior in a reintroduction context, the effect of body size draws attention to the potential for bodily state to influence exploration behavior. We discuss the need for ongoing research investigating the influence of captive diet on post release behavior, and highlight how knowledge concerning state-dependent behavior might help to inform and direct reintroduction programs.
RETRACTED: Prevalence of coronary artery disease and its risk factors in Majmaah City, Kingdom of Saudi Arabia
Authors: Albar Haitham M. , Alahmdi Riyadh Ahmed , Almedimigh Abdulmalik A. , Shaik Riyaz Ahmed , Ahmad Mohammad Shakil , Almutairi Abdulaziz Badar , Alghuyaythat Waleed Khalid Z. , Alaoufi Shouq Yaseen , Aloyari Worud Omar , Alanazi Rand Muslat S.
Published: September 2022

Objective

This study was carried out with an aim to outline the prevalence of coronary artery diseases, its risk of one region of the Saudi Arabia.

Methods

A retrospective observational study conducted across five secondary medical centers located in the city of Majmaah. Hospital medical records and ministry of health records were screened over a 6-month period for data on patients admitted for Coronary artery disease (CAD). Data collected included sociodemographic characteristics, medical profile, and laboratory findings.

Results

A total of 327 participants were included in this study with a median age of 64 and the majority being male participants (59.8%). The majority were married, held a primary school degree and earned a salary for living. A large number (82.9%) were hypertensive and diabetic (66.7%) and one-fourth had a previous MI (25.1%). A large number (73.7%) had heart failure with a mean ejection fraction of 44% (SD = 13). The causes of heart failure were mainly ischemic (56.3%) and hypertensive (28.1%). Readmission rates at 30 and 90 days then at 6 and 12 months were 22, 53.8, 68.8, and 75.8%, respectively. The mortality rates at the same time intervals were 5.5, 8.9, 14.1, and 22.9%, respectively. Predictors of readmission are age, CCI, and NYHA class.

Conclusion

Coronary artery disease is the leading cause of heart failure. End stage CAD can have similar results in terms of readmission and mortality as heart failure. Future research should target patients in different stages of the condition and monitor their comorbidities which may impact the study findings.
Hyperglycemia may increase deep vein thrombosis in trauma patients with lower limb fracture
Authors: Liu Xiaojie , Li Tiajun , Xu Hui , Wang Chunhua , Ma Xiaojun , Huang Hui , Hu Yanling , Chu Haichen
Published: September 2022

Diabetes mellitus is associated with prothrombotic states and thrombotic events. This study examined the association between preoperative glucose levels and deep vein thrombosis (DVT) in trauma patients undergoing surgery for lower limb fracture. Data from 1,591 patients who underwent fracture surgery between January 2017 and March 2022 at the Affiliated Hospital of Qingdao University were queried from institutional electronic medical records. A total study population of 1,086 patients was identified, comprising 138 patients who experienced DVT and 948 controls. The primary outcome was DVT. Multiple logistic regression analyses were performed and a receiver operating characteristic (ROC) curve was generated. Age, D-dimer level, preoperative RBC count, and preoperative glucose level were independent predictors of DVT. The two highest categories of D-dimer level (≥ 960, < 2,102; ≥ 2,102 ng/ml) increased the odds ratio for DVT by 4.215 times [95% confidence interval (CI) 1.820–9.761] and 7.896 times (95% CI 3.449–18.074), respectively, compared with the lowest reference category (< 490 ng/ml). The area under the curve (AUC) for the preoperative glucose level was 0.605. Hyperglycemia (glucose ≥ 6.1, < 7.0 mmol/l) increased the odds of DVT by 1.889-fold [95% CI (1.085–3.291); p < 0.0001] compared with euglycemia (glucose < 6.1 mmol/l). We therefore observed an association between preoperative hyperglycemia and DVT in patients with lower limb fractures. There are several modalities for controlling hyperglycemia, offering potential targets for future improvement.
Bioresorbable scaffolds vs. drug-eluting stents on short- and mid-term target lesion outcomes in patients after PCI: A systematic review and meta-analysis
Authors: Wan Yan-di , Wang Da-yang , Deng Wen-qi , Lai Si-jia , Wang Xian
Published: September 2022

Background

While current concerns about bioresorbable scaffolds (BRS) are centered on late or very late scaffold thrombosis, less attention had been paid to short- and mid-term clinical outcomes. This review aimed to compare the short- and mid-term outcomes between BRS and drug-eluting stents (DES).

Methods

A systematic review of randomized controlled trials (RCTs) that compared BRS vs. DES was conducted by searching PubMed, Cochrane Library, Web of Science, CNKI, WanFang, and VIP databases from inception until 19 April 2022 (language limited to English or Chinese). The primary outcome was target lesion failure (TLF) within 12 months, defined as a composite of target lesion revascularization (TLR), target vessel myocardial infarction (TVMI), and cardiac death. The secondary outcomes were in-stent diameter stenosis (DS%) provided by intraluminal imaging.

Results

A total of 13 studies were eligible and were included in this review (N = 9,702 patients). The follow-up duration ranged from 6 months to 1 year. A significantly higher rate of TLF [RR, 1.22, 95% CI (1.03, 1.44)] driven by the higher rate of TVMI [RR, 1.39, 95% CI (1.09, 1.76)] was observed in the BRS group than in the DES group. The risk of TLR and cardiac death was similar between the groups. Also, compared with the DES group, the BRS group had a significantly higher in-stent DS% within 1 year [MD = 5.23, 95%CI (3.43, 7.04); I2 = 97%; p < 0.00001].

Conclusion

Bioresorbable scaffolds were associated with an increased risk of target lesion failure within 1 year as compared with DES, driven by the increased rates of target vessel myocardial infarction. Also, the in-stent DS% seemed to be higher with BRS. Therefore, BRS was inferior to DES in terms of target lesion outcomes at short- or mid-term follow-up.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=327966, PROSPERO (CRD42022327966).
Alprostadil vs. isosorbide dinitrate in ameliorating angina episodes in patients with coronary slow flow phenomenon: A randomized controlled trial
Authors: Zhang Weifeng , Dai Jinjie , Shen Lan , Jiang Yue , Zheng Xiaowen , Xu Ke , Yang Xiaoxiao , Wang Xiaolei , Hao Ziyong , Zhao Yu , Wang Dong , Jiang Lisheng , Qiu Xingbiao , Shen Linghong , He Ben
Published: September 2022

Background

The optimum therapy for coronary slow flow phenomenon (CSFP) stays debatable. This study compared the effectiveness of alprostadil with isosorbide dinitrate in alleviating angina episodes in CSFP patients.

Methods

In this prospective, randomized controlled study, 102 patients with CSFP without severe coronary artery stenosis that exhibited stable angina were allocated randomly in a ratio of 1:1 to either the alprostadil group (40 μg, three times per day, n = 51) or the isosorbide dinitrate group (5 mg, three times per day, n = 51). Frequency of angina events, intensity of suffering, and the Canadian Cardiovascular Society (CCS) grading of angina pectoris were evaluated at baseline and one month after. Additionally, the Seattle Angina Questionnaire (SAQ) was assessed.

Results

Baseline characteristics were comparable between the two groups. At 1-month follow-up, patients administered with alprostadil experienced fewer angina episodes [episodes per week, 1 (2) vs. 2 (2), P < 0.001] and less pain intensity [self-evaluated pain score, 2 (3) vs. 3 (4), P < 0.001] than those with isosorbide dinitrate. In the alprostadil group, 78.4% of patients were classified as CCS class I, significantly higher than the 47.1% seen in the isosorbide dinitrate group (P = 0.001). Furthermore, treatment of alprostadil led to a significant improvement in the SAQ score (7.09 U, 95% CI: 4.22–9.96, P < 0.001) compared to isosorbide dinitrate. Additionally, fewer patients suffered headaches when receiving alprostadil (7.8% vs. 19.6%, P = 0.084).

Conclusion

Alprostadil was more effective in ameliorating angina symptoms in CSFP patients than isosorbide dinitrate.

Clinical trial registration

[www.chictr.org.cn], identifier [ChiCTR2000033233].
Obesity increases cardiovascular mortality in patients with HFmrEF
Authors: Liu Zhican , Peng Yiqun , Zhao Wenjiao , Zhu Yunlong , Wu Mingxin , Huang Haobo , Peng Ke , Zhang Lingling , Chen Sihao , Peng Xin , Li Na , Zhang Hui , Zhou Yuying , Chen Yongliang , Xiao Sha , Fan Jie , Zeng Jianping
Published: September 2022

Background

High body mass index increases the risk of heart failure morbidity and mortality. It is unclear whether a high body mass index is associated with prognosis in patients with heart failure with mildly reduced left ventricular ejection fraction (HFmrEF). We retrospectively analyzed the effect of a high body mass index on the prognosis of patients with HFmrEF.

Methods

We investigated the association between body mass index and cardiovascular death (death from any cardiovascular mechanism) in 1,691 HFmrEF patients (mean age, 68 years; 35% female) in Xiangtan Central Hospital. Using Cox proportional hazards models, body mass index was assessed as a continuous and a categorical variable.

Results

Cardiovascular death occurred in 133 patients (82 males and 51 females) after 1 year of follow-up. After adjustment for established risk factors, there was a 7.5% increase in the risk of cardiovascular death for females for each increment of 1 in BMI. In contrast, changes in male body mass index were not significantly associated with cardiovascular death (P = 0.097). Obese subjects had a 1.8-fold increased risk of cardiovascular death compared with subjects with a normal body mass index. The hazard ratio for females was 2.163 (95% confidence interval: 1.150–4.066). Obesity was not significantly associated with cardiovascular death in males (P = 0.085).

Conclusion

An increased body mass index is associated with an increased risk of cardiovascular death in patients with HFmrEF; however, this risk was mainly associated with female patients with HFmrEF and less with male patients with HFmrEF.
Topical ophthalmic administration: Can a drug instilled onto the ocular surface exert an effect at the back of the eye?
Authors: del Amo Eva M.
Published: September 2022

Topical ophthalmic instillation is an appealing strategy to deliver drugs to the back of the eye to treat retinal diseases such as neovascular age-related macular degeneration, diabetic retinopathy, retinal vein occlusion, and glaucomatous optic neuropathy. It has several advantages such as being non-invasive and user-friendly, e.g., allowing self-administration. However, the main obstacle has been how to achieve therapeutic drug concentrations in the retina due to the eye’s protective mechanisms, flows, and barriers. Less than 4% of the instilled drug dose enters the anterior chamber, and much less is expected to reach the posterior segment. It is crucial to understand a drug’s topical pharmacokinetics in humans and how one can extrapolate data from rabbits to humans. In this review, the available data on the retina and vitreous drug concentrations from pharmacokinetics studies conducted in human patients and rabbits have been compiled, together with the critical physiological factors to be considered for this route of administration. Improvements in the design of preclinical studies are suggested to increase their translatability to the treatment of human patients. Finally, the current status of clinical trials with topical ophthalmic formulations intended to treat the back of the eye is depicted. At present, no topical ophthalmic formulations to treat neovascular age-related macular degeneration or other retinal neurodegenerative illnesses have reached the market.
Hydrogeochemical characteristics of thermal springs in the Qilian–Haiyuan fault zone at the northeast Tibetan Plateau: Role of fluids and seismic activity
Authors: Li Chenhua , Zhou Xiaocheng , Li Jingchao , Liu Lei , Su Hejun , Li Ying , He Miao , Dong Jinyuan , Tian Jiao , Zhou Huiling , Gao Gang , Zhang Caiyan , Luo Zhixin
Published: September 2022

The Qilian–Haiyuan fault zone (QHF) is located in a highly deformed and seismically active area of the northeastern margin of the Tibetan Plateau. This study investigated the major elements, strontium, hydrogen, and oxygen isotopes of 22 sites in the thermal springs along the QHF from October to November 2020. The QHF hydrochemical system is recharged by meteoric water primarily infiltrating between 2.8 and 4.4 km a.s.l. Based on quartz geothermometers, the geothermal reservoir temperature variation ranged from 25.5 to 111.3°C, and the circulation depth ranged from 1.3 to 5.6 km. In the QHF zone, the highest spring water temperature values were correlated with deep groundwater circulation circuits in areas where earthquake foci are concentrated. A conceptual model of the hydrologic cycle of thermal springs explains the spatial distribution of earthquakes associated with tectonic movements. The fluid circulation of the QHF corresponds well with the seismicity, which indicates that the hydrological characteristics of the thermal spring in a fault zone are vital in receiving information on seismic activity to assess the seismic risk of the QHF in the future.
Crustal permeability changes inferred from seismic attenuation: Impacts on multi-mainshock sequences
Authors: Malagnini Luca , Parsons Tom , Munafò Irene , Mancini Simone , Segou Margarita , Geist Eric L.
Published: September 2022

We use amplitude ratios from narrowband-filtered earthquake seismograms to measure variations of seismic attenuation over time, providing unique insights into the dynamic state of stress in the Earth’s crust at depth. Our dataset from earthquakes of the 2016–2017 Central Apennines sequence allows us to obtain high-resolution time histories of seismic attenuation (frequency band: 0.5–30 Hz) characterized by strong earthquake dilatation-induced fluctuations at seismogenic depths, caused by the cumulative elastic stress drop after the sequence, as well as damage-induced ones at shallow depths caused by energetic surface waves. Cumulative stress drop causes negative dilatation, reduced permeability, and seismic attenuation, whereas strong-motion surface waves produce an increase in crack density, and so in permeability and seismic attenuation. In the aftermath of the main shocks of the sequence, we show that theM≥ 3.5 earthquake occurrence vs. time and distance is consistent with fluid diffusion: diffusion signatures are associated with changes in seismic attenuation during the first days of the Amatrice, Visso-Norcia, and Capitignano sub-sequences. We hypothesize that coseismic permeability changes create fluid diffusion pathways that are at least partly responsible for triggering multi-mainshock seismic sequences. Here we show that anelastic seismic attenuation fluctuates coherently with our hypothesis.
Remote sensing image classification based on object-oriented convolutional neural network
Authors: Liu Fangjian , Dong Lei , Chang Xueli , Guo Xinyi
Published: September 2022

Remote sensing image classification is of great importance for urban development and planning. The need for higher classification accuracy has led to improvements in classification technology. In this research, Landsat 8 images are used as experimental data, and Wuhan, Chengde and Tongchuan are selected as research areas. The best neighborhood window size of the image patch and band combination method are selected based on two sets of comparison experiments. Then, an object-oriented convolutional neural network (OCNN) is used as a classifier. The experimental results show that the classification accuracy of the OCNN classifier is 6% higher than that of an SVM classifier and 5% higher than that of a convolutional neural network classifier. The graph of the classification results of the OCNN is more continuous than the plots obtained with the other two classifiers, and there are few fragmentations observed for most of the category. The OCNN successfully solves the salt and pepper problem and improves the classification accuracy to some extent, which verifies the effectiveness of the proposed object-oriented model.
Electromagnetic transient characteristics and overvoltage suppression strategy of renewable energy-oriented power system connected by gas-insulated transmission lines
Authors: Yang Guang , Zhu Yong , Zen Fanxing , Zhou Shengzhi , Chen Yuhang
Published: September 2022

New energy systems, such as wind power and photovoltaic and distributed power supply, in the power generation and grid-connected transmission system basically will use stronger insulation design, higher operational safety, and smaller footprint GIL equipment, while the new energy transmission system of the smart grid development trend requires accompanying the electronic transformer equipment to promote a large area. However, the current GIL equipment used in new energy transmission systems has caused great electromagnetic interference to the electronic equipment due to the compact layout of the equipment and the transient signals generated by normal operation, which has seriously restricted the development of smart grids and became a major obstacle to the grid connection of new energy systems. In order to study the characteristics and developmental law of transient electromagnetic interference signal of GIL equipment in new energy transmission and transformation system, this study proposes a dynamic arc model based on an optimized arc extinguishing criterion, verifies the correctness of the improved dynamic arc model through theoretical analysis, simulates calculation combined with the test measurement data, and compares and analyzes the simulation results with test measurement data to study the transient electromagnetic interference source signal during arc burning duration. The simulation results and test data are compared and analyzed to study the pulse steepness, size of the wave head, and overall waveform development law of the transient electromagnetic interference source signal during the arc burning process. It is concluded that the dynamic arc model based on the optimized arc extinguishing criterion can be better used to study the transient electromagnetic interference signal in the GIL equipment. Meanwhile, the transient electromagnetic interference signal has the characteristics of large amplitude and high frequency, the maximum overvoltage can reach 1.9 p.u., the UHF can reach 30 MHz, and the wave head rise time is about 12 ns. This study provides theoretical support for subsequent research on suppressing transient electromagnetic interference source signals, improving the anti-electromagnetic interference performance of electronic devices, and is dedicated to solving the obstruction problem in the process of grid connection of new energy transmission and substation systems.
LY6G6D is a selectively expressed colorectal cancer antigen that can be used for targeting a therapeutic T-cell response by a T-cell engager
Authors: Corrales Leticia , Hipp Susanne , Martin Katharina , Sabarth Nicolas , Tirapu Iñigo , Fuchs Klaus , Thaler Barbara , Walterskirchen Christian , Bauer Kathrin , Fabits Markus , Bergmann Michael , Binder Carina , Chetta Paolo ML. , Vogt Anne B. , Adam Paul J.
Published: September 2022

Colorectal cancer (CRC) is one of the most common cancers worldwide and demands more effective treatments. We sought to identify tumor selective CRC antigens and their therapeutic potential for cytotoxic T-cell targeting by transcriptomic and immunohistochemical analysis. LY6G6D was identified as a tumor selectively expressed CRC antigen, mainly in the microsatellite stable (MSS) subtype. A specific anti LY6G6D/CD3 T cell engager (TcE) was generated and demonstrated potent tumor cell killing and T cell activation in vitro. Ex vivo treatment of primary patient-derived CRC tumor slice cultures with the LY6G6D/CD3 TcE led to IFNγ secretion in LY6G6D positive tumor samples. In vivo, LY6G6D/CD3 TcE monotherapy demonstrated tumor regressions in pre-clinical mouse models of engrafted human CRC tumor cells and PBMCs. Lastly, 2D and 3D cocultures of LY6G6D positive and negative cells were used to explore the bystander killing of LY6G6D negative cells after specific activation of T cells by LY6G6D positive cells. LY6G6D/CD3 TcE treatment was shown to lyse target negative cells in the vicinity of target positive cells through a combined effect of IFNγ, TNFα and Fas/FasL. In summary, LY6G6D was identified as a selectively expressed CRC antigen that can be utilized to potently re-direct and activate cytotoxic T-cells to lyse LY6G6D expressing CRC using a TcE. This effect can be spread to target negative neighboring tumor cells, potentially leading to improved therapeutic efficacy.
Immune status for monitoring and treatment of bladder cancer
Authors: Pan Shen , Li Shijie , Zhan Yunhong , Chen Xiaonan , Sun Ming , Liu Xuefeng , Wu Bin , Li Zhenhua , Liu Bitian
Published: September 2022

The high recurrence rate of non-muscle invasive bladder cancer (BC) and poor prognosis of advanced BC are therapeutic challenges that need to be solved. Bacillus Calmette-Guerin (BCG) perfusion was the pioneer immunotherapy for early BC, and the discovery of immune checkpoint inhibitors has created a new chapter in the treatment of advanced BC. The benefit of immunotherapy is highly anticipated, but its effectiveness still needs to be improved. In this review, we collated and analysed the currently available information and explored the mechaisms by which the internal immune imbalance of BC leads to tumour progression. The relationship between immunity and progression and the prognosis of BC has been explored through tests using body fluids such as blood and urine. These analytical tests have attempted to identify specific immuyne cells and cytokines to predict treatment outcomes and recurrence. The diversity and proportion of immune and matrix cells in BC determine the heterogeneity and immune status of tumours. The role and classification of immune cells have also been redefined, e.g., CD4 cells having recognised cytotoxicity in BC. Type 2 immunity, including that mediated by M2 macrophages, Th2 cells, and interleukin (IL)-13, plays an important role in the recurrence and progression of BC. Pathological fibrosis, activated by type 2 immunity and cancer cells, enhances the rate of cancer progression and irreversibility. Elucidating the immune status of BC and clarifying the mechanisms of action of different cells in the tumour microenvironment is the research direction to be explored in the future.
Red blood cell transfusions impact response rates to immunotherapy in patients with solid malignant tumors
Authors: Mispelbaum Rebekka , Hattenhauer Sandra Tessa , Brossart Peter , Heine Annkristin
Published: September 2022

Red blood cell (RBC) transfusions have been shown to exert immunosuppressive effects in different diseases. In consequence, RBC transfusions might also negatively influence the response to immunotherapeutic treatment approaches. To address how RBC transfusions impact response rates of antitumor immunotherapy (IT), we conducted a retrolective clinical study of patients with different solid tumors treated with IT (atezolizumab, pembrolizumab, nivolumab and/or ipilimumab). We assessed the number of RBC concentrates received within 30 days before and 60 days after the start of IT. Primary objective was the initial therapy response at first staging, secondary objectives the number of immune related adverse events and infections. 15 of 55 included patients (27.3%) received RBC concentrates. The response rates were 77.5% in the non-transfused (n=40) versus 46.7% in the transfused patient group (n=15) and reached statistical significance (p=0.047). The correlation between therapy response and transfusion was statistically significant (p=0.026) after adjustment for the only identified confounder “line of therapy”. In contrast, transfusion in the interval 30 days before IT showed no significant difference for treatment response (p=0.705). Moreover, no correlation was detected between RBC transfusion and irAE rate (p=0.149) or infection rate (p=0.135). In conclusion, we show for the first time that the administration of RBC transfusions during, but not before initiation of IT treatment, negatively influences the response rates to IT. Our findings suggest a restrictive transfusion management in patients undergoing IT to receive optimal response rates.
The effect of serum IL-2 levels on the prognosis of primary biliary cholangitis-related liver failure and the preliminary exploration of its mechanism
Authors: Wang Qi , Wang Yang , Qiao Wenying , Xu Bin , Liu Yanmin , Zhang Xiaodan , Li Wenjuan , Zhao Juan , Liu Mengcheng , Zhang Yang , Chen Dexi , Huang Chunyang , Jin Ronghua
Published: September 2022

Background

In primary biliary cholangitis (PBC), the levels of serum IL-2 were involved in liver inflammation and immune changes. This study aimed to investigate the prognostic significance of serum IL-2 combined with total bilirubin (TBIL) in liver failure and cytokine changes during the disease.

Methods

A total of 160 PBC patients treated with UDCA were included. Parameters at admission were collected, and the COX regression model was used to predict independent risk factors associated with PBC disease progression. We identified the optimal cut-off values and prognosis effects of serum IL-2 and TBIL based on the time-dependent receiver operating characteristic (ROC) curve. We also analyzed the incidence of liver failure with Kaplan-Meier survival analysis. In addition, the changes of cytokines (mainly IL-2) in liver tissues and blood samples from 11 patients with end-stage PBC liver failure and five healthy controls were examined.

Results

Age, IL-2, ALB, γ-GT, ALP, TBIL, Hb, TBA, WBC, and PLT, as well as anti-Sp100, were found to be independent risk factors in PBC patients with liver failure. Patients with decreased serum IL-2 levels and increased TBIL levels have a significantly higher incidence of liver failure and a worse prognosis. Patients with advanced PBC liver failure after liver transplantation exhibited a significant decrease in levels of serum IL-2 and a relatively immunosuppressed status.

Conclusions

The combination of serum IL-2 and TBIL can be a predictor of the progression of liver failure in patients with primary biliary cholangitis, and it is likely to be related to the expression of GM-CSF and G-CSF.
Depositional control on the sulfur content and isotope of sedimentary pyrite from the southeast coast of China since MIS5
Authors: Chang Xin , Liu Xiting , Wang Houjie , Zhuang Guangchao , Ma Zhixin , Yu Junjie , Chen Jing
Published: September 2022

The content and isotopic composition of pyrite sulfur are significantly affected by local depositional conditions and are sensitive to environmental evolution. Here, we use core QK11, collected from Xiapu Bay, southeast coast of China, to reveal how local depositional conditions constrained pyrite formation and sulfur isotopic composition since MIS5. Our results show that the content of pyrite sulfur is mainly controlled by the TOC content during interglacial intervals and is limited by the supplement of sulfate in glacial intervals. Therefore, the C/S ratios can effectively identify three transgressions since MIS5. The sulfur isotopic composition of pyrite ranges from -36.7 to 18.4‰ in the whole core. The occurrence of isotopically “heavy” pyrite is observed at the depth of 2.2~9.2, 27.2~33.8, and 43.5~62.5 mbsf, which is attributed to the influence of sulfate reservoir effect, depositional event, unsteady diagenetic environment, and other factors, highlighting the influence of local depositional and diagenetic processes on the isotopic composition of pyrite sulfur. Pyrite sulfur in other layers is generally depleted in 34S, as low as -36.7‰, indicating that the early-stage organiclastic sulfate reduction (OSR) plays an important role in sulfur isotopic fractionation. The results also suggest that organic carbon indicators (TOC/TN ratio and δ13C) combined with the C/S ratio can effectively distinguish between freshwater and marine environments, which is of great significance to reveal depositional evolution in deep time.
Giant kelp genetic monitoring before and after disturbance reveals stable genetic diversity in Southern California
Authors: Klingbeil William H. , Montecinos G. J. , Alberto Filipe
Published: September 2022

Given the impacts of climate change and other anthropogenic stressors on marine systems, there is a need to accurately predict how species respond to changing environments and disturbance regimes. The use of genetic tools to monitor temporal trends in populations gives ecologists the ability to estimate changes in genetic diversity and effective population size that may be undetectable by traditional census methods. Although multiple studies have used temporal genetic analysis, they usually involve commercially important species, and rarely sample before and after disturbance. In this study, we run a temporal analysis of giant kelp, Macrocystis pyrifera, genetic diversity over the scope of 10 years (2008-2018) using the same microsatellite marker panel to assess the genetic consequences of disturbance in several populations of giant kelp (Macrocystis pyrifera) in the Southern California Bight. The study is a rare pre- and post-disturbance microsatellite analysis that included declines to giant kelp caused by the 2015/16 El Nino Southern Oscillation event. We used canopy biomass estimated by remote sensing (Landsat) to quantify the extent of disturbance to kelp beds, and sea surface temperature data to understand how kelp was pushed towards its temperature limits during this period. Despite prolonged periods with decreased canopy at several sites, no changes in genetic structure and allelic richness were observed. We argue that giant kelp in the region is best described as a “patchy population” system where true extinctions are rare. We discuss how deep refugia of subsurface sporophytes and cryptic microscopic life stages could have kept genetic diversity through disturbance. Given the increasing effects of climate change and uncertainty in modeling impacts of species with cryptic life history stages, we suggest further investigation to reveal the role such stages play in species resilience. Genetic monitoring studies of sites selected by remote census demographic and climate surveys should be continued in the future given the predicted impacts of climate change.
Horizontal and vertical heterogeneity of sediment microbial community in Site F cold seep, the South China Sea
Authors: Zhai Xinyi , Shi Xiaochong , Cheng Haojin , Yao Peng , Zhao Bin , Chen Lin , Liu Jiwen , Cao Lei , Wang Minxiao , Fu Lulu , Zhang Xiao-Hua , Yu Min
Published: September 2022

Site F is the most vigorous cold seep known on the continental slope of the northern South China Sea. Up to now, the microbial community structures in sediments of Site F based on the high-throughput sequencing of the 16S rRNA genes have been studied extensively. However, few studies investigated the microbial community structures at fine vertical scales of Site F and control stations outside Site F. In this study, a comprehensive investigation of microbial communities in sediments of Site F along the depths varying from 0 to 24 cm below sea floor (cmbsf) of four sampling sites—SRS (Southern Reduced Sediment), NRS (Northern Reduced Sediment), Control 1 (close to Site F), and Control 2 (far from Site F)—was carried out. The high relative abundances of anaerobic methanotrophic archaea (ANME),Desulfobacterota[sulfate-reducing bacteria (SRB)], andCampylobacteria[sulfur-oxidizing bacteria (SOB)] in SRS and NRS indicated that these two sites were newborn cold seep sites compared with non-seep sites, Control 1, and Control 2. A positive correlation between ANME-1b, ANME-2, and SEEP-SRB and an enrichment ofSulfurovumandMethlomonadaceaewere found in the surface sediments of both SRS and NRS, indicating that the processes of anaerobic oxidation of methane (AOM), sulfur oxidation, and sulfate reduction might occur in seep sites. SRS was enriched with ANME-1b and SEEP-SRB2 with a proposed sulfate-methane transition zone (SMTZ) approximately located at 8 cmbsf. The high abundance of ANME in SRS may due to the high concentration of methane. NRS was enriched with ANME-2,Desulfatiglans,Sulfurovum, andMethanosarcinaceaewith a proposed SMTZ at about 10 cmbsf. According to the analyses of microbial community structure and environmental factors, NRS could be described as a notable cold seep reduced sediment site with low sulfate and high H2S that nourished abundant SEEP-SRB1, ANME-2,Methanosarcinales, andSulfurovum, which showed similar distribution pattern. Our study expands the current knowledge on the differences of microbial communities in cold seep sites and non-seep sites and sheds light on the horizontal and vertical heterogeneity of sediment microbial community in Site F.
Erosion of carbonate-bearing sedimentary rocks may close the alkalinity budget of the Baltic Sea and support atmospheric CO2 uptake in coastal seas
Authors: Wallmann Klaus , Diesing Markus , Scholz Florian , Rehder Gregor , Dale Andrew W. , Fuhr Michael , Suess Erwin
Published: September 2022

High alkalinity values observed in coastal seas promote the uptake of CO2 from the atmosphere. However, the alkalinity budget of coastal areas and marginal seas is poorly understood, even though some of the recently observed alkalinity enhancement can be ascribed to riverine fluxes and anaerobic processes in shelf sediments. Here, we investigate the alkalinity budget of the Baltic Sea to identify previously unrecognized alkalinity sources. We quantify the generation of alkalinity and dissolved calcium (Ca) in this marginal sea applying simple mass balance calculations. Using this approach, we identify alkalinity and Ca sources of approximately 324 Gmol yr-1 and 122 Gmol yr-1, respectively, that cannot be ascribed to the riverine input. The magnitude of the Ca source suggests that a major fraction of the excess alkalinity (244 Gmol yr-1) is induced by the dissolution of calcium carbonate (CaCO3). A review of available field data shows that carbonate-bearing rocks at the coast and the seabed of the Baltic Sea are rapidly eroded and may provide sufficient CaCO3 to close the Ca budget. Hence, dissolution of eroded CaCO3 is the most likely source for the Ca enrichment observed in Baltic Sea water. This hypothesis is supported by mass accumulation rates of sediments derived from radioisotope data that are evaluated to derive a basin-wide rate of mud to muddy sand accumulation at the bottom of the Baltic Sea. The resulting value (139 Tg yr-1) exceeds current estimates of riverine particle fluxes into the Baltic Sea by more than one order of magnitude and confirms that rates of till erosion are sufficiently high to account for the Ca and most of the alkalinity excess in Baltic Sea water. Finally, we show that deliberate addition of CaCO3 to sediments deposited in the Baltic Sea could neutralize significant amounts of CO2 and help to achieve net-zero greenhouse gas emissions in the Baltic region.
Poor pulmonary health in Barataria Bay dolphins in the eight years following the Deepwater Horizon oil spill
Authors: Smith Cynthia R. , Rowles Teresa K. , Gomez Forrest M. , Ivančić Marina , Colegrove Kathleen M. , Takeshita Ryan , Townsend Forrest I. , Zolman Eric S. , Morey Jeanine S. , Cendejas Veronica , Meegan Jennifer M. , Musser Whitney , Speakman Todd R. , Barratclough Ashley , Wells Randall S. , Schwacke Lori H.
Published: September 2022

TheDeepwater Horizon(DWH) disaster resulted in large-scale contamination of bays, sounds, and estuaries in the northern Gulf of Mexico, home to multiple stocks of common bottlenose dolphins (Tursiops truncatus). Inhalation, aspiration, ingestion, and dermal absorption of oil and its toxic components were all considered possible routes of exposure for dolphins living within the oil spill footprint. To determine if dolphins were adversely impacted, catch-and-release health assessments were performed in heavily-oiled Barataria Bay (BB), Louisiana, and in Sarasota Bay (SB), Florida, a comparison site with no DWH oil contamination. Initial studies were conducted as part of a Natural Resource Damage Assessment (2011-2014) and follow-on studies were performed between 2016-2018 with support from the Gulf of Mexico Research Initiative. Ultrasound was used to evaluate the dolphins’ pulmonary health, including the presence/absence of pleural effusion, nodules, masses, consolidation, and alveolar interstitial syndrome (AIS). When present, AIS was further graded by severity (mild, moderate, or severe) and distribution. Based on the presence and severity of abnormalities, each dolphin was given an overall lung disease score (normal, mild, moderate, or severe). Normal to mild scores were considered within expected limits for a wild population, therefore the prevalence of normal-mild versus moderate-severe scores was compared between the oiled and unoiled sites. Separate analyses were conducted for dolphins alive in 2010 (and in BB, presumably exposed to DWH oil), and those born after 2010. For the dolphins alive in 2010, temporal trends were also examined using generalized additive models (GAMs). Results showed a strong difference (p=0.000357) in moderate to severe lung disease between the two sites for dolphins alive in 2010, but no significant difference (p=0.6745) between the sites for dolphins born after 2010. In BB dolphins, the prevalence of moderate to severe lung disease did not decrease in the years after the spill, and in fact, potentially worsened (p=0.0644 for trend over years), with the highest prevalence (0.61) being in 2018. Moderate to severe AIS remained a persistent finding in BB dolphins, and several animals had a pattern of AIS that was more severe ventrally than dorsally, with evidence of chronic, progressive disease states.