bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations between statins and adverse events in secondary prevention of cardiovascular disease: Pairwise, network, and dose-response meta-analyses of 47 randomized controlled trials
Authors: Wang Xinyi , Li Jingen , Wang Tongxin , Zhang Zihao , Li Qiuyi , Ma Dan , Chen Zhuo , Ju Jianqing , Xu Hao , Chen Keji
Published: August 2022

Objectives

To explore the associations between different types and doses of statins and adverse events in secondary prevention of cardiovascular disease.

Methods

We searched PubMed, Embase, and Cochrane databases for randomized controlled trials that compared statins with non-statin controls or different types or doses of statins. The primary outcomes included muscle condition, transaminase elevations, renal insufficiency, gastrointestinal discomfort, cancer, new onset or exacerbation of diabetes, cognitive impairment, and eye condition. We also analyzed myocardial infarction (MI), stroke, death from cardiovascular diseases (CVD), and all-cause death as the secondary outcomes to compare the potential harms with the benefits of statins. We conducted pairwise meta-analyses to calculate the odds ratio (OR) and 95% confidence intervals (CIs) for each outcome. Network meta-analyses were performed to compare the adverse effects of different statins. An Emax model was used to examine the dose-response relationships of the adverse effects of each statin.

Results

Forty-seven trials involving 107,752 participants were enrolled and followed up for 4.05 years. Compared with non-statin control, statins were associated with an increased risk of transaminase elevations [OR 1.62 (95% CI 1.20 to 2.18)]. Statins decreased the risk of MI [OR 0.66 (95% CI 0.61 to 0.71), P < 0.001], stroke [OR 0.78 (95% CI 0.72 to 0.84), P < 0.001], death from CVD [OR 0.77 (95% CI 0.72 to 0.83), P < 0.001] and all-cause death [OR 0.83 (95% CI 0.79 to 0.88), P < 0.001]. Atorvastatin showed a higher risk of transaminase elevations than non-statin control [OR 4.0 (95% CI 2.2 to 7.6)], pravastatin [OR 3.49 (95% CI 1.77 to 6.92)] and simvastatin [OR 2.77 (95% CI 1.31 to 5.09)], respectively. Compared with atorvastatin, simvastatin was associated with a lower risk of muscle problems [OR 0.70 (95% CI 0.55 to 0.90)], while rosuvastatin showed a higher risk [OR 1.75 (95% CI 1.17 to 2.61)]. An Emax dose-response relationship was identified for the effect of atorvastatin on transaminase elevations.

Conclusion

Statins were associated with increased risks of transaminases elevations in secondary prevention. Our study provides the ranking probabilities of statins that can help clinicians make optimal decisions when there is not enough literature to refer to.

Systematic review registration

[https://www.crd.york.ac.uk/prospero/], identifier [CRD42021285161].
De-escalation of antiplatelet therapy in acute coronary syndromes: Why, how and when?
Authors: Galli Mattia , Angiolillo Dominick J.
Published: August 2022

The synergistic blockade of the key platelet signaling pathways of cyclooxygenase-1 blockade and P2Y12 signaling by combining aspirin plus a potent P2Y12 inhibitor (prasugrel or ticagrelor), the so called dual antiplatelet treatment (DAPT), has represented the antithrombotic regimen of choice in patients with acute coronary syndrome (ACS) for nearly a decade. Nevertheless, the use of such antiplatelet treatment regimen, while reduced the risk of thrombotic complications, it is inevitably associated with increased bleeding and this risk may outweigh the benefit of a reduction of ischemic events in specific subgroup of patients. In light of the adverse prognostic implications of a bleeding complication, there has been a great interest in the development of antiplatelet regimens aimed at reducing bleeding without any trade-off in ischemic events. The fact that the ischemic risk is highest in the early phase after an ACS while the risk of bleeding remains relatively stable over time has represented the rationale for the implementation of a more intense antithrombotic regimen early after an ACS, followed by a less intense antithrombotic regimen thereafter. This practice, known as a “de-escalation” strategy, represents one of the more promising approaches for personalization of antithrombotic therapy in ACS. In this review we discuss the rationale, appraise the evidence and provide practical recommendations on the use of a de-escalation strategy of antiplatelet therapy in patients with an ACS.
Displacement/Length Scaling Relationships for Normal Faults; a Review, Critique, and Revised Compilation
Authors: Lathrop B. A. , Jackson C. A-L. , Bell R. E. , Rotevatn A.
Published: August 2022

The relationship between normal fault displacement (D) and length (L) varies due to numerous factors, including fault size, maturity, basin tectonic history, and host rock lithology. Understanding how fault D and L relate is useful, given related scaling laws are often used to help refine interpretations of often incomplete, subsurface datasets, which has implications for hydrocarbon and low-carbon energy applications. Here we provide a review of D/L scaling laws for normal faults, discuss factors that could influence these relationships, including both geological factors and errors in measurement, and provide a critique of previously published D/L databases. We then present our newly assembled database of 4059 normal faults from 66 sources that include explicit information on: 1) fault length and displacement, 2) host rock lithology, 3) host basin tectonic history, and 4) maturity, as well as fault D and L through time when these data are available. We find an overall scaling law of D = 0.3L0.92, which is similar to previously published scaling equations and that varies in response to the aforementioned geological factors. Our data show that small faults (<1 m length) tend to be over-displaced compared to larger faults, active faults tend to be under-displaced compared to inactive faults, and faults with stiffer host rock lithologies, like igneous and carbonate rocks, tend to be under-displaced with respect to faults within softer, more compliant host rocks, like clastic sedimentary rocks. Our dynamic D/L through time data show that faults follow the hybrid fault growth model, i.e., they initially lengthen, during which time they will appear under-displaced, before accumulating displacement. To the best of our knowledge, this is the first comprehensive, integrated, critical study of D/L scaling laws for normal faults and the factors influencing their growth. These revised relationships can now be utilized for predicting fault length or displacement when only one variable is available and provide the basis for general understanding D/L scaling laws in the context of normal fault growth. This underpinning database is open-access and is available for analysis and manipulation by the broader structural geology community.
Engineering properties and microcosmic mechanism of cement stabilized diatomite
Authors: Cui Su Li , Tao Zhi Peng , Zhang Yang , Su Hang , Jia Yang
Published: August 2022

In this study, the engineering properties of remolded diatomite and the effects of cement on the compression characteristic, strength properties and microstructures of cement-stabilized diatomite were investigated. Samples were prepared and stabilized with different cement content ratios, ranging from 0% to 15% by dry mass. Results show that compared with undisturbed diatomite, the compressibility of the remolded diatomite increases while the strength characteristics decrease. With the increase of cement content, the compressibility of cement-stabilized diatomite is significantly reduced and the strength characteristics are improved. Adding cement to diatomite changes the structure of pure diatomite and forms more tiny pores between cement and diatomite, while curing reduces the porosity ratio of samples and enhance the strength of cement-stabilized diatomite, especially for diatomite with higher cement content. The physical-chemical reactions including hydrolysis and hydration between cement and diatomite increase the content of sodium aluminosilicate, calcium aluminosilicate and other minerals in the soil.
Geophysical evidence for submarine methane seepage on the Western slope of Okinawa Trough
Authors: Luo Di , Cai Feng , Li Qing , Yan Guijing , Sun Yunbao , Li Ang , Dong Gang
Published: August 2022

Identifying seafloor methane seepage efficiently has important implications for assessing environmental impact, reducing the uncertainty of top seal integrity, understanding the petroleum system, and mitigating the drilling hazards due to shallow gas influx. Pore water geochemistry analyses suggest that the study area has an extremely high methane seepage flux and active methane anaerobic oxidation processes. However, geochemical data cannot provide details about the internal seepages. The geophysical dataset from the Western slope of Okinawa Trough, including 2D high-resolution seismic, sub-bottom profiles, and bathymetry, gives us a good opportunity to understand the detailed characteristics of methane seepages in this study. Geophysical data have revealed numerous methane seepage-related features such as seismic chimneys, pockmarks, submarine domes, and amplitude anomalies, including bright spots and enhanced reflections. Pockmarks and domes are often associated with seismic chimneys, indicating that fluid migration is important in their formation. The various geophysical expressions may represent different stages of methane seepage. Fluid quickly drains, causing severe sediment deformation and forming pockmarks, whereas domes may indicate the early stages of fluid discharge. Chimneys that do not extend to the seafloor may indicate that the venting is gradual and focused. Flares linked to domes or pockmarks may indicate that the fluid migration is active. Several factors triggered the existence of methane seepages on the Western slope of the Okinawa Trough, including tectonic setting, overpressure and rapid sedimentation.
Field science in the age of online learning: Dynamic instruction of techniques to assess soil physical properties
Authors: Hinckley Eve-Lyn S. , Fendorf Scott
Published: August 2022

Soil physical properties, such as soil texture, color, bulk density, and porosity are important determinants of water flow (e.g., infiltration and drainage), biogeochemical cycling, and plant community composition. In addition, they reflect the environment in which the soil developed, giving insight into climate, mineralogy, and land cover. While many soil assessments require sophisticated laboratory equipment, some can be made simply by a trained individual, requiring only practice and reference materials. For students in environmental fields, it is particularly important and empowering to learn how to make informed soil observations that provide insights from the soil pedon to the landscape and that can be done within the field setting. Drawing on updated pedagogical approaches, including active learning, small group collaboration, and metacognitive exercises, this paper presents a course module for teaching soil texture and color analysis in the field that can be modified for students from secondary through graduate school. The combination of asynchronous, pre-course readings and assessment; synchronous, in-class instruction, hands-on practice, and application activities; and post-class reflection give students the opportunity to build a strong foundation for making soil observations. This course module is suitable for both in-person and remote learning modalities and can be adapted to a number of course topics across environmental disciplines. Ultimately, the goal is to provide students with exciting, hands-on training that inspires them to learn more about soils regardless of the learning platform.
Congenital vaginal obstruction in a female with Cornelia de Lange syndrome: A case report
Authors: Shen Yiding , Zhao Dongyan , Sun Long , Yang Xiuzhen , Yan Xiang
Published: August 2022

Cornelia de Lange syndrome (CdLS) is a rare genetic disease involving multiorgan systems that varies in clinical manifestations. Female genital abnormalities in patients with CdLS are rarely reported, and current guidelines for CdLS contain little information related to female genital abnormalities. We report a case of classic CdLS with an NIPBL gene pathogenic variant in a 4.5-year-old girl who experienced recurrent urinary tract infections (UTIs) with vesical tenesmus. Urogenital physical and imaging examinations revealed external vaginal orifice obstruction and bilateral vesicoureteral reflux (VUR). Vaginal diaphragm-like tissue resection and vaginal orifice plasty were performed on this patient. The symptoms of urination disorders and recurrent UTIs, as well as VUR grading, improved after relieving the vaginal obstruction during the operation. For female CdLS patients, especially those with VUR, it is necessary to check for genital abnormalities and perform timely treatment, which is of great significance in improving urination disorder symptoms, reducing resistance during voiding, decreasing the occurrence of secondary VUR, and controlling recurrent UTIs.
Nomogram for the cumulative live birth in women undergoing the first IVF cycle: Base on 26, 689 patients in China
Authors: Qu Pengfei , Chen Lijuan , Zhao Doudou , Shi Wenhao , Shi Juanzi
Published: August 2022

Objective

Predictive models of the cumulative live birth (CLB) in women undergoing in vitro fertilization (IVF) treatment are limited. The aim of this study was to develop and validate a nomogram for the CLB in women undergoing the first IVF cycle.

Methods

Based on a cross-sectional study in assisted reproduction center of Northwest Women’s and Children’s Hospital, 26,689 Chinese patients who underwent IVF treatment was used to develop and validate a prediction model for the CLB. Among those participants, 70% were randomly assigned to the training set (18,601 patients), while the remaining 30% were assigned to the validation set (8,088 patients). A nomogram was constructed based on the results of the multivariate logistic regression analysis. The model performance was evaluated using the C statistic and the calibration performance was assessed by Hosmer-Lemeshow (HL) χ2 statistics and calibration plots.

Results

Multivariate logistic regression analyses revealed that female age, female body mass index (BMI), tubal factor infertility, male infertility, uterine factor infertility, unexplained infertility, antral follicle count (AFC) and basal serum follicle stimulating hormone (FSH) were significant factors for CLB in women undergoing the first IVF cycle. An area under the receiver operating characteristic curve (AUC) in the prediction model was 0.676 (95% CI 0.668 to 0.684) in the training group. The validation set showed possibly helpful discrimination with an AUC of 0.672 (95% CI 0.660 to 0.684). Additionally, the prediction model had a good calibration (HL χ2 = 8.240, P=0.410).

Conclusions

We developed and validated a nomogram to predict CLB in women undergoing the first IVF cycle using a single center database in China. The validated nomogram to predict CLB could be a potential tool for IVF counselling.
Evolutionary conservation of leptin effects on wound healing in vertebrates: Implications for veterinary medicine
Authors: Reeve Robyn E. , Quale Kyla , Curtis Grace H. , Crespi Erica J.
Published: August 2022

In mammals, the cytokine hormone leptin promotes wound healing by increasing inflammation, cellular recruitment, angiogenic regrowth, and re-epithelialization; however, it is not known whether leptin has conserved actions on wound healing in other vertebrates. Here, we tested the hypothesis that leptin promotes both the quality and speed of wound healing in the South African clawed frog, Xenopus laevis. First, fluorescent immunohistochemistry using a polyclonal antibody specific to Xenopus leptin showed that in juvenile dorsal skin, leptin protein is expressed in the dorsal epidermal layer, as well in blood vessel endothelial cells and sensory nerves that run along the base of the dermis. Injection of recombinant Xenopus leptin (rXleptin) stimulates phosphorylated STAT3 (pSTAT3), indicative of leptin-activated JAK/STAT signaling in the epidermis. Similar to mammals, leptin protein expression increases at the wound site after injury of the epidermis. We then cultured “punch-in-a-punch” full-thickness dorsal skin explants in three doses of rXleptin (0, 10, and 100 ng/ml) and showed that leptin treatment doubled the rate of wound closure after 48 h relative to skin punches cultured without leptin. Food restriction prior to wound explant culture reduced the amount of wound closure, but leptin injection prior to euthanasia rescued closure to similar control levels. Leptin treatment also significantly reduced bacterial infection of these epidermal punches by 48 h in culture. This study shows that leptin is likely an endogenous promoter of wound healing in amphibians. Leptin-based therapies have the potential to expedite healing and reduce the incidence of secondary infections without toxicity issues, the threat of antibiotic resistance, or environmental antibiotic contamination. The conservation of leptin’s actions on wound healing also suggests that it may have similar veterinary applications for other exotic species.
N-acetyl-L-cysteine treatment reduces beta-cell oxidative stress and pancreatic stellate cell activity in a high fat diet-induced diabetic mouse model
Authors: Schuurman Meg , Wallace Madison , Sahi Gurleen , Barillaro Malina , Zhang Siyi , Rahman Mushfiqur , Sawyez Cynthia , Borradaile Nica , Wang Rennian
Published: August 2022

Obesity plays a major role in type II diabetes (T2DM) progression because it applies metabolic and oxidative stress resulting in dysfunctional beta-cells and activation of intra-islet pancreatic stellate cells (PaSCs) which cause islet fibrosis. Administration of antioxidant N-acetyl-L-cysteine (NAC) in vivo improves metabolic outcomes in diet-induced obese diabetic mice, and in vitro inhibits PaSCs activation. However, the effects of NAC on diabetic islets in vivo are unknown. This study examined if dosage and length of NAC treatment in HFD-induced diabetic mice effect metabolic outcomes associated with maintaining healthy beta-cells and quiescent PaSCs, in vivo. Male C57BL/6N mice were fed normal chow (ND) or high-fat (HFD) diet up to 30 weeks. NAC was administered in drinking water to HFD mice in preventative treatment (HFDpNAC) for 23 weeks or intervention treatment for 10 (HFDiNAC) or 18 (HFDiNAC+) weeks, respectively. HFDpNAC and HFDiNAC+, but not HFDiNAC, mice showed significantly improved glucose tolerance and insulin sensitivity. Hyperinsulinemia led by beta-cell overcompensation in HFD mice was significantly rescued in NAC treated mice. A reduction of beta-cell nuclear Pdx-1 localization in HFD mice was significantly improved in NAC treated islets along with significantly reduced beta-cell oxidative stress. HFD-induced intra-islet PaSCs activation, labeled by αSMA, was significantly diminished in NAC treated mice along with lesser intra-islet collagen deposition. This study determined that efficiency of NAC treatment is beneficial at maintaining healthy beta-cells and quiescent intra-islet PaSCs in HFD-induced obese T2DM mouse model. These findings highlight an adjuvant therapeutic potential in NAC for controlling T2DM progression in humans.
Variation in intraocular pressure by sex, age, and geographic location in China: A nationwide study of 284,937 adults
Authors: Liu Xuan , Pan Xue , Ma Yuan , Jin Cheng , Wang Bo , Ning Yi
Published: August 2022

Objective

To investigate the distribution characteristics of intraocular pressure (IOP) by sex, age, and geographic location in China and to build the corresponding reference intervals (RIs).

Material and methods

A cross-sectional, multi-centered, population-based study was conducted. All data were collected from participants without eye diseases who underwent ophthalmological examinations in 170 Health Screening Centers in mainland China in 2018. The non-contact tonometer was used to measure IOP. The age-, sex-, and province-specific RIs of IOP were investigated. The IOP of different age–sex groups was further explored by stratifying according to height, body mass index (BMI), blood pressure, altitude, and geographic area.

Results

During the study, a population-based sample of 284,937 participants was included. The distribution of measured IOP followed an approximately Gaussian distribution, with a higher mean value in men than in women. The IOP showed a general trend of decline with age for both men and women and varied across geographical locations. The mean IOP was 15.4 (95% CI: 9.1-21.6) mmHg for men and 14.9 (95% CI: 9.0-20.8) mmHg for women. For men, it decreased from 11.0-23.5 mmHg at age 18-24 years to 10.5-20.5 mmHg at age ≥70 years. For women, it decreased from 10.5-22.0 to mmHg at age 18-24 years to 10.0-21.0 mm Hg at age ≥70 years.

Conclusions

The IOP varied with age, sex, metabolic disorders and geographic location. These RIs should be considered in the clinical process of glaucoma diagnosis and treatment.
Estrogen differentially regulates transcriptional landscapes of preoptic and arcuate kisspeptin neuron populations
Authors: Göcz Balázs , Takács Szabolcs , Skrapits Katalin , Rumpler Éva , Solymosi Norbert , Póliska Szilárd , Colledge William H. , Hrabovszky Erik , Sárvári Miklós
Published: August 2022

Kisspeptin neurons residing in the rostral periventricular area of the third ventricle (KPRP3V) and the arcuate nucleus (KPARC) mediate positive and negative estrogen feedback, respectively. Here, we aim to compare transcriptional responses of KPRP3V and KPARC neurons to estrogen. Transgenic mice were ovariectomized and supplemented with either 17β-estradiol (E2) or vehicle. Fluorescently tagged KPRP3V neurons collected by laser-capture microdissection were subjected to RNA-seq. Bioinformatics identified 222 E2-dependent genes. Four genes encoding neuropeptide precursors (Nmb, Kiss1, Nts, Penk) were robustly, and Cartpt was subsignificantly upregulated, suggesting putative contribution of multiple neuropeptides to estrogen feedback mechanisms. Using overrepresentation analysis, the most affected KEGG pathways were neuroactive ligand-receptor interaction and dopaminergic synapse. Next, we re-analyzed our previously obtained KPARC neuron RNA-seq data from the same animals using identical bioinformatic criteria. The identified 1583 E2-induced changes included suppression of many neuropeptide precursors, granins, protein processing enzymes, and other genes related to the secretory pathway. In addition to distinct regulatory responses, KPRP3V and KPARC neurons exhibited sixty-two common changes in genes encoding three hormone receptors (Ghsr, Pgr, Npr2), GAD-65 (Gad2), calmodulin and its regulator (Calm1, Pcp4), among others. Thirty-four oppositely regulated genes (Kiss1, Vgf, Chrna7, Tmem35a) were also identified. The strikingly different transcriptional responses in the two neuron populations prompted us to explore the transcriptional mechanism further. We identified ten E2-dependent transcription factors in KPRP3V and seventy in KPARC neurons. While none of the ten transcription factors interacted with estrogen receptor-α, eight of the seventy did. We propose that an intricate, multi-layered transcriptional mechanism exists in KPARC neurons and a less complex one in KPRP3V neurons. These results shed new light on the complexity of estrogen-dependent regulatory mechanisms acting in the two functionally distinct kisspeptin neuron populations and implicate additional neuropeptides and mechanisms in estrogen feedback.
Impact of acute hyperglycemic crisis episode on survival in individuals with diabetic foot ulcer using a machine learning approach
Authors: Deng Liling , Xie Puguang , Chen Yan , Rui Shunli , Yang Cheng , Deng Bo , Wang Min , Armstrong David G. , Ma Yu , Deng Wuquan
Published: August 2022

Objective

The outcome of DFUs concomitant with HCE remains unknown. This study aimed to investigate mortality rates and identify risk factors of mortality in patients with DFUs-HCE.

Methods

27 inpatients with DFUs-HCE were retrospectively enrolled in a cohort design, they were compared to 93 inpatients with DFUs in a city designated emergency center, between January 2016 and January 2021. After a 6-year followed-up, clinical characteristic, amputation and survival rates were compared. Extreme gradient boosting was further used to explore the relative importance of HCE and other risk factors to all-cause mortality in DFUs.

Results

Patients with DFUs-HCE were more likely to havedementia, acute kidney injury and septic shock, whereas DFUs were more likely to have diabetic peripheral neuropathy and ulcer recurrence (P<0.05). No significant difference was observed on the amputation rate and diabetes duration. Both Kaplan-Meier curves and adjusted Cox proportional model revealed that DFUs-HCE was associated with a higher mortality compared with DFUs (P<0.05). HCE significantly increased the risk of mortality in patients with DFUs (hazard ratio, 1.941; 95% CI 1.018-3.700; P = 0.044) and was independent from other confounding factors (age, sex, diabetes duration, Wagner grades and Charlson Comorbidity Index). The XGBoost model also revealed that HCE was one of the most important risk factors associated with all-cause mortality in patients with DFUs.

Conclusions

DFUs-HCE had significantly lower immediate survival rates (first 1-6 month) than DFUs alone. HCE is an important risk factor for death in DFUs patients.
Magnesium increases insulin-dependent glucose uptake in adipocytes
Authors: Oost Lynette J. , Kurstjens Steef , Ma Chao , Hoenderop Joost G. J. , Tack Cees J. , de Baaij Jeroen H. F.
Published: August 2022

Background

Type 2 diabetes (T2D) is characterized by a decreased insulin sensitivity. Magnesium (Mg2+) deficiency is common in people with T2D. However, the molecular consequences of low Mg2+ levels on insulin sensitivity and glucose handling have not been determined in adipocytes. The aim of this study is to determine the role of Mg2+ in the insulin-dependent glucose uptake.

Methods

First, the association of low plasma Mg2+ with markers of insulin resistance was assessed in a cohort of 395 people with T2D. Secondly, the molecular role of Mg2+ in insulin-dependent glucose uptake was studied by incubating 3T3-L1 adipocytes with 0 or 1 mmol/L Mg2+ for 24 hours followed by insulin stimulation. Radioactive-glucose labelling, enzymatic assays, immunocytochemistry and live microscopy imaging were used to analyze the insulin receptor phosphoinositide 3-kinases/Akt pathway. Energy metabolism was assessed by the Seahorse Extracellular Flux Analyzer.

Results

In people with T2D, plasma Mg2+ concentration was inversely associated with markers of insulin resistance; i.e., the lower Mg2+, the more insulin resistant. In Mg2+-deficient adipocytes, insulin-dependent glucose uptake was decreased by approximately 50% compared to control Mg2+condition. Insulin receptor phosphorylation Tyr1150/1151 and PIP3 mass were not decreased in Mg2+-deficient adipocytes. Live imaging microscopy of adipocytes transduced with an Akt sensor (FoxO1-Clover) demonstrated that FoxO1 translocation from the nucleus to the cytosol was reduced, indicting less Akt activation in Mg2+-deficient adipocytes. Immunocytochemistry using a Lectin membrane marker and at the membrane located Myc epitope-tagged glucose transporter 4 (GLUT4) demonstrated that GLUT4 translocation was diminished in insulin-stimulated Mg2+-deficient adipocytes compared to control conditions. Energy metabolism in Mg2+ deficient adipocytes was characterized by decreased glycolysis, upon insulin stimulation.

Conclusions

Mg2+ increases insulin-dependent glucose uptake in adipocytes and suggests that Mg2+ deficiency may contribute to insulin resistance in people with T2D.
A Model Predictive Controller for the Core Power Control System of a Lead-Cooled Fast Reactor
Authors: Hu Yang , Liang Lehua , Chen Lekang , Zeng Wenjie
Published: August 2022

To study the model predictive control (MPC) for a lead-cooled fast reactor's core power control system (LFR), firstly, the LFR core is established with the state space model. Then, to establish an LFR core power control system, a predictive model controller is used. Finally, the conditions of 20pcm step reactivity and 5% step down of coolant inlet temperature are introduced to study the control characteristic. The maximum overshot (MO) and the transient time are calculated in the time domain, and the stability of the core power control system is analyzed using the Nyquist and Bode diagrams in frequency domains. The result shows that the MPC controller and PID controller are feasible in core power control, and the core power control systems are closed-loop stable systems.
Plankton distribution patterns and the indicative significance of diverse cave wetlands in subtropical karst basin
Authors: Guo Fang , Jiang Guanghui , Liu Fan
Published: August 2022

In subtropical karst area, small wetlands are widely distributed owing to the well-developed karst and the high degree of groundwater-surface water interaction. However, detailed plankton community composition, spatial-temporal dynamics, and its assembly mechanism were rarely discussed. To address these, plankton distribution patterns and its relationship with hydrological conditions and environment gradients were analyzed to discover the biological characteristics of wetlands in a typical karst basin in South China. The results showed that the wetlands were diverse in types due to the hydrogeological background. Water quality evaluation according to major ions analyses showed good results, with significant differences among samples and a poor status when measured by biotic indicator such as Escherichia coli. During high and low-flow condition, a total of 163 and 162 species of phytoplankton, and a total of 62 and 36 species of zooplankton, respectively were observed. The dominant species of phytoplankton communities in low-flow condition metamorphosed from Cyclotella sp. to Navicula sp. and Cocconeis placentula; and Pediastrum simplex to Ankistrodesmus spiralis. The metamorphosis in zooplankton community was from Difflugia globulosa to Strobilidium sp. Comparing with other karst water in different climate regimes, the number of plankton species in the subtropical karst wetland was the highest, which is related to the high and stable water temperature, large karst underground spaces, and frequent interaction between groundwater and surface water. The abundance, biomass and community semblance of plankton were increased with an increase in nutrients, precipitating improvement in hydrodynamics and light intensity. This study also suggested that the plankton in karst cave wetlands in subtropical area were characterized by low diversity, attributable to the calcium-rich and weakly alkaline, but poor nutrient status of the water environment, as well as drew attention to the possible functions of wetlands in relation to the quality of connected river.
Whole mitochondrial genome analysis of Tai-Kadai-speaking populations in Southwest China
Authors: Feng Yuhang , Zhang Hongling , Wang Qiyan , Jin Xiaoye , Le Cuiyun , Liu Yubo , Wang Xiaoxue , Jiang Huang , Ren Zheng
Published: August 2022

As a single matrilineal gene, human mitochondrial DNA plays a very important role in the study of population genetics. The whole mitogenome sequences of 287 individuals of the Tai-Kadai-speaking population in Guizhou were obtained. It was discovered that there were 82, 104, and 94 haplotypes in 83 Bouyei individuals, 107 Dong individuals, and 97 Sui individuals, respectively; and the haplotype diversity in Bouyei, Dong, and Sui groups was 1.000 ± 0.02, 0.9993 ± 0.0015, and 0.999 ± 0.002, respectively. The result of neutrality tests of the Tai-Kadai-speaking population in Guizhou showed significant negative values, and the analysis of mismatch distribution showed an obvious unimodal distribution. The results implied that Guizhou Tai-Kadai-speaking populations had high genetic diversities and may have experienced recent population expansion. In addition, the primary haplogroups of studied populations were M*, F, B, D, and R*, implying that they may origin from Southern China. The matrilineal genetic structure of the Tai-Kadai-speaking populations in Guizhou was analyzed by merging the mitogenome data of 79 worldwide populations as reference data. The results showed that there were close relationships between studied populations and other Tai-Kadai as well as some Austronesian populations in East and Southeast Asia. Overall, the mitogenome data generated in this study will provide important data for the study of genetic structure of Tai-Kadai speaking populations.
Dental microwear texture analysis correlations in guinea pigs (Cavia porcellus) and sheep (Ovis aries) suggest that dental microwear texture signal consistency is species-specific
Authors: Martin Louise Françoise , Winkler Daniela Eileen , Ackermans Nicole Lauren , Müller Jaqueline , Tütken Thomas , Kaiser Thomas , Codron Daryl , Schulz-Kornas Ellen , Hatt Jean-Michel , Clauss Marcus
Published: August 2022

Dental microwear texture (DMT) analysis is used to differentiate abrasive dental wear patterns in many species fed different diets. Because DMT parameters all describe the same surface, they are expected to correlate with each other distinctively. Here, we explore the data range of, and correlations between, DMT parameters to increase the understanding of how this group of proxies records wear within and across species. The analysis was based on subsets of previously published DMT analyses in guinea pigs, sheep, and rabbits fed either a natural whole plant diet (lucerne, grass, bamboo) or pelleted diets with or without added quartz abrasives (guinea pigs and rabbits: up to 45 days, sheep: 17 months). The normalized DMT parameter range (P4: 0.69 ± 0.25; M2: 0.83 ± 0.16) and correlation coefficients (P4: 0.50 ± 0.31; M2: 0.63 ± 0.31) increased along the tooth row in guinea pigs, suggesting that strong correlations may be partially explained by data range. A comparison between sheep and guinea pigs revealed a higher DMT data range in sheep (0.93 ± 0.16; guinea pigs: 0.47 ± 0.29), but this did not translate into more substantial correlation coefficients (sheep: 0.35 ± 0.28; guinea pigs: 0.55 ± 0.32). Adding rabbits to an interspecies comparison of low abrasive dental wear (pelleted lucerne diet), the softer enamel of the hypselodont species showed a smaller data range for DMT parameters (guinea pigs 0.49 ± 0.32, rabbit 0.19 ± 0.18, sheep 0.78 ± 0.22) but again slightly higher correlations coefficients compared to the hypsodont teeth (guinea pigs 0.55 ± 0.31, rabbits 0.56 ± 0.30, sheep 0.42 ± 0.27). The findings suggest that the softer enamel of fast-replaced ever-growing hypselodont cheek teeth shows a greater inherent wear trace consistency, whereas the harder enamel of permanent and non-replaced enamel of hypsodont ruminant teeth records less coherent wear patterns. Because consistent diets were used across taxa, this effect cannot be ascribed to the random overwriting of individual wear traces on the more durable hypsodont teeth. This matches literature reports on reduced DMT pattern consistency on harder materials; possibly, individual wear events become more random in nature on harder material. Given the species-specific differences in enamel characteristics, the findings suggest a certain species-specificity of DMT patterns.
Determinants of rural household livelihood dependence on non-timber forest products: A case study from Inanda Community, KwaZulu-Natal, South Africa
Authors: Wale Edilegnaw , Nkoana Mmaphuti Andrias , Mkuna Eliaza
Published: August 2022

Natural forest resources are the most accessible sources of services, products and incomes for many adjacent rural communities. However, the declining resilience of forests and agricultural sectors particularly in South Africa is concerning and a real public policy challenge. Little is known about the determinants of rural community dependence on natural forests, and the importance of this dependence to rural livelihoods and environmental outcomes. This study investigated factors affecting rural household level of forest dependence and the contribution of natural forests to rural household livelihoods in the “KwaZulu-Natal Sandstone Sourveld (KZNSS)” ecosystem. Employing survey data from 150 forest-dependent households and a logit-transformed Ordinary Least Squares (OLS) model, the study found that there is significant level of forest dependence in the study area. The empirical findings showed that the contribution of forest resources to rural livelihoods is significantly influenced by off-farm incomes, employment incomes, forest vouchers received from the “Wildlands Project” in exchange for planting trees, values of household assets, changing of time and dates in visiting the forest for the collection of forest products, and perceived changes in temperature. These findings imply that institutional arrangements for programs like the “Wildlands Project” need to be developed from the beginning with the participation of all pertinent stakeholders for everyone to accept it and understand the regulations. Additionally, legislative changes are needed to help rural residents sustainably support their livelihoods and diversify their sources of income to build resilience and ease pressure on natural forests.
CircPUM1 Knockdown Confers Radiosensitivity in Oral Squamous Cell Carcinoma by Regulating the miR-580/STAT3 Pathway
Authors: Jia Linghui , Huang Pengcheng , Lin Tingting , Lin Chunyan , Ding Xiaofen , Lin Liping , Zhu Lifeng , Zhou Zhilian
Published: August 2022

Background: CircPUM1 acts as an oncogene in a variety of tumors, and there is no related research on oral squamous cell carcinoma. This study aimed to evaluate the clinical significance of CircPUM1 in oral squamous cell carcinoma radiotherapy.

Methods: Radio-resistant cell lines were established by increasing the X-ray dose. Analysis of CircPUM1 expression in oral squamous cell carcinoma was carried out using bioinformatics tools. Cell proliferation was analyzed with CCK-8 and colony formation. Protein and gene expressions were detected by Western blotting and qPCR. RNA interference inhibits endogenous gene expression. A luciferase reporter system and immunoprecipitation were used to validate the target of CircPUM1.

Result: CircPUM1 was highly expressed in OSCC. The higher the expression level of CircPUM1 in OSCC, the worse the clinical features and prognosis. Knockdown of CircPUM1 enhances the sensitivity of OSCC cells to X-rays, and expression of exogenous CircPUM1 makes OSCC cells acquire radiation resistance. The absence of CircPUM1 blocked the cells in the G0/G1 phase and triggered apoptosis. The prediction of mir-580-binding site, luciferase reporter system, and immunoprecipitation confirmed that mir-580 is the binding site of CircPUM1. In addition, STAT3 was predicted and confirmed as the binding site of mir-580. Overexpression of STAT3 partially attenuated the radiosensitivity of OSCC cells to knockdown of CircPUM1.

Conclusion: CircPUM1 has the oncogene expression profile in oral squamous cell carcinoma; patients with high expression of CircPUM1 have less benefit from radiotherapy and need more frequent follow-up. In addition, CircPUM1 may be a potential therapeutic target for oral squamous cell carcinoma. The CircPUM1/mir-580/STAT3 axis has a certain effect on the radiosensitivity of OSCC. These results suggest that patients with low expression of CircPUM1 may gain more benefits.
Genetic diversity and population structure of Tongcheng pigs in China using whole-genome SNP chip
Authors: Yuan Jiao , Zhou Xiang , Xu Guoqiang , Xu Sanping , Liu Bang
Published: August 2022

Tongcheng (TC) pigs, distinguished by their superior meat quality, are a Chinese indigenous pig breed. Recently, the genetic resources of TC pigs are under tremendous threat due to the introduction of cosmopolitan pig breeds and African swine fever disease. To promote their management and conservation, the present study assessed genetic diversity and population structure of TC pigs using single nucleotide polymorphism (SNP) markers. A total of 26, 999 SNPs were screened from 51, 315 SNPs in 68 TC pigs. The multi-dimensional scaling (MDS) analysis and neighbor-joining tree revealed that all 68 pigs were from a purebred population. The effective population size decreased over time, and it was 96 prior to generation 20. Both linkage disequilibrium (LD) and neutrality test indicated a low selection of TC pigs with average LD value of 0.15 ± 0.23. Genetic diversity results exhibited a minor allele frequency (MAF) of 0.23, observed heterozygosity (HO) of 0.32, expected heterozygosity (He) of 0.31, and nucleotide diversity (Pi) of 0.31. All these parameters indicated a remarkably high genetic diversity of TC pigs. Additionally, 184 runs of homozygosity (ROH) segments were detected from the whole genome of TC pigs with an average ROH length of 23.71Mb, ranging from 11.26Mb to 69.02 Mb. The highest ROH coverage was found on chromosome 1 (10.12%), while the lowest was on chromosome 18 (1.49%). The average inbreeding coefficients based on ROH (FROH) was 0.04%. Fourteen ROH islands containing 240 genes were detected on 9 different autosomes. Some of these 240 genes were overlapped with the genes related to biological processes such as immune function, reproduction, muscular development, and fat deposition, including FFAR2, FFAR4, MAPK8, NPY5R, KISS1, and these genes might be associated with such traits as meat quality and disease resistance in TC pigs. Taken together, population structure and genetic diversity results suggested that the TC pig represented a valuable genetic resource. However, TC pig breed conservation program remains to be further optimized to ensure adequate genetic diversity and avoid inbreeding depression. Our findings provide theoretical basis for formulating management and conservation strategies for TC pigs.
Case Report: Diverse phenotypes of congenital poikiloderma associated with FAM111B mutations in codon 628: A case report and literature review
Authors: Wu Yuhao , Wen Long , Wang Peiru , Wang Xiuli , Zhang Guolong
Published: August 2022

Congenital poikiloderma is an extremely rare autosomal dominant genetic syndrome, characterized by a combination of early onset poikiloderma, telangiectasia, and epidermal atrophy. FAM111B gene with multiple mutations has been identified as a potential causative gene for congenital poikiloderma. In this report, we described a boy with congenital poikiloderma confirmed by clinical manifestations. Next-generation sequencing based on a gene probe panel consisting of 541 genetic loci of genodermatoses, was used to screen mutations of the proband and his parents. Results showed that a missense mutation in the FAM111B gene c.1883G>A (rs587777238) was identified in the proband, but absent in his parents, indicating the mutation is de novo. In conclusion, a new case of congenital poikiloderma in China was reported, and the hotspot mutations in codon 628 of FAM111B gene was reviewed, as well as authenticating the uncertain association between genotypes and phenotypes in this rare disease.
Comprehensive characterization of pharmacogenes in a Taiwanese Han population
Authors: Lu Hsing-Fang , Liu Ting-Yuan , Chou Yu-Pao , Chang Shih-Sheng , Hsieh Yow-Wen , Chang Jan-Gowth , Tsai Fuu-Jen
Published: August 2022

Pharmacogenetic (PGx) testing has not been well adopted in current clinical practice. The phenotypic distribution of clinically relevant pharmacogenes remains to be fully characterized in large population cohorts. In addition, no study has explored actionable PGx alleles in the East Asian population at a large scale. This study comprehensively analyzed 14 actionable pharmacogene diplotypes and phenotypes in 172,854 Taiwanese Han individuals by using their genotype data. Furthermore, we analyzed data from electronic medical records to investigate the effect of the actionable phenotypes on the individuals. The PGx phenotype frequencies were comparable between our cohort and the East Asian population. Overall, 99.9% of the individuals harbored at least one actionable PGx phenotype, and 29% of them have been prescribed a drug to which they may exhibit an atypical response. Our findings can facilitate the clinical application of PGx testing and the optimization of treatment and dosage individually.
A novel cuproptosis-related gene signature for predicting prognosis in cervical cancer
Authors: Lei Lei , Tan Liao , Sui Long
Published: August 2022

Purpose: Cuproptosis, a form of copper-induced cell death, can be a promising therapeutic target for refractory cancers. Hence, we conducted this research to explore the association between cuproptosis and prognosis in cervical cancer (CC).

Methods: For constructing a prognostic signature based on cuproptosis-related genes from TCGA database, the least absolute shrinkage and selection operator Cox regression was utilized. The GSE44001 cohort was utilized for validation.

Results: A total of nine cuproptosis-related genes showed distinct expression in CC and normal samples in TCGA-GTEx cohort. Two risk groups were identified based on a seven-gene signature. A significant decrease in overall survival was observed in the high-risk group (p < 0.001). The risk score (HR = 2.77, 95% CI = 1.58–4.86) was an autocephalous predictor with a better predictive ability than the clinical stage. Functional analysis indicated that immune activities were suppressed more in the high-risk group than in the low-risk group. A total of 11 candidate compounds targeting the signature were identified.

Conclusion: A total of seven cuproptosis-related gene signatures were constructed to predict prognosis and propose a new therapeutic target for patients with CC.
Comprehensive exploration of tumor immune microenvironment feature and therapeutic response in colorectal cancer based on a novel immune-related long non-coding RNA prognostic signature
Authors: Zhou Xueliang , Aikemu Batuer , Li Shuchun , Shao Yanfei , Jia Hongtao , Huang Ling , Hong Hiju , Zhang Sen , Tang Qiushi , Pan Ruijun , Sun Jing , Zheng Minhua
Published: August 2022

Colorectal cancer (CRC) is one of the most common malignant tumors with a high incidence rate and mortality. LncRNA is an important regulator of the immune system. It is of great significance to study immune-related lncRNAs (IR-lncRNAs) for CRC. In this study, we screened IR-lncRNAs differentially expressed in normal and CRC tissues, and Univariate Cox regression and the Least Absolute Shrinkage and Selection Operator were applied to construct IR-lncRNA prognostic signature in TCGA training dataset, and its predictive capability for the prognosis of CRC patients was verified in GSE39582 validation dataset. The novel signature was identified as an independent predictor of prognosis in CRC patients. In addition, the signature could accurately predict the feature of the immune microenvironment and therapeutic response in CRC patients. The CMap database was adopted to screen for small molecule candidate drugs that can reverse and treat high-risk CRC patients. Finally, the expression of six IR-lncRNAs were verified by qRT-PCR in clinical specimens from our patient cohort. In conclusion, we construct an IR-lncRNA prognostic signature, which is a powerful biomarker of CRC and can accurately predict the prognosis, immune microenvironment feature, and therapeutic response of CRC patients.