bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of advanced liver fibrosis on atrial fibrillation recurrence after ablation in non-alcoholic fatty liver disease patients
Authors: Wang Zhe , Wang Yijia , Luo Fangyuan , Zhai Yafei , Li Jiaju , Chen Yinong , Li Qing , Zhu Longyang , Jiao Siqi , Liu Peng , Zhou Yifeng , Chen Yingwei , Dong Jianzeng , Sun Yihong
Published: October 2022

Aim

Advanced liver fibrosis is independently associated with new onset of atrial fibrillation (AF). Non-invasive liver fibrosis scores are considered an effective strategy for assessing liver fibrosis. This study aimed to investigate the association between advanced liver fibrosis and AF recurrence after ablation in patients with non-alcoholic fatty liver disease (NAFLD).

Materials and methods

A total of 345 AF patients with NAFLD who underwent de novo ablation between 2019 and 2020 at two large hospitals in China were included in this study. AF recurrence was defined as the occurrence of atrial arrhythmia for more than 30 s by electrocardiogram or 24 h Holter monitoring after the first 3 months of ablation. Predictive values of non-alcoholic fatty liver disease fibrosis score (NFS) and Fibrosis-4 (FIB-4) scores for AF burden and recurrence after ablation were assessed.

Results

At the 1 year follow-up after ablation, 38.8% of patients showed recurrence. Patients with recurrence who had higher FIB-4 and NFS scores were more likely to have persistent AF and a duration of AF ≥ 3 years. In Kaplan–Meier analysis, patients with intermediate and high NFS and FIB-4 risk categories had a higher risk of AF recurrence. Compared to patients with the low risk, intermediate and high NFS, and FIB-4 risk were independently associated with AF recurrence in multivariate Cox regression analysis (high risk: NFS, hazard ratio (HR): 3.11, 95% confidence interval (CI): 1.68∼5.76, p < 0.001; FIB-4, HR: 3.91, 95% CI: 2.19∼6.98, p < 0.001; intermediate risk: NFS, HR: 1.85, 95% CI: 1.10∼3.10, p = 0.020; FIB-4, HR: 2.08, 95% CI: 1.27∼3.41, p = 0.003).

Conclusion

NFS and FIB-4 scores for advanced liver fibrosis are associated with AF burden. Advanced liver fibrosis is independently associated with AF recurrence following ablation. Advanced liver fibrosis might be meaningful in risk classification for patients after AF ablation.
Rs420137, rs386360 and rs7763726 polymorphisms in fibronectin type III domain containing 1 are associated with susceptibility to coronary heart disease: Analysis in the Han population
Authors: He Xiaodan , Li Xuemei , Du Xiaoyan , Han Jianlun , Zhang Hui , Zhu Yan , Ma Honghong
Published: October 2022

Background

Numerous genetic studies have shown that genes are related to the pathogenesis of coronary heart disease (CHD). The main aim of this study was to confirm whether fibronectin type III domain containing 1 (FNDC1) polymorphisms correlate with the risk of CHD.

Methods

In this study, in order to assess the association between three FNDC1 single nucleotide polymorphisms (SNPs) and the risk of CHD, we conducted a case-control study involving 630 patients with CHD and 568 healthy controls using Agena MassARRAY (Agena Bioscience, San Diego, CA, USA). Genotype distribution in case and control groups was analyzed by Chi square test. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression models adjusted for age, sex, smoking, and alcohol consumption to assess the correlation between SNPs and CHD risk.

Results

Our results indicated that FNDC1-rs420137, -rs386360, and -rs7763726 played important roles in enhancing the risk of CHD. Subgroup analysis revealed that rs420137 increased the susceptibility to CHD in males, smokers, and patients aged ≤62 years. Rs360 had an increased risk of CHD in males, patients at aged ≤62 years, smokers, and non-drinkers. Furthermore, the association of rs7763726 with increased CHD risk was also observed in males, patients aged ≤62 years, smokers, and drinkers. Last but not least, these three SNPs we selected were protective factors against hypertension in CHD individuals.

Conclusion

Our research suggest that FNDC1-rs420137, -rs386360, and -rs7763726 variants may be regarded as novel biomarkers for predicting CHD risk and other specific mechanisms of action of CHD need to be further studied.
Effect of radiotherapy on cardiac-specific death in patients with non-malignant tumors of central nervous system and related clinical features
Authors: Wang Ruxin , Ye Haowen , Zhao Yongting , Ma Li , Wei Jinjing , Wang Ying , Zhang Xiaofang , Wang Lihong
Published: October 2022

Importance

Cardiac-specific death from radiation caused by radiation therapy (RT) in patients with malignant tumors has received extensive attention, however, little is known regarding the potential cardiotoxic effects of RT in patients with non-malignant tumors.

Objectives and methods

In this study, we used the SEER data to explore the incidence of post-radiation cardiovascular complications in patients with non-malignant tumors of central nervous system (CNS), and identify the influencing factors of cardiac-specific death.

Results

Ultimately 233, 306 patients were included (97.8% of patients had brain tumors and 2.2% had spinal cord tumors). For patients with non-malignant tumors of CNS, RT {yes (odds ratio [OR] 0.851, 95% confidence interval [CI] 0.774–0.936, p = 0.001, before propensity score matching (PSM); OR 0.792, 95% CI 0.702–0.894, p < 0.001, after PSM) vs. no} was associated with lower risk of cardiac-specific death, other clinical features affecting cardiac death similar to those in patients with non-malignant tumors of CNS receiving RT. For patients with non-malignant tumors of CNS receiving RT, female, married status, Hispanic ethnicity, surgery, and tumor site (brain exclude nerve and endocrine, nervous system) were associated with lower risks of cardiac-specific death, while earlier year of diagnosis, older age of diagnosis, Black, larger tumor and bilateral tumor were risk factors for cardiac-specific death.

Conclusions

Our study shows the influencing factors for cardiac-specific death in patients with non-malignant tumors of CNS, and found RT is associated with lower risk of cardiac-specific death. These results can facilitate the identification of patients with non-malignant tumors of CNS who can benefit from RT while avoiding cardiovascular events. In addition, this study helps to enhance the clinical use of RT in these populations, especially in patients who may have impaired cardiac function due to CNS tumors.
Early and mid-term outcome of patients with low-flow–low-gradient aortic stenosis treated with newer-generation transcatheter aortic valves
Authors: Fraccaro Chiara , Tarantini Giuseppe , Rosato Stefano , Baglio Giovanni , Biancari Fausto , Barbanti Marco , Tamburino Corrado , Bedogni Francesco , Ranucci Marco , Ussia Gian Paolo , Seccareccia Fulvia , D'Errigo Paola
Published: October 2022

Patients with non-paradoxical low-flow–low-gradient (LFLG) aortic stenosis (AS) are at increased surgical risk, and thus, they may particularly benefit from transcatheter aortic valve replacement (TAVR). However, data on this issue are still limited and based on the results with older-generation transcatheter heart valves (THVs). The aim of this study was to investigate early and mid-term outcome of TAVR with newer-generation THVs in the setting of LFLG AS. Data for the present analysis were gathered from the OBSERVANT II dataset, a national Italian observational, prospective, multicenter cohort study that enrolled 2,989 consecutive AS patients who underwent TAVR at 30 Italian centers between December 2016 and September 2018, using newer-generation THVs. Overall, 420 patients with LVEF ≤50% and mean aortic gradient <40 mmHg were included in this analysis. The primary outcomes were 1-year all-cause mortality and a combined endpoint including all-cause mortality and hospital readmission due to congestive heart failure (CHF) at 1 year. A risk-adjusted analysis was performed to compare the outcome of LFLG AS patients treated with TAVR (n = 389) with those who underwent surgical aortic valve replacement (SAVR, n = 401) from the OBSERVANT I study. Patients with LFLG AS undergoing TAVR were old (mean age, 80.8 ± 6.7 years) and with increased operative risk (mean EuroSCORE II, 11.5 ± 10.2%). VARC-3 device success was 83.3% with 7.6% of moderate/severe paravalvular leak. Thirty-day mortality was 3.1%. One-year all-cause mortality was 17.4%, and the composite endpoint was 34.8%. Chronic obstructive pulmonary disease (HR 1.78) and EuroSCORE II (HR 1.02) were independent predictors of 1-year mortality, while diabetes (HR 1.53) and class NYHA IV (HR 2.38) were independent predictors of 1-year mortality or CHF. Compared with LFLG AS treated with SAVR, TAVR patients had a higher rate of major vascular complications and permanent pacemaker, while SAVR patients underwent more frequently to blood transfusion, cardiogenic shock, AKI, and MI. However, 30-day and 1-year outcomes were similar between groups. Patients with non-paradoxical LFLG AS treated by TAVR were older and with higher surgical risk compared with SAVR patients. Notwithstanding, TAVR was safe and effective with a similar outcome to SAVR at both early and mid-term.
University teachers' self-perception of digital research competencies. A qualitative study conducted in Peru
Authors: Suyo-Vega Josefina Amanda , Meneses-La-Riva Monica Elisa , Fernández-Bedoya Víctor Hugo , Ocupa-Cabrera Hitler Giovanni , Alvarado-Suyo Sofía Almendra , da Costa Polonia Ana , Miotto Angélica Inês , Gago-Chávez Johanna de Jesús Stephanie
Published: October 2022

Previous research warns about the limitations that some university teachers in Ibero-America have in relation to digital research competencies. The objective of this research was to analyze the research competencies from the university teacher's self-perception, contrasted with the classroom evaluation. The study had a qualitative approach. Interviews were conducted via the Zoom virtual platform, and recordings (of an average of 4 h each) of classes delivered by 10 teachers with an average age of 58 years old, in charge of scientific research courses at the postgraduate level in Peruvian universities were analyzed. The instruments used included an in-depth interview guide and a checklist. The results show that university teachers perceive themselves as specialists in the area of research, however, they present limitations when transmitting knowledge during the teaching-learning process. There is evidence of a lack of pedagogy, as well as limitations in the use of digital resources and technological tools due to their resistance to change. The conclusions reveal that it is key to make teachers aware of the paradigm shift, with a teaching that includes as digital competencies: knowing how to create and manipulate data, knowing how to use programs and information systems, knowing how to socialize and collaborate in digital environments, knowing how to exercise and respect a digital citizenship, knowing how to manage knowledge assertively, and, as we propose in this paper, knowing how to be a researcher in a digital environment.
Accessibility service providers’ perceptions of college students with autism spectrum disorder
Authors: Gelbar Nicholas , Cascio Alexandra , Madaus Joseph , Reis Sally
Published: October 2022

Increasing numbers of individuals with Autism Spectrum Disorder (ASD) are pursuing postsecondary education opportunities, including college degree programs. Many receive supports and accommodations from their college accessibility service office. In this study, results of an online survey completed by 147 college accessibility services personnel summarized their perceptions of the facilitators and barriers faced by college students with ASD. Descriptive statistics and qualitative coding procedures were utilized to analyze the data. The participants indicated that the academic preparation of college students with ASD varies. Respondents believed that the most important facilitators of success were the presence of appropriate executive function, social, and self-determination/self-advocacy skills in students, and the absence of these skills was reported as a major barrier to the success of college students with ASD. Respondents also believed that the students’ ability to self-advocate, make independent decisions, self-regulate behaviors, and use appropriate coping and study strategies facilitate the success of college students with ASD. Implications of these findings and suggested directions for future research are offered.
The potential impacts of circadian rhythm disturbances on male fertility
Authors: Li Tao , Bai Yunjin , Jiang Yiting , Jiang Kehua , Tian Ye , Gu Jiang , Sun Fa
Published: October 2022

A circadian rhythm is an internalized timing system that synchronizes the cellular, behavioral, and physiological processes of organisms to the Earth’s rotation. Because all physiological activities occur at a specific time, circadian rhythm disturbances can lead to various pathological disorders and diseases. Growing evidence has shown that the circadian clock is tightly connected to male fertility, and circadian perturbations contribute to infertility. The night shiftwork, insufficient sleep, and poor sleep quality are common causes of circadian disturbances, and many studies have reported that they impair sperm quality and increase the risk of male infertility. However, research on the impacts of light, body temperature, and circadian/circannual rhythms is relatively lacking, although some correlations have been demonstrated. Moreover, as the index of sperm quality was diverse and study designs were non-uniform, the conclusions were temporarily inconsistent and underlying mechanisms remain unclear. A better understanding of whether and how circadian disturbances regulate male fertility will be meaningful, as more scientific work schedules and rational lifestyles might help improve infertility.
Five immune-related genes as diagnostic markers for endometriosis and their correlation with immune infiltration
Authors: Huang Yi , Li Qiong , Hu Rui , Li Ruiyun , Yang Yuan
Published: October 2022

Endometriosis (EMS) is a chronic disease that can cause dysmenorrhea, chronic pelvic pain, and infertility, among other symptoms. EMS diagnosis is often delayed compared to other chronic diseases, and there are currently no accurate, easily accessible, and non-invasive diagnostic tools. Therefore, it is important to elucidate the mechanism of EMS and explore potential biomarkers and diagnostic tools for its accurate diagnosis and treatment. In the present study, we comprehensively analyzed the differential expression, immune infiltration, and interactions of EMS-related genes in three Homo sapiens datasets. Our results identified 332 differentially expressed genes (DEGs) associated with EMS. Gene ontology analysis showed that these changes mainly focused on the positive regulation of endometrial cell proliferation, cell metabolism, and extracellular space, and EMS involved the integrin, complement activation, folic acid metabolism, interleukin, and lipid signaling pathways. The LASSO regression model was established using immune DEGs with an area under the curve of 0.783 for the internal dataset and 0.656 for the external dataset. Five genes with diagnostic value, ACKR1, LMNB1, MFAP4, NMU, and SEMA3C, were screened from M1 and M2 macrophages, activated mast cells, neutrophils, natural killer cells, follicular T helper cells, CD8+, and CD4+ cells. A protein−protein interaction network based on the immune DEGs was constructed, and ten hub genes with the highest scores were identified. Our results may provide a framework for the development of pathological molecular networks in EMS.
Leptin and environmental temperature as determinants of bone marrow adiposity in female mice
Authors: Turner Russell T. , Nesser Kira L. , Philbrick Kenneth A. , Wong Carmen P. , Olson Dawn A. , Branscum Adam J. , Iwaniec Urszula T.
Published: October 2022

Bone marrow adipose tissue (BMAT) levels are higher in distal femur metaphysis of female mice housed at thermoneutral (32°C) than in mice housed at 22°C, as are abdominal white adipose tissue (WAT) mass, and serum leptin levels. We performed two experiments to explore the role of increased leptin in temperature-enhanced accrual of BMAT. First, we supplemented 6-week-old female C57BL/6J (B6) mice with leptin for 2 weeks at 10 µg/d using a subcutaneously implanted osmotic pump. Controls consisted of ad libitum (ad lib) fed mice and mice pair fed to match food intake of leptin-supplemented mice. The mice were maintained at 32°C for the duration of treatment. At necropsy, serum leptin in leptin-supplemented mice did not differ from ad lib mice, suggesting suppression of endogenous leptin production. In support, Ucp1 expression in BAT, percent body fat, and abdominal WAT mass were lower in leptin-supplemented mice. Leptin-supplemented mice also had lower BMAT and higher bone formation in distal femur metaphysis compared to the ad lib group, changes not replicated by pair-feeding. In the second experiment, BMAT response was evaluated in 6-week-old female B6 wild type (WT), leptin-deficient ob/ob and leptin-treated (0.3 μg/d) ob/ob mice housed at 32°C for the 2-week duration of the treatment. Compared to mice sacrificed at baseline (22°C), BMAT increased in ob/ob mice as well as WT mice, indicating a leptin independent response to increased temperature. However, infusion of ob/ob mice with leptin, at a dose rate having negligible effects on either energy metabolism or serum leptin levels, attenuated the increase in BMAT. In summary, increased housing temperature and increased leptin have independent but opposing effects on BMAT in mice.
Tortuosity of branch retinal artery is more associated with the genesis and progress of diabetic retinopathy
Authors: Song Yunfeng , Zhou Zheng , Liu Henan , Du Runyu , Zhou Yaoyao , Zhu Shanshan , Chen Shuo
Published: October 2022

Objective

The purpose of this study is to investigate the potential of using the tortuosity of branch retinal artery as a more promising indicator for early detection and accurate assessment of diabetic retinopathy (DR).

Design and method

The diagnoses, consisting of whether DR or not as well as DR severity, were given by ophthalmologists upon the assessment of those fundus images from 495 diabetic patients. Meanwhile, benefiting from those good contrast and high optical resolution fundus images taken by confocal scanning laser ophthalmoscope, the branch arteries, branch veins, main arteries and main veins in retina can be segmented independently, and the tortuosity values of them were further extracted to investigate their potential correlations with DR genesis and progress based on one-way ANOVA test.

Results

For both two comparisons, i.e., between non-DR group and DR group as well as among groups with different DR severity levels, larger tortuosity increments were always observed in retinal arteries and the increments in branch retinal vessels were even larger. Furthermore, it was newly found that branch arterial tortuosity was significantly associated with both DR genesis (p=0.030) and DR progress (p<0.001).

Conclusion

Based on this cohort study of 495 diabetic patients without DR and with different DR severity, the branch arterial tortuosity has been found to be more closely associated with DR genesis as well as DR progress. Therefore, the branch arterial tortuosity is expected to be a more direct and specific indicator for early detection of DR as well as accurate assessment of DR severity, which can further guide timely and rational management of DR to prevent from visual impairment or even blindness resulting from DR.
Association between liver-type fatty acid-binding protein and hyperuricemia before and after laparoscopic sleeve gastrectomy
Authors: You Hui , Ma Huihui , Wang Xingchun , Wen Xin , Zhu Cuiling , Mao Wangjia , Bu Le , Zhang Manna , Yin Jiajing , Du Lei , Cheng Xiaoyun , Chen Haibing , Zhang Jun , Qu Shen
Published: October 2022

Background

Liver-type fatty acid-binding protein (FABP1) contributes to metabolic disorders. However, the relationship between FABP1 and hyperuricemia remains unknown. We aimed to evaluate the correlation between serum FABP1 and hyperuricemia in patients with obesity before and after laparoscopic sleeve gastrectomy (LSG).

Methods

We enrolled 105 patients (47 men and 58 women) with obesity who underwent LSG. They were divided into two groups: normal levels of uric acid (UA) (NUA, n = 44) and high levels of UA (HUA, n = 61) with matching sexes. FABP1 levels and other biochemical parameters were measured at baseline and 3, 6, and 12 months after LSG.

Results

Serum FABP1 levels were significantly higher in the HUA group than in the NUA group (34.76 ± 22.69 ng/mL vs. 25.21 ± 21.68 ng/mL, P=0.024). FABP1 was positively correlated with UA (r=0.390, P=0.002) in the HUA group. The correlation still existed after adjusting for confounding factors. Preoperative FABP1 levels were risk factors for hyperuricemia at baseline. UA and FABP1 levels decreased at 3, 6, and 12 months postoperatively. FABP1 showed a more significant decrease in the HUA group than in the NUA group at 12 months (27.06 ± 10.98 ng/mL vs. 9.54 ± 6.52 ng/mL, P=0.003). Additionally, the change in FABP1 levels positively correlated with changes in UA levels in the HUA group 12 months postoperatively (r=0.512, P=0.011).

Conclusions

FABP1 was positively associated with UA and may be a risk factor for hyperuricemia in obesity. FABP1 levels were higher but decreased more after LSG in obese patients with hyperuricemia than in those without hyperuricemia.
Proton-conducting ceramics for water electrolysis and hydrogen production at elevated pressure
Authors: Herradon C. , Le L. , Meisel C. , Huang J. , Chmura C. , Kim Y.D. , Cadigan C. , O’Hayre R. , Sullivan N.P.
Published: October 2022

Pressurized operation is advantageous for many electrolysis and electrosynthesis technologies. The effects of pressure have been studied extensively in conventional oxygen-ion conducting solid-oxide electrochemical cells. In constrast, very few studies have examined pressurized operation in proton-conducting electroceramics. Protonic ceramics offer high proton conductivity at intermediate temperatures (∼400–600°C) that are well-matched to many important thermochemical synthesis processes. Pressurized operation can bring significant additional benefits and/or provide access to synthetic pathways otherwise unavailable or thermodynamically disfavorable under ambient conditions and in higher- or lower-temperature electrochemical devices. Here we examine pressurized steam electrolysis in protonic-ceramic unit-cell stacks based on a BaCe0.4Zr0.4Y0.1Yb0.1O3−δ (BCZYYb4411) electrolyte, a Ni–BZCYYb4411 composite negatrode (fuel electrode) and a BaCo0.4Fe0.4Zr0.1Y0.1O3−δ (BCFZY) positrode (air-steam electrode). The cells are packaged within unit-cell stacks, including metallic interconnects, current collectors, sealing glasses and gaskets sealed by mechanical compression. The assembly is packaged within a stainless steel vessel for performance characterization at elevated pressure. Protonic-ceramic electrolyzer performance is analyzed at 550°C and pressures up to 12 bara. Increasing the operating pressure from 2.1 to 12.6 bara enables a 40% overall decrease in the over-potential required to drive electrolysis at 500 mA cm−2, with a 33% decrease in the cell ohmic resistance and a 60% decrease in the cell polarization resistance. Faradaic efficiency is also found to increase with operating pressure. These performance improvements are attributed to faster electrode kinetics, improved gas transport, and beneficial changes to the defect equilibria in the protonic-ceramic electrolyte, which more than compensate for the slight increase in Nernst potential brought by pressurized operation. Electrochemical impedance spectroscopy (EIS) coupled with distribution of relaxation time (DRT) analysis provides greater insight into the fundamental processes altered by pressurized operation.
Drivers for the artisanal fisheries production in the Magdalena River
Authors: Jiménez-Segura Luz , Restrepo-Ángel Juan D. , Hernandez-Serna Andrés
Published: October 2022

We review knowledge on the Magdalena River in Colombia and its fish to identify those drivers that influence the artisanal fisheries production. We identify eight direct drivers (four natural and four anthropogenic) and at least four indirect drivers. Those drivers modify conditions in the fluvial network that promote fish movements, reproduction, and their larvae survivor. Landscape, rains, floods, connectivity of the fluvial net as land cover change, water pollution, hydropower, and alien species are the natural and anthropogenic direct drivers described in this article. The river–lake interaction dynamics in the Magdalena River are determined by two rainy cycles per year. Two seasonal flooding periods induce two cycles in the biological productivity of floodplains because water and sediment inputs. The most visible consequences in these hydrological cycles are the migrations of potamodromous fish and the periodic increase in the artisanal fishery production. Major floodplains are reducing their storage capacity by trapping ∼10%–40% of upstream sediment production. This process induces many research questions about rates of biomass production, carbon fluxes in the basin, impacts of human-induced erosion, and increasing rates of sediment load on floodplain connectivity, but still there is not enough data to answer them. Finally, we make some suggestions toward the sustainability of the Magdalena floodplains. The well-being of the floodplain ecosystems and their connectivity with the main river are the main tools to preserve and manage the ecosystem services of the Magdalena River and its floodplains lakes.
Has China’s coal consumption really peaked?—Prediction and scenario analysis of China’s coal consumption peak under the double-carbon target
Authors: Wang Wensheng , Kao Xiaoxuan , Lin Zhihan , Zhang Yue
Published: October 2022

After China’s “Double Carbon” strategy was proposed to reduce energy and consumption, the optimization of China’s energy consumption structure and whether China’s coal consumption have already reached its peak once again attracted attention. This paper uses the theory of system dynamics to build a system dynamics model of coal consumption. Based on data analysis and the grey prediction model, three categories and nine sub-scenarios are established and the peak coal consumption is analyzed under each scenario. The results show that: The peak of coal consumption in China can echo the strategic goal of peaking carbon in 2030, which is in line with the laws of reality. The economic growth rate has the greatest influence on the coal consumption peak, followed by industrial structure and coal consumption intensity, and the population growth rate has the least influence. The SD3 scenario is the optimal path for China’s future coal consumption development. Under this scenario, coal consumption will peak at 437.8 million tons in 2027. If the future energy consumption trend is close to the SD3 scenario, the socioeconomic growth rate will slow down, the population growth rate will slow down, the industrial structure optimization degree will be higher, and the intensity of coal consumption will be lower. The coal consumption peak varies greatly according to different development goals and transformation dynamics. Under the constraints of the established peak time, the scenario of coal consumption peak has a variety of combinations.
Differential sensitivity of offspring from four species of goodeine freshwater fish to acute exposure to nitrates
Authors: Villa-Villaseñor Ivette Marai , Yáñez-Rivera Beatriz , Rueda-Jasso Rebeca Aneli , Herrera-Vargas Ma. Antonia , Hernández-Morales Rubén , Meléndez-Herrera Esperanza , Domínguez-Domínguez Omar
Published: October 2022

Nitrate-nitrogen (NO3-N) pollution related to anthropogenic activities is increasing in freshwater ecosystems. Knowledge about NO3-N sensitivity in freshwater wild fish is needed to understand the differential tolerance between species. Goodeinae is a subfamily of 41 endemic fishes that inhabit central Mexico, with 33 species in the IUCN red list and three extinct. Distributional patterns suggest tolerant and sensitive goodeines related to the conservation gradient of freshwater ecosystems. Four species with a differential distribution and tolerance were selected to evaluate their physiological responses to NO3-N. Fish were exposed to different NO3-N concentrations for 96 h and the median lethal concentration (LC50) was determined. Swimming disorders plus gill and liver histopathological indexes were estimated and incorporated into an Integrated Biomarker Response (IBR) for each species. Skiffia lermae (LC50 = 474.332 mg/L) and Xenotoca variata (LC50 = 520.273 mg/L) were more sensitive than Goodea atripinnis (LC50 = 953.049 mg/L) and Alloophorus robustus (LC50 = 1537.13 mg/L). The typical histological damage produced by NaNO3-N exposure was fusion of secondary lamellae in gills. This was present in all species and cellular degeneration was observed at the highest concentrations. Secondary lamellae aneurysms were only observed in G. atripinnis. Liver alterations included vascular dilation in hepatic sinusoids, hyperemia and nuclear hypertrophy; higher concentrations produced hepatocyte cytoplasmic vacuolation and reduced frequency of cell nuclei. Behavioral and histopathological alterations could explain the differential species sensitivity. The results suggest that species which preserve gill function and transfer the task of detoxification to the liver might have the best chance of surviving in polluted environments. Moreover, species previously considered as tolerant may be highly susceptible to NaNO3-N exposure. Therefore, it is necessary to closely monitor NaNO3-N concentrations in freshwater ecosystems and, if possible, reduce their levels to avoid the loss of wild populations.
Experimental test of the contributions of initial variation and new mutations to adaptive evolution in a novel environment
Authors: Izutsu Minako , Lenski Richard E.
Published: October 2022

Experimental evolution is an approach that allows researchers to study organisms as they evolve in controlled environments. Despite the growing popularity of this approach, there are conceptual gaps among projects that use different experimental designs. One such gap concerns the contributions to adaptation of genetic variation present at the start of an experiment and that of new mutations that arise during an experiment. The primary source of genetic variation has historically depended largely on the study organisms. In the long-term evolution experiment (LTEE) usingEscherichia coli, for example, each population started from a single haploid cell, and therefore, adaptation depended entirely on new mutations. Most other microbial evolution experiments have followed the same strategy. By contrast, evolution experiments using multicellular, sexually reproducing organisms typically start with preexisting variation that fuels the response to selection. New mutations may also come into play in later generations of these experiments, but it is generally difficult to quantify their contribution in these studies. Here, we performed an experiment usingE. colito compare the contributions of initial genetic variation and new mutations to adaptation in a new environment. Our experiment had four treatments that varied in their starting diversity, with 18 populations in each treatment. One treatment depended entirely on new mutations, while the other three began with mixtures of clones, whole-population samples, or mixtures of whole-population samples from the LTEE. We tracked a genetic marker associated with different founders in two treatments. These data revealed significant variation in fitness among the founders, and that variation impacted evolution in the early generations of our experiment. However, there were no differences in fitness among the treatments after 500 or 2,000 generations in the new environment, despite the variation in fitness among the founders. These results indicate that new mutations quickly dominated, and eventually they contributed more to adaptation than did the initial variation. Our study thus shows that preexisting genetic variation can have a strong impact on early evolution in a new environment, but new beneficial mutations may contribute more to later evolution and can even drive some initially beneficial variants to extinction.
Dominant Dendrobium officinale mycorrhizal partners vary among habitats and strongly induce seed germination in vitro
Authors: Zhang Liyue , Rammitsu Kento , Tetsuka Kenshi , Yukawa Tomohisa , Ogura-Tsujita Yuki
Published: October 2022

Dendrobium officinale(Orchidaceae) is an endangered epiphytic orchid that has been well studied as a medicinal plant. Although previous studies have shown that various fungal isolates promoteD. officinaleseed germination and seedling developmentin vitro, mycorrhizal associations among its wild populations remain poorly understood. In this study, we identified mycorrhizal fungi associated withD.officinale(36 individuals from six sites) using Sanger sequencing and compared fungal communities among sites and habitats (lithophytic vs. epiphytic individuals). Among the obtained sequences, 76 belonged to orchid mycorrhizal fungi (OMF), among which Tulasnellaceae accounted for 45.8% and Serendipitaceae for 28.1%. The Serendipitaceae operational taxonomic unit (OTU) SE1 was the most dominant partner, accounting for 27.1% of all detected fungal sequences, followed by a Tulasnellaceae OTU, TU27, which accounted for 15.6%. The relative frequencies of Serendipitaceae and Tulasnellaceae differed greatly between lithophytic and epiphytic individuals. Serendipitaceae accounted for 47.3% of the OMF sequences among lithophytes, and Tulasnellaceae for 95.2% among epiphytes. Mycorrhizal community composition also varied among sites. We further conductedin vitrosymbiotic culture from seeds with six fungal isolates. Two Serendipitaceae and two Tulasnellaceae isolates, including SE1 and TU27, significantly promoted seed germination and seedling development. These results indicate thatD.officinaleis mainly associated with Tulasnellaceae and Serendipitaceae as its main fungal partners, which strongly induced seed germination and seedling developmentin vitro, suggesting their association withD.officinalethrough its life cycle.
Pathogenic mitochondrial DNA 3243A>G mutation: From genetics to phenotype
Authors: Li Danyang , Liang Chunmei , Zhang Tao , Marley Jordan Lee , Zou Weiwei , Lian Muqing , Ji Dongmei
Published: October 2022

The mitochondrial DNA (mtDNA) m.3243A>G mutation is one of the most common pathogenic mtDNA variants, showing complex genetics, pathogenic molecular mechanisms, and phenotypes. In recent years, the prevention of mtDNA-related diseases has trended toward precision medicine strategies, such as preimplantation genetic diagnosis (PGD) and mitochondrial replacement therapy (MRT). These techniques are set to allow the birth of healthy children, but clinical implementation relies on thorough insights into mtDNA genetics. The genotype and phenotype of m.3243A>G vary greatly from mother to offspring, which compromises genetic counseling for the disease. This review is the first to systematically elaborate on the characteristics of the m.3243A>G mutation, from genetics to phenotype and the relationship between them, as well as the related influencing factors and potential strategies for preventing disease. These perceptions will provide clarity for clinicians providing genetic counseling to m.3243A>G patients.
Genome-wide association study reveals the genetic basis of brace root angle and diameter in maize
Authors: Sun Daqiu , Chen Sibo , Cui Zhenhai , Lin Jingwei , Liu Meiling , Jin Yueting , Zhang Ao , Gao Yuan , Cao Huiying , Ruan Yanye
Published: October 2022

Brace roots are the main organ to support the above-ground part of maize plant. It involves in plant growth and development by water absorption and lodging resistance. The bracing root angle (BRA) and diameter (BRD) are important components of brace root traits. Illuminating the genetic basis of BRA and BRD will contribute the improvement for mechanized harvest and increasing production. A GWAS of BRA and BRD was conducted using an associated panel composed of 508 inbred lines of maize. The broad-sense heritability of BRA and BRD was estimated to be respectively 71% ± 0.19 and 52% ± 0.14. The phenotypic variation of BRA and BRD in the non-stiff stalk subgroup (NSS) and the stiff stalk subgroup (SS) subgroups are significantly higher than that in the tropical/subtropical subgroup (TST) subgroups. In addition, BRA and BRD are significantly positive with plant height (PH), ear length (EL), and kernel number per row (KNPR). GWAS revealed 27 candidate genes within the threshold of p < 1.84 × 10−6 by both MLM and BLINK models. Among them, three genes, GRMZM2G174736, GRMZM2G445169 and GRMZM2G479243 were involved in cell wall function, and GRMZM2G038073 encoded the NAC transcription factor family proteins. These results provide theoretical support for clarifying the genetic basis of brace roots traits.
Identification of genetic variants in five chinese families with keratoconus: Pathogenicity analysis and characteristics of parental corneal topography
Authors: Cheng Wan-Yu , Yang Shang-Ying , Huang Xiao-Yu , Zi Fei-Yin , Li Hui-Ping , Sheng Xun-Lun
Published: October 2022

Purpose: The study aims to identify genetic variants in five Chinese families with Keratoconus (KC) and describe the characteristics of parental corneal topography.

Methods: Fifteen participants, including five probands and ten parents from five Chinese families with KC, were recruited for genetic and clinical analyses. Targeted next-generation sequencing using a custom-designed panel for KC was applied on the probands for variant identification. Sanger sequencing and cosegregation analysis of the suspected pathogenic variants were performed on the family members. The pathogenicities of variants were evaluated according to the American College of Medical Genetics and Genomics guidelines (ACMG). Pentacam 3D anterior segment analysis system was applied for keratectasia detection and the Corvis ST for corneal biomechanics measurement. Fifteen parameters were recorded, including nine keratectasia indicators (BAD-D, TP, Kmax, Df, Db, Dp, Dt, Da, ARTH), six corneal biomechanical indicators (CBI, DA ratio, SP-A1, IR, bIOP, TBI).

Results: A total of six novel variants, including five missense variants and one frameshift variant, were detected in the HMX1, SLC4A11, TGFBI, PIKFYVE, and ZEB1 genes in five probands, all of which showed co-segregation of genotype and clinical phenotype and were determined to be pathogenic. The genetic model was autosomal dominant (AD) in four families and autosomal recessive (AR) in 1 family. The analysis of keratectasia and corneal biomechanical indicators of the proband’s parents (first-generation relatives) in AD families revealed that there were several abnormal indexes in BAD-D, TP, Kmax, Df, Db, Dp, Dt, Da, CBI, DA ratio, SP-A1, IR, bIOP and TBI test indexes, showing clinical characteristics of incipient KC.

Conclusion: Our study shows that variants in HMX1, SLC4A11, TGFBI, PIKFYVE, and ZEB1 were associated with KC. Our study extends the gene spectrum associated with KC, provides novel insights into KC phenotypic assessments, and contributes to early diagnosis for these patients.
Role of epigallocatechin-3- gallate in the regulation of known and novel microRNAs in breast carcinoma cells
Authors: Banerjee Shrila , Mandal Abul Kalam Azad
Published: October 2022

Breast cancer comprises 30% of all cancer cases among the world’s women population. MicroRNAs are small, endogenous, non-coding RNAs that regulate cell proliferating and apoptotic pathways by modulating expressions of related genes. Phytochemicals like epigallocatechin-3-gallate (EGCG) are known to have a chemotherapeutic effect on cancer often through the regulation of microRNAs. The aim is to find out the key known and novel miRNAs, which are controlled by EGCG in breast cancer cell line MDA-MB-231. Next-generation sequencing (NGS) revealed 1,258 known and 330 novel miRNAs from untreated and 83 μM EGCG (IC50 value of EGCG) treated cells. EGCG modulated 873 known and 47 novel miRNAs in the control vs. treated sample. The hypothesis of EGCG being a great modulator of miRNAs that significantly control important cancer-causing pathways has been established by analyzing with Kyoto Encyclopedia of Genes and Genomes (KEGG) and Protein Analysis Through Evolutionary Relationships (PANTHER) database. Validation of known and novel miRNA expression differences in untreated vs. treated cells was done using qPCR. From this study, a few notable miRNAs were distinguished that can be used as diagnostics as well as prognostic markers for breast cancer.
Monocyte-derived peritoneal macrophages protect C57BL/6 mice against surgery-induced adhesions
Authors: Sahputra Rinal , Dejyong Krittee , Woolf Adrian S. , Mack Matthias , Allen Judith E. , Rückerl Dominik , Herrick Sarah E.
Published: October 2022

Peritoneal adhesions commonly occur after abdominal or pelvic surgery. These scars join internal organs to each other or to the cavity wall and can present with abdominal or pelvic pain, and bowel obstruction or female infertility. The mechanisms underlying adhesion formation remain unclear and thus, effective treatments are not forthcoming. Peritoneal macrophages accumulate after surgery and previous studies have attributed either pro- or anti-scarring properties to these cells. We propose that there are complex and nuanced responses after surgery with respect to both resident and also monocyte-derived peritoneal macrophage subpopulations. Moreover, we contend that differences in responses of specific macrophage subpopulations in part explain the risk of developing peritoneal scars. We characterized alterations in peritoneal macrophage subpopulations after surgery-induced injury using two strains of mice, BALB/c and C57BL/6, with known differences in macrophage response post-infection. At 14 days post-surgery, BALB/c mice displayed more adhesions compared with C57BL/6 mice. This increase in scarring correlated with a lower influx of monocyte-derived macrophages at day 3 post-surgery. Moreover, BALB/c mice showed distinct macrophage repopulation dynamics after surgery. To confirm a role for monocyte-derived macrophages, we used Ccr2-deficient mice as well as antibody-mediated depletion of CCR2 expressing cells during initial stages of adhesion formation. Both Ccr2-deficient and CCR2-depleted mice showed a significant increase in adhesion formation associated with the loss of peritoneal monocyte influx. These findings revealed an important protective role for monocyte-derived cells in reducing adhesion formation after surgery.
Case Report: Para-infectious cranial nerve palsy after bacterial meningitis
Authors: Zanotelli Giovanni , Bresciani Lorenzo , Anglani Mariagiulia , Miscioscia Alessandro , Rinaldi Francesca , Puthenparampil Marco
Published: October 2022

A 27-year-old woman was admitted to our hospital for fever, associated with headache, nausea, and vomiting, and she rapidly developed mild left facial nerve palsy and diplopia. Neurological examination revealed mild meningitis associated with bilateral VI cranial nerve palsy and mild left facial palsy. As central nervous system (CNS) infection was suspected, a diagnostic lumbar puncture was performed, which revealed 1,677 cells/μl, 70% of which were polymorphonuclear leukocytes. Moreover, multiplex PCR immunoassay was positive for Neisseria meningitidis, supporting the diagnosis of bacterial meningitis. Finally, IgG oligoclonal bands (IgGOB) were absent in serum and cerebrospinal fluid (CSF). Therefore, ceftriaxone antibiotic therapy was started, and in the following days, the patient’s signs and symptoms improved, with complete remission of diplopia and meningeal signs within a week. On the contrary, left facial nerve palsy progressively worsened into a severe bilateral deficit. A second lumbar puncture was therefore performed: the CSF analysis revealed a remarkable decrease of pleocytosis with a qualitative modification (only lymphocytes), and oligoclonal IgG bands were present. A new brain MRI was performed, showing a bilateral gadolinium enhancement of the intrameatal VII and VIII cranial nerves bilaterally. Due to suspicion of para-infectious etiology, the patient was treated with oral steroid (prednisolone 1 mg/kg/day), with a progressive and complete regression of the symptoms. We suggest that in this case, after a pathogen-driven immunological response (characterized by relevant CSF mixed pleocytosis and no evidence of IgGOB), a para-infectious adaptive immunity-driven reaction (with mild lymphocyte pleocytosis and pattern III IgGOB) against VII and VIII cranial nerves started. Indeed, steroid administration caused a rapid and complete restoration of cranial nerve function.
Longitudinal cellular and humoral immune responses after triple BNT162b2 and fourth full-dose mRNA-1273 vaccination in haemodialysis patients
Authors: Becker Matthias , Cossmann Anne , Lürken Karsten , Junker Daniel , Gruber Jens , Juengling Jennifer , Ramos Gema Morillas , Beigel Andrea , Wrenger Eike , Lonnemann Gerhard , Stankov Metodi V. , Dopfer-Jablonka Alexandra , Kaiser Philipp D. , Traenkle Bjoern , Rothbauer Ulrich , Krause Gérard , Schneiderhan-Marra Nicole , Strengert Monika , Dulovic Alex , Behrens Georg M. N.
Published: October 2022

Haemodialysis patients respond poorly to vaccination and continue to be at-risk for severe COVID-19. Therefore, dialysis patients were among the first for which a fourth COVID-19 vaccination was recommended. However, targeted information on how to best maintain immune protection after SARS-CoV-2 vaccinations in at-risk groups for severe COVID-19 remains limited. We provide, to the best of our knowledge, for the first time longitudinal vaccination response data in dialysis patients and controls after a triple BNT162b2 vaccination and in the latter after a subsequent fourth full-dose of mRNA-1273. We analysed systemic and mucosal humoral IgG responses against the receptor-binding domain (RBD) and ACE2-binding inhibition towards variants of concern including Omicron and Delta with multiplex-based immunoassays. In addition, we assessed Spike S1-specific T-cell responses by interferon γ release assay. After triple BNT162b2 vaccination, anti-RBD B.1 IgG and ACE2 binding inhibition reached peak levels in dialysis patients, but remained inferior compared to controls. Whilst we detected B.1-specific ACE2 binding inhibition in 84% of dialysis patients after three BNT162b2 doses, binding inhibition towards the Omicron variant was only detectable in 38% of samples and declining to 16% before the fourth vaccination. By using mRNA-1273 as fourth dose, humoral immunity against all SARS-CoV-2 variants tested was strongly augmented with 80% of dialysis patients having Omicron-specific ACE2 binding inhibition. Modest declines in T-cell responses in dialysis patients and controls after the second vaccination were restored by the third BNT162b2 dose and significantly increased by the fourth vaccination. Our data support current advice for a four-dose COVID-19 immunisation scheme for at-risk individuals such as haemodialysis patients. We conclude that administration of a fourth full-dose of mRNA-1273 as part of a mixed mRNA vaccination scheme to boost immunity and to prevent severe COVID-19 could also be beneficial in other immune impaired individuals. Additionally, strategic application of such mixed vaccine regimens may be an immediate response against SARS-CoV-2 variants with increased immune evasion potential.