bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential Diagnosis of Fulminant Myocarditis and Acute Coronary Syndromes in the Case of Failure of Coronary Angiography: A Case Report
Authors: Huang Xiangfei , Gao Yi , Hua Fuzhou , Ying Jun
Published: December 2021

Fulminant myocarditis (FM) is a severe disease with a rapidly progressive and life-threatening course caused mainly by viral infection. The symptoms, laboratory findings, and presence of ECG changes resemble acute coronary syndrome. Therefore, coronary angiography is usually helpful in making the appropriate diagnosis. However, failure to obtain complete coronary artery images due to coronary artery anatomic variations poses a challenge for the diagnosis of FM. Here, we report a case of FM preliminarily diagnosed as acute coronary syndrome (ACS) due to the presence of coronary artery anomaly.
Association Between Serum Calcium and the Prevalence of Hypertension Among US Adults
Authors: Hua Yang , Liu Heng-li , Sun Jin-Yu , Kong Xiang-Qing , Sun Wei , Xiong Ya-Qing
Published: December 2021

Background: Hypertension is a significant risk factor of cardiovascular diseases, posing a serious threat to global health. Calcium plays an important role in regulating body homeostasis. The association of calcium with hypertension remains uncertain in the general population.

Methods and Results: Cross-sectional data from the 2007–2018 National Health and Nutrition Examination Survey (NHANES) were analyzed. Adjusted multivariable logistic regression analysis and restricted cubic spline were used to investigate the association of serum calcium with the prevalence of hypertension. A total of 26,778 participants were included. The increase in calcium levels showed a positive association with the prevalence of hypertension in all three models with ORs of 1.347 (1.249–1.454), 1.522 (1.401–1.654), and 1.438 (1.306–1.583). The further subgroup analysis demonstrated a robust trend across all categories by sex, age, race, BMI, and eGFR. The restricted cubic spline plot exhibited an S-curve relationship between calcium and hypertension.

Conclusion: Our cross-sectional study demonstrated a positive association between higher serum calcium level and the prevalence of hypertension. Our findings highlighted serum calcium level in hypertensive patients.
Isoproterenol-Induced Cardiomyopathy Recovery Intervention: Amlexanox and Forskolin Enhances the Resolution of Catecholamine Stress-Induced Maladaptive Myocardial Remodeling
Authors: Adzika Gabriel Komla , Hou Hongjian , Adekunle Adebayo Oluwafemi , Rizvi Ruqayya , Adu-Amankwaah Joseph , Shang Wenkang , Li Kexue , Deng Qi-Ming , Mprah Richard , Ndzie Noah Marie Louise , Sun Hong
Published: November 2021

The increasing incidence of stress-induced cardiomyopathy is due to the complexities of our modern-day lives, which constantly elicit stress responses. Herein, we aimed to explore the therapeutic potential of Amlexanox and Forskolin in promoting the recovery from stress-induced cardiomyopathy. Isoproterenol-induced cardiomyopathy (ICM) models were made, and the following treatment interventions were administered: 5% v/v DMSO as a placebo, Amlexanox (2.5 mg/100 g/day) treatment, Forskolin (0.5 mg/100 g/day), and Amlexanox and Forskolin combination, at their respective aforementioned dosages. The effects of Amlexanox and Forskolin treatment on ICM models were assessed by eletrocardiography and echocardiography. Also, using histological analysis and ELISA, their impact on myocardial architecture and inflammation were ascertained. ICM mice had excessive myocardial fibrosis, hypertrophy, and aggravated LVSDs which were accompanied by massive CD86+ inflammatory cells infiltration. Amlexanox treatment attenuated the myocardial hypertrophy, fibrosis, and inflammation and also slightly improved systolic functions. Meanwhile, forskolin treatment resulted in arrhythmias but significantly enhanced the resolution of myocardial fibrosis and inflammation. Intriguingly, Amlexanox and Forskolin combination demonstrated the most potency at promoting the recovery of the ICM from LVSD by attenuating maladaptive myocardial hypertrophy, fibrosis, and inflammatory responses. Our findings highlight the Amlexanox and Forskolin combination as a potential therapeutic intervention for enhancing cardiac function recovery from stress-induced cardiomyopathy by promoting the resolution of maladaptive cardiac remodeling.
Influence of Dexmedetomidine on Post-operative Atrial Fibrillation After Cardiac Surgery: A Meta-Analysis of Randomized Controlled Trials
Authors: Peng Sheng , Wang Juan , Yu Hui , Cao Ge , Liu Peirong
Published: November 2021

Background: Previous clinical studies and meta-analysis evaluating the influence of dexmedetomidine on postoperative atrial fibrillation showed inconsistent results. We performed an updated meta-analysis to evaluate the influence of dexmedetomidine on incidence of postoperative atrial fibrillation after cardiac surgery.

Methods: Randomized controlled trials that evaluated the potential influence of dexmedetomidine on the incidence of atrial fibrillation after cardiac surgery were obtained by search of PubMed, Embase, and Cochrane's Library databases from inception to April 12, 2021. A random-effects model incorporating the potential publication bias was used to pool the results. Influences of patient or study characteristics on the efficacy of dexmedetomidine on atrial fibrillation after cardiac surgery were evaluated by meta-regression and subgroup analyses.

Results: Fifteen studies with 2,733 patients were included. Pooled results showed that dexmedetomidine significantly reduced the incidence of atrial fibrillation compared to control (OR: 0.72, 95% CI: 0.55–0.94, p = 0.02) with mild heterogeneity (I2 = 26%). Subgroup analysis showed that dexmedetomidine significantly reduced the incidence of atrial fibrillation in studies from Asian countries (OR: 0.41, 95% CI: 0.26–0.66, p < 0.001), but not in those from non-Asian countries (OR: 0.89, 95% CI: 0.71–1.10, p = 0.27; p for subgroup difference = 0.004). Meta-regression analysis showed that the mean age and proportion of male patients may modify the influence of dexmedetomidine on POAF (coefficient = 0.028 and 0.021, respectively, both p < 0.05). Subgroup analysis further showed that Dex was associated with reduced risk of atrial fibrillation after cardiac surgery in studies with younger patients (mean age ≤ 61 years, OR = 0.44, 95% CI: 0.28–0.69, p = 0.004) and smaller proportion of males (≤74%, OR = 0.55, 95% CI: 0.36–0.83, p = 0.005), but not in studies with older patients or larger proportion of males (p for subgroup difference = 0.02 and 0.04).

Conclusions: Current evidence supports that perioperative administration of dexmedetomidine may reduce the risk of incidental atrial fibrillation after cardiac surgery, particularly in Asians.
Gut Metabolite Trimethylamine-N-Oxide in Atherosclerosis: From Mechanism to Therapy
Authors: Wang BingYu , Qiu Jun , Lian JiangFang , Yang Xi , Zhou JianQing
Published: November 2021

Atherosclerosis is associated with various pathological manifestations, such as ischemic heart disease, ischemic stroke, and peripheral arterial disease, and remains a leading cause of public health concern. Atherosclerosis is an inflammatory disease characterized by endothelial dysfunction; vascular inflammation; and the deposition of lipids, cholesterol, calcium, and cellular debris within the vessel wall intima. In-depth studies of gut flora in recent years have shown that bacterial translocation and the existence of bacterial active products in blood circulation can affect the inflammatory state of the whole blood vessel. The gut flora is considered to be a large “secretory organ,” which produces trimethylamine-N-oxide (TMAO), short-chain fatty acids and secondary bile acids by breaking down the ingested food. Studies have shown that TMAO is an independent risk factor for the occurrence of malignant adverse cardiovascular events, but whether it is harmful or beneficial to patients with cardiovascular diseases with mild or no clinical manifestations remains controversial. We review the relationship between TMAO and its precursor (L-carnitine) and coronary atherosclerosis and summarize the potential molecular mechanism and therapeutic measures of TMAO on coronary atherosclerosis.
The Associations of Lipid Profiles With Cardiovascular Diseases and Death in a 10-Year Prospective Cohort Study
Authors: Dong Jiayi , Yang Song , Zhuang Qian , Sun Junxiang , Wei Pengfei , Zhao Xianghai , Chen Yanchun , Chen Xiaotian , Li Mengxia , Wei Lai , Chen Changying , Fan Yao , Shen Chong
Published: November 2021

Background: Dyslipidemia is one of the modifiable risk factors for cardiovascular diseases (CVD). Identifying subjects with lipid abnormality facilitates preventative interventions.

Objectives: To evaluate the effects of lipid indices on the risks of ischemic stroke (IS), coronary heart disease (CHD), CVD, all-cause death, and CVD death.

Methods: The cohort study of 4,128 subjects started in May 2009 and followed up to July 2020. Restricted cubic spline (RCS) regression analysis was used to explore the dose-response relationship between lipid indices with outcomes. Cox proportional hazard regression analysis was used to estimate the association with a hazard ratio (HR) and 95% CI.

Results: RCS analysis showed that there were significant linear associations of TG with IS, non-high-density lipoprotein cholesterol (HDL-C), apolipoprotein B (ApoB), and total cholesterol (TC)/HDL-C ratio with all-cause death, non-HDL-C and RC with CVD death, and significant non-linear associations of ApoB with IS and CVD, TC, LDL-C, ApoAI, and TC/HDL-C ratio with CHD, and TC with all-cause death (all P <0.1). Cox regression analysis revealed that subjects with TC <155 mg/dl (vs. 155–184 mg/dl), > 185 mg/dl (vs. 155–184 mg/dl), and ApoB <0.7 g/l (vs. ≥0.7 g/l) had higher risks of CHD (P < 0.05), the adjusted HRs (95% CIs) were 1.933 (1.248–2.993), 1.561 (1.077–2.261), and 1.502 (1.01–2.234), respectively. Subjects with ApoAI > 2.1 g/l (vs. 1.6–2.1 g/l) and TG <80 mg/dl (vs. 80–177 mg/dl) had higher risks of CVD and all-cause death (P < 0.05), the adjusted HRs (95% CIs) were 1.476 (1.031–2.115) and 1.234 (1.002–1.519), respectively.

Conclusions: Lower or higher levels of TC, higher level of ApoAI, and lower level of ApoB were associated with increased risks of CVD, and lower level of TG was associated with increased all-cause death. Maintaining optimal lipid levels would help to prevent CVD and reduce mortality.
ΔPCO2 and ΔPCO2/C(a−cv)O2 Are Not Predictive of Organ Dysfunction After Cardiopulmonary Bypass
Authors: Zhang Sheng , Zheng Dan , Chu Xiao-Qiong , Jiang Yong-Po , Wang Chun-Guo , Zhang Qiao-Min , Qian Lin-Zhu , Yang Wei-Ying , Zhang Wen-Yuan , Tung Tao-Hsin , Lin Rong-Hai
Published: December 2021

Background: Cardiac surgery is associated with a substantial risk of major adverse events. Although carbon dioxide (CO2)-derived variables such as venous-to-arterial CO2 difference (ΔPCO2), and PCO2 gap to arterial–venous O2 content difference ratio (ΔPCO2/C(a−cv)O2) have been successfully used to predict the prognosis of non-cardiac surgery, their prognostic value after cardiopulmonary bypass (CPB) remains controversial. This hospital-based study explored the relationship between ΔPCO2, ΔPCO2/C(a−cv)O2 and organ dysfunction after CPB.

Methods: We prospectively enrolled 114 intensive care unit patients after elective cardiac surgery with CPB. Patients were divided into the organ dysfunction group (OI) and non-organ dysfunction group (n-OI) depending on whether organ dysfunction occurred or not at 48 h after CPB. ΔPCO2 was defined as the difference between central venous and arterial CO2 partial pressure.

Results: The OI group has 37 (32.5%) patients, 27 of which (23.7%) had one organ dysfunction and 10 (8.8%) had two or more organ dysfunctions. No statistical significance was found (P = 0.84) for ΔPCO2 in the n-OI group at intensive care unit (ICU) admission (9.0, 7.0–11.0 mmHg), and at 4 (9.0, 7.0–11.0 mmHg), 8 (9.0, 7.0–11.0 mmHg), and 12 h post admission (9.0, 7.0–11.0 mmHg). In the OI group, ΔPCO2 also showed the same trend [ICU admission (9.0, 8.0–12.8 mmHg) and 4 (10.0, 7.0–11.0 mmHg), 8 (10.0, 8.5–12.5 mmHg), and 12 h post admission (9.0, 7.3–11.0 mmHg), P = 0.37]. No statistical difference was found for ΔPCO2/C(a−cv)O2 in the n-OI group (P = 0.46) and OI group (P = 0.39). No difference was detected in ΔPCO2, ΔPCO2/C(a−cv)O2 between groups during the first 12 h after admission (P > 0.05). Subgroup analysis of the patients with two or more failing organs compared to the n-OI group showed that the predictive performance of lactate and Base excess (BE) improved, but not of ΔPCO2 and ΔPCO2/C(a−cv)O2. Regression analysis showed that the BE at 8 h after admission (odds ratio = 1.37, 95%CI: 1.08–1.74, P = 0.009) was a risk factor for organ dysfunction 48 h after CBP.

Conclusion : ΔPCO2 and ΔPCO2/C(a−cv)O2 cannot be used as reliable indicators to predict the occurrence of organ dysfunction at 48 h after CBP due to the pathophysiological process that occurs after CBP.
Higher Incidence of Stroke in Severe COVID-19 Is Not Associated With a Higher Burden of Arrhythmias: Comparison With Other Types of Severe Pneumonia
Authors: Jirak Peter , Shomanova Zornitsa , Larbig Robert , Dankl Daniel , Frank Nino , Seelmaier Clemens , Butkiene Dominyka , Lichtenauer Michael , Mirna Moritz , Strohmer Bernhard , Sackarnd Jan , Hoppe Uta C. , Sindermann Jürgen , Reinecke Holger , Frommeyer Gerrit , Motloch Lukas J. , Pistulli Rudin
Published: November 2021

Aims: Thromboembolic events, including stroke, are typical complications of COVID-19. Whether arrhythmias, frequently described in severe COVID-19, are disease-specific and thus promote strokes is unclear. We investigated the occurrence of arrhythmias and stroke during rhythm monitoring in critically ill patients with COVID-19, compared with severe pneumonia of other origins.

Methods and Results: This retrospective study included 120 critically ill patients requiring mechanical ventilation in three European tertiary hospitals, including n =60 COVID-19, matched according to risk factors for the occurrence of arrhythmias in n = 60 patients from a retrospective consecutive cohort of severe pneumonia of other origins. Arrhythmias, mainly atrial fibrillation (AF), were frequent in COVID-19. However, when compared with non-COVID-19, no difference was observed with respect to ventricular tachycardias (VT) and relevant bradyarrhythmias (VT 10.0 vs. 8.4 %, p = ns and asystole 5.0 vs. 3.3%, p = ns) with consequent similar rates of cardiopulmonary resuscitation (6.7 vs. 10.0%, p = ns). AF was even more common in non-COVID-19 (AF 18.3 vs. 43.3%, p = 0.003; newly onset AF 10.0 vs. 30.0%, p = 0.006), which resulted in a higher need for electrical cardioversion (6.7 vs. 20.0%, p = 0.029). Despite these findings and comparable rates of therapeutic anticoagulation (TAC), the incidence of stroke was higher in COVID-19 (6.7.% vs. 0.0, p = 0.042). These events also happened in the absence of AF (50%) and with TAC (50%).

Conclusions: Arrhythmias were common in severe COVID-19, consisting mainly of AF, yet less frequent than in matched pneumonia of other origins. A contrasting higher incidence of stroke independent of arrhythmias also observed with TAC, seems to be an arrhythmia-unrelated disease-specific feature of COVID-19.
A Case Report: An Elderly Male Patient With Takayasu Arteritis After Coronary Artery Bypass Grafting
Authors: Yu Huaitao , Liu Wenzhao , Zhang Yuan , Yan Xuefang , Li Na , Ti Yun , Bu Peili
Published: November 2021

Background: Takayasu arteritis is a rare chronic granulomatous inflammation involving the aorta and its main branches. In this report, we describe an extremely rare elderly male patient with Takayasu arteritis (TA) after coronary artery bypass grafting (CABG).

Case Summary: A 61-year-old male patient with persistent precordial pain underwent angiography. Vascular murmurs could be heard in carotid artery and bilateral renal artery by auscultation. Laboratory parameters showed high Erythrocyte Sedimentation Rate (ESR) and C-reactive protein (CRP). CT coronary angiography showed multiple stenoses of aorta and its main branches, such as carotid and renal artery involvement. Coronary angiography showed that the coronary artery had multiple branch stenoses, the left anterior descending artery (LAD) had severe stenosis, the distal end of which was reversed to the right coronary artery (RCA), and the RCA was completely occluded. Because of the high level of markers of inflammatory activity, the patient began to take glucocorticoid. Although the patient still had multibranch stenosis of coronary artery, considering the previous CABG operation history, surgery, and interventional therapy of the patient were not feasible, the patient was given conservative drug for further treatment. After treatment, the inflammatory index was significantly descended, and N terminal-pro Brain natriuretic peptide (NT-pro BNP) was decreased.

Discussion: A rare case of an elderly male patient with Takayasu arteritis after coronary artery bypass grafting was reported. In addition to hypertension, hyperlipidemia, and other risk factors, coronary artery involvement caused by TA may be a major cause of aggravation of symptoms in patients with acute myocardial infarction (AMI), especially after CABG.
Effect of Sodium Tanshinone IIA Sulfonate Injection on Blood Lipid in Patients With Coronary Heart Disease: A Systematic Review and Meta-Analysis of Randomized Clinical Trials
Authors: Zhou Hufang , Zhao Ying , Peng Wenhua , Han Wenbo , Wang Zichen , Ren Xiaoxia , Wang Dayang , Pan Guozhong , Lin Qian , Wang Xian
Published: November 2021

Background: Lipid-lowering therapy is very important in secondary prevention of coronary heart disease (CHD). In many clinical trials, it has been found that Sodium Tanshinone IIA Sulfonate Injection (STS) have a lipid-lowering effect while reducing major cardiovascular events in patients with CHD. However, up to now, there is no system review on the effectiveness and safety of STS affecting blood lipids.

Purpose: The aim of this review is to systematically assess the effects of STS on blood lipid levels in patients with CHD.

Methods: Until Mar 2021, five databases (PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, and Wanfang Database) were searched for randomized controlled trials (RCTs) about STS treating patients with CHD. Risk bias was assessed for included studies according to Cochrane handbook. The primary outcome was total cholesterol (TC). The secondary outcomes were triglycerides (TG), low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), and adverse events (AEs).

Results: A total of 27 trials including 2,445 CHD patients met the eligibility criteria. Most trials had high risks in random sequence generation, allocation concealment, blinding of patients and personal, blinding of outcome assessment. Meta-analysis showed that STS significantly reduced plasma TC levels [MD = −1.34 mmol/l 95% CI (−1.59, −1.09), p < 0.00001, I2 = 98%], TG levels [MD = −0.49 mmol/l 95% CI (−0.62, −0.35), p < 0.00001, I2 = 97%], LDL-c levels [MD = −0.68 mmol/l (−0.80, −0.57), p < 0.00001, I2 = 96%], increased HDL-c levels [MD = 0.26 mmol/l (0.15, 0.37), p < 0.00001, I2 = 97%], without increasing the incidence of AEs [RR = 1.27 95% CI (0.72, 2.27), p = 0.94, I2 = 0%] in patients with CHD.

Conclusion: STS can safely and effectively reduce plasma TC, TG and LDL-c levels in patients with CHD, and improve plasma HDL-c levels. However, these findings require careful recommendation due to the low overall quality of RCTs at present. More multi-center, randomized, double-blind, placebo-controlled trials which are designed follow the CONSORT 2010 guideline are needed.
Statin Therapy in Very Old Patients: Lights and Shadows
Authors: Cobos-Palacios Lidia , Sanz-Cánovas Jaime , Muñoz-Ubeda Mónica , Lopez-Carmona María Dolores , Perez-Belmonte Luis Miguel , Lopez-Sampalo Almudena , Gomez-Huelgas Ricardo , Bernal-Lopez Maria Rosa
Published: December 2021

Atherosclerotic cardiovascular diseases (ASCVD) are the leading cause of death worldwide. High levels of total cholesterol—and of low-density lipoprotein cholesterol in particular—are one of the main risk factors associated with ASCVD. Statins are first-line treatment for hypercholesterolemia and have been proven to reduce major vascular events in adults with and without underlying ASCVD. Findings in the literature show that statins reduce coronary and cerebrovascular morbidity and mortality in middle-aged people, but their benefits in older adults are not as well-established, especially in primary prevention. Furthermore, many particularities must be considered regarding their use in old subjects, such as age-related changes in pharmacokinetics and pharmacodynamics, comorbidities, polypharmacy, and frailty, which decrease the safety and efficacy of statins in this population. Myopathy and a possible higher risk of falling along with cognitive decline are classic concerns for physicians when considering statin use in the very old. Additionally, some studies suggest that the relative risk for coronary events and cardiovascular mortality associated with high levels of cholesterol decreases after age 70, making the role of statins unclear. On the other hand, ASCVD are one of the most important causes of disability in old subjects, so cardiovascular prevention is of particular interest in this population in order to preserve functional status. This review aims to gather the current available evidence on the efficacy and safety of statin use in very old patients in both primary and secondary prevention.
Exploring the Pool of Pathogenic Variants of Amelogenesis Imperfecta: An Approach to the Understanding of Its Genetic Architecture
Authors: Urzúa Blanca , Ortega-Pinto Ana , Adorno-Farias Daniela , Morales-Bozo Irene , Rojas-Flores Sandra , Briones-Marín Diego , Lepiman-Torres Constanza
Published: December 2021

Objective: To identify which genes are associated with the clinical phenotype of amelogenesis Imperfecta (AI) and to elucidate which of these genes participate in the determination of isolated and syndromic forms.

Methods: In this review, all data on mutations described in AI-related genes were obtained from HGMD® Professional. The data in relation to the mutations, inheritance, phenotype, type of AI and country were supplemented with information from the literature. The identity codes and frequency values were obtained from the dbSNP, ClinVar and OMIM databases. The percentage of specificity (PE) was determined for each gene.

Results: HGMD® describes 27 genes involved in AI, which we propose to group into 5 categories: (1) genes whose mutations are associated only with isolated AI, (2) genes whose mutations cause only syndromic AI, (3) genes with both mutations that cause isolated AI and mutations responsible for other pathologies, (4) genes with mutations responsible for syndromic AI and mutations that cause other pathologies, and (5) genes with mutations that cause isolated AI and mutations that cause AI associated with syndromes and other pathologies. Using the PE calculation, the genes were ranked into 5 specificity groups. The genes of category 1 are specific for isolated AI, while the genes of categories 2 and 4 are non-specific. Interestingly, we observed that mutations in some genes were associated with different types of cancer.

Conclusion: The ACP4, AMTN, MMP20, ODAPH, RELT, SLC24A4 and SP6 genes participate in causing isolated AI, and the CNNM4, DLX3 and FAM20A genes participate in causing syndromic forms of AI.
Relationship Between Altimetric Quality and Along-Track Spatial Resolution for iGNSS-R Sea Surface Altimetry: Example for the Airborne Experiment
Authors: Liu Zongqiang , Zheng Wei , Wu Fan , Kang Guohua , Sun Xuezhi , Wang Qiang
Published: November 2021

The altimetric quality and the along-track spatial resolution are the critical parameters to characterize the performance of interferometric global navigation satellite systems reflectometry (iGNSS-R) sea surface altimetry, which is closely related to each other through signal processing time. Among them, the quality of sea surface height (SSH) measurement includes precision and accuracy. In order to obtain higher altimetric quality in the observation area, a longer signal processing time is needed, which will lead to the loss of spatial resolution along the track. In contrast, higher along-track spatial resolution requires more intensive sampling, leading to unsatisfactory altimetric quality. In this study, taking the airborne iGNSS-R observation data as an example, the relationship between the altimetric quality and the along-track spatial resolution is analyzed from the perspectives of precision and accuracy. The results indicate that the reduction in the along-track spatial resolution will improve the altimetric quality. The accuracy range is 0.28–0.73 m, and the precision range is 0.24–0.65 m. However, this change is not linear, and the degree of altimetric quality improvement will decrease as the along-track spatial resolution worsens. The research results in this paper can provide a scientific reference for the configuration of parameters for future spaceborne iGNSS-R altimetry missions.
Geochemical and Mineralogical Characteristics of Garnierite From the Morowali Ni-Laterite Deposit in Sulawesi, Indonesia
Authors: Choi Yuri , Lee Insung , Moon Inkyeong
Published: November 2021

The Morowali Ni-laterite deposit is located in the East Sulawesi Ophiolite, which is a large ophiolite belt on Sulawesi Island, Indonesia. The Morowali deposit is developed on a laterite profile due to ophiolite weathering, with saprolite, limonite, and ferruginous cap horizons from the bottom to top. Based on the occurrence of garnierite as the main ore, occurring in the saprolite horizon, it can be classified that the ore deposit is hydrous Mg silicate-type. The Ni ore is classified into different types based on color and XRD and electron probe micro-analyzer analyses. Whole-rock geochemical study was also conducted to understand the mineralization process. The Morowali Ni deposit consists of serpentine-like and talc-like phases. The serpentine-like phase consists of Ni-lizardite and karpinskite (0.76–38.26 wt% NiO) while the talc-like phase is mainly composed of kerolite (4.02–8.02 wt% NiO). The serpentine-like garnierite exhibits high Ni and Fe contents and occurrence similar to that of the serpentine observed in the saprolite horizon, suggesting the serpentine-like garnierite originated from the bedrock, and Mg-Ni cation exchange occurred during laterization. Contrastingly, the lower Fe content of the talc-like phase (0.01–0.05 wt%) than the serpentine-like phase (0.14–7.03 wt%) indicates that the talc-like garnierite is of secondary origin since Fe is immobile during weathering. The Morowali Ni-laterite deposit was mainly formed during laterization. The repetition of dry and wet cycles in each year results in the formation of secondary garnierite.
Porosity Evolution In Lacustrine Organic-Matter-Rich Shales With High Claly Minerals Content
Authors: Jiang Xiaohua , Wu Songtao , Hou Lianhua , Zhang Jinyou , Guan Modi , Zhai Fulin , Guo Jinhao , Su Ling , Liao Fengrong , Ding Lihua
Published: November 2021

Pore structure is a major factor affecting the storage space and oil-bearing properties of shales. Mineralogy, organic matter content, and thermal evolution complicate the pore structures of lacustrine shales. In this study, the porosity evolution of organic-matter-rich shales from the Cretaceous Nenjiang Formation in the Songliao Basin, Northeast China, are investigated using thermal simulation experiments and in-situ scanning electron microscope analysis. Three findings were obtained as follows: 1) The pore system of shales from the Nenjiang Formation is dominated by inter-granular dissolution pores of plagioclase and intra-granular pores of illite-smectite mixed layers. Few organic-matter pores are observed. 2) New pores developing during thermal evolution are primarily organic matter pores and clay mineral pores, with diameters greater than 18 nm. Clay mineral pores with diameters of 18–50 nm are the principal contributors to porosity at temperatures between the low maturity stage and the oil-generation window, and organic matter pores with diameters of greater than 50 nm comprise the majority of pores generated between the gas-generation window and the high-/over-mature stages. 3) Porosity increases continuously with maturity, and the pore system varies at different maturity stages. Porosity evolution is controlled by illite content and organic matter abundance. Total pore volume correlates positively with illite content but negatively with organic matter abundance. These findings could provide guidance on shale oil evaluation in the Songliao Basin and assist in the ‘sweet-spotting’ of lacustrine shale systems across China.
Characterization of Physical Field and Flow Assurance Risk Analysis of Subsea Cage-Sleeve Throttling Valve
Authors: Jiang Donglei , Meng Wenbo , Huang Yi , Yu Yi , Zhou Youwei , Jiang Zhichen , Gao Yonghai
Published: December 2021

The subsea production system is presently widely adopted in deepwater oil and gas development. The throttling valve is the key piece of equipment of the subsea production system, controlling the safety of oil and gas production. There are many valves with serious throttling effect in the subsea X-tree, so the hydrate formation risk is relatively high. In this work, a 3D cage-sleeve throttling valve model was established by the numerical simulation method. The temperature and pressure field of the subsea throttling valve was accurately characterized under different prefilling pressure, throttling valve opening degree, and fluid production. During the well startup period, the temperature of the subsea pipeline is low. If the pressure difference between the two ends of the pipeline is large, the throttling effect is obvious, and low temperature will lead to hydrate formation and affect the choice of throttling valve material. Based on the analysis of simulation results, this study recommends that the prefilling pressure of the subsea pipe is 7–8 MPa, which can effectively reduce the influence of the throttling effect so that the downstream temperature can be kept above 0°C. At the same time, in regular production, a suitable choke size is opened to match the production, preventing the serious throttling effect from a small choke size. According to the API temperature rating table, the negative impact of local low temperature caused by the throttling effect on the temperature resistance of the pipe was considered, and the appropriate subsea X-tree manifold material was selected to ensure production safety. The hydrate phase equilibrium curve is used to estimate the hydrate formation risk under thermodynamic conditions. Hydrate inhibitors are injected to ensure downstream flow safety.
Migration and Distribution Characteristics of Proppant at the Corner of Horizontal Fracture Network in Coal Seam
Authors: Cheng Qingying , Li Haoze , Huang Bingxiang , Zhao Xinglong , Sun Zheng , Jiao Xuejie , Li Heng
Published: November 2021

A complex fracture network is composed of many similar structures. The migration law of proppant at each structure is the core and basic content of the migration law of proppant in complex fracture network, and there is little research. In this study, the EulerianEulerian method (TEM) is used to analyze the migration and distribution characteristics of solid–liquid two phases at the fracture corner according to different corner types of the fracture network. The results show that the migration characteristics of proppant in the corner area can be divided into the corner anomaly area, buffer area, and stability area; the influence of the turning angle on proppant migration is mainly concentrated at the corner and in the range of 4 times the fracture width after turning. The probability of sand plugging at the corner of the “Y → T” fracture is lower than that of “L → l”, higher than that of the “X → +” wing branch fracture, and lower than that of the main fracture. At the corner of the fracture network, after the solid flow turns, the proppant will form a high sand area on the side of the impact fracture surface, then rebound back to the fracture, form a sand-free area on the other side, and form a high-velocity core in the refraction interval. At the corner of the “L → l” fracture, there are one high sand area, one non-sand area, two low-velocity areas, and one high-velocity area; there are three low-velocity areas, two sand-free areas, and one high sand area at the corner of the “Y → T” fracture; at the corner of the “X → +” fracture, there is a high sand area and no sand-free area, and the flow velocity of the main fracture is much greater than that of the wing branch fracture.
Varied Relationship of Lipid and Lipoprotein Profiles to Liver Fat Content in Phenotypes of Metabolic Associated Fatty Liver Disease
Authors: Wu Tingfeng , Ye Junzhao , Shao Congxiang , Li Fuxi , Lin Yansong , Ma Qianqian , Wang Wei , Feng Shiting , Zhong Bihui
Published: December 2021

Background

Progressive overloads of intrahepatic triglycerides are related to metabolic dysregulation of multiple lipid and lipoprotein profiles, but whether similar dose effects are found in each subtype of metabolic associated fatty liver disease (MAFLD) remains unclear. We aimed to characterize the lipid profiles associated with liver fat content (LFC) in MAFLD patients who were overweight, lean/normal weight, or had diabetes.

Methods

We conducted a cross-sectional study enrolling 1,182 consecutive participants (144 non-MAFLD and 1,038 MAFLD) who underwent MRI proton density fat fraction measurement (MRI-PDFF) from 2011 to 2020. Lipid and apolipoprotein profiles, free fatty acid (FFA), liver and metabolism parameters, and anthropometric measurements were also assessed.

Results

MAFLD patients with type 2 diabetes or overweight/obesity had a higher proportion of abnormal lipid and lipoprotein profiles than those who were lean/normal weight. The degree of LFC had a positive correlation with total cholesterol, triglyceride, ApoB, and ApoE in patients with overweight/obesity and type 2 diabetes. In those with overweight/obesity, there were dose–response relationships between moderate-to-severe steatosis and total cholesterol, triglyceride, HDL-c, LDL-c, ApoB, ApoE, and Lp(a). A similar trend was observed for triglyceride in those with type 2 diabetes and for HDL-c in patients who were lean/normal weight (all p for trend <0.05). The combined model of relative lipid-related markers performed well in the prediction of moderate-to-severe steatosis (AUC: 0.762 for overweight/obesity; 0.742 for lean/normal weight).

Conclusion

LFC was associated with lipid profiles, including triglyceride, LDL-c, ApoB, ApoE, and FFA. These relationships were varied by the phenotype of MAFLD according to its diagnostic flow.
The Mutations and Clinical Variability in Maternally Inherited Diabetes and Deafness: An Analysis of 161 Patients
Authors: Yang Mengge , Xu Lusi , Xu Chunmei , Cui Yuying , Jiang Shan , Dong Jianjun , Liao Lin
Published: November 2021

Aims

To investigate the clinical features and mitochondrial mutations for maternally inherited diabetes and deafness.

Methods

PubMed, Embase, Medline, Web of Science, the China National Knowledge Infrastructure, and Wanfang were searched with the following search terms: “Maternally inherited diabetes and deafness” OR “MIDD” OR “Mitochondrial diabetes”. The mutations and clinical features were analyzed. Correlation between the heteroplasmy levels of the m.3243A>G mutation in the peripheral blood and age at the onset of diabetes was conducted by Spearman test. The significance level was set as p < 0.05. Statistical analysis was performed using the Statistical Package for the Social Sciences version 26 for Windows.

Results

Totally 161 patients with 21 different mitochondrial mutations were enrolled. The most common mutation was the m.3243A>G mutation in 136 cases. Of 142 patients, 120 (84.51%) had family histories of diabetes or hearing loss. Hearing loss presented in 85.71% of the patients with mitochondrial mutations. Central nervous system diseases were found in 29.19%, myopathy in 22.98%, oculopathy in 23.60%, cardiac disease in 23.60%, and nephropathy in 13.66% of the patients. Forty-two of 101 (41.58%) patients were underweight. A significant negative correlation was found between the heteroplasmy levels of the m.3243A>G mutation in the peripheral blood and age at the onset of diabetes.

Conclusions

The young onset of diabetes with low or normal BMI, maternal inheritance, and presence of impairments of multiple systems should prompt a genetic testing in order to differentiate MIDD from other types of diabetes earlier.
Perspective of the GEMSTONE Consortium on Current and Future Approaches to Functional Validation for Skeletal Genetic Disease Using Cellular, Molecular and Animal-Modeling Techniques
Authors: Rauner Martina , Foessl Ines , Formosa Melissa M. , Kague Erika , Prijatelj Vid , Lopez Nerea Alonso , Banerjee Bodhisattwa , Bergen Dylan , Busse Björn , Calado Ângelo , Douni Eleni , Gabet Yankel , Giralt Natalia García , Grinberg Daniel , Lovsin Nika M. , Solan Xavier Nogues , Ostanek Barbara , Pavlos Nathan J. , Rivadeneira Fernando , Soldatovic Ivan , van de Peppel Jeroen , van der Eerden Bram , van Hul Wim , Balcells Susanna , Marc Janja , Reppe Sjur , Søe Kent , Karasik David
Published: December 2021

The availability of large human datasets for genome-wide association studies (GWAS) and the advancement of sequencing technologies have boosted the identification of genetic variants in complex and rare diseases in the skeletal field. Yet, interpreting results from human association studies remains a challenge. To bridge the gap between genetic association and causality, a systematic functional investigation is necessary. Multiple unknowns exist for putative causal genes, including cellular localization of the molecular function. Intermediate traits (“endophenotypes”), e.g. molecular quantitative trait loci (molQTLs), are needed to identify mechanisms of underlying associations. Furthermore, index variants often reside in non-coding regions of the genome, therefore challenging for interpretation. Knowledge of non-coding variance (e.g. ncRNAs), repetitive sequences, and regulatory interactions between enhancers and their target genes is central for understanding causal genes in skeletal conditions. Animal models with deep skeletal phenotyping and cell culture models have already facilitated fine mapping of some association signals, elucidated gene mechanisms, and revealed disease-relevant biology. However, to accelerate research towards bridging the current gap between association and causality in skeletal diseases, alternative in vivo platforms need to be used and developed in parallel with the current -omics and traditional in vivo resources. Therefore, we argue that as a field we need to establish resource-sharing standards to collectively address complex research questions. These standards will promote data integration from various -omics technologies and functional dissection of human complex traits. In this mission statement, we review the current available resources and as a group propose a consensus to facilitate resource sharing using existing and future resources. Such coordination efforts will maximize the acquisition of knowledge from different approaches and thus reduce redundancy and duplication of resources. These measures will help to understand the pathogenesis of osteoporosis and other skeletal diseases towards defining new and more efficient therapeutic targets.
Diabetic Retinopathy and Insulin Insufficiency: Beta Cell Replacement as a Strategy to Prevent Blindness
Authors: Ipp Eli
Published: December 2021

Diabetic retinopathy (DR) is a potentially devastating complication of diabetes because it puts patients at risk of blindness. Diabetes is a common cause of blindness in the U.S. and worldwide and is dramatically increasing in global prevalence. Thus new approaches are needed to prevent this dreaded complication. There is extensive data that indicates beta cell secretory failure is a risk factor for DR, independent of its influence on glycemic control. This perspective article will provide evidence for insufficient endogenous insulin secretion as an important factor in the development of DR. The areas of evidence discussed are: (a) Presence of insulin receptors in the retina, (b) Clinical studies that show an association of beta cell insufficiency with DR, (c) Treatment with insulin in type 2 diabetes, a marker for endogenous insulin deficiency, is an independent risk factor for DR, (d) Recent clinical studies that link DR with an insulin deficient form of type 2 diabetes, and (e) Beta cell replacement studies that demonstrate endogenous insulin prevents progression of DR. The cumulative data drive our conclusion that beta cell replacement will have an important role in preventing DR and/or mitigating its severity in both type 1 diabetes and insulinopenic type 2 diabetes.
Brown Adipose Transplantation Improves Polycystic Ovary Syndrome-Involved Metabolome Remodeling
Authors: Yao Lihua , Wang Qin , Zhang Runjie , Wang Xingyun , Liu Yiwen , Di Fangfang , Song Liwen , Xu Siliang
Published: December 2021

Polycystic ovary syndrome (PCOS) is a complex reproductive, endocrine, and metabolic disorder in reproductive-age women. In order to explore the active metabolites of brown adipose tissue (BAT) transplantation in improving the reproductive and metabolic phenotypes in a PCOS rat model, the metabolites in the recipient’s BAT were explored using the liquid chromatography–mass spectrometry technique. In total, 9 upregulated and 13 downregulated metabolites were identified. They were roughly categorized into 12 distinct classes, mainly including glycerophosphoinositols, glycerophosphocholines, and sphingolipids. Ingenuity pathway analysis predicted that these differentially metabolites mainly target the PI3K/AKT, MAPK, and Wnt signaling pathways, which are closely associated with PCOS. Furthermore, one of these differential metabolites, sphingosine belonging to sphingolipids, was randomly selected for further experiments on a human granulosa-like tumor cell line (KGN). It significantly accelerated the apoptosis of KGN cells induced by dihydrotestosterone. Based on these findings, we speculated that metabolome changes are an important process for BAT transplantation in improving PCOS. It might be a novel therapeutic target for PCOS treatment.
The Role of Estrogen Receptor α in Response to Longitudinal Bone Growth in ob/ob Mice
Authors: Jin Lin-Yu , Guo Chen , Xu Shuai , Liu Hai-Ying , Li Xin-Feng
Published: December 2021

The absence of leptin results in contrasting growth pattern of appendicular and axial bone growth in ob/ob mice. Endochondral bone formation is an important procedure of growth plate determining the bone growth, where this procedure is also regulated by estrogen and its receptor (ER) signaling pathway. The present study is undertaken to explore the roles of ERs in regulating the different growth patterns in ob/ob mice. In this study, C57BL/6 female mice were used as wild-type (WT) mice; ob/ob mice and WT mice were age-matched fed, and bone length is analyzed by X-ray plain film at the 12 weeks old. We confirm that ob/ob mice have shorter femoral length and longer spine length than WT mice (p < 0.05). The contrasting expression patterns of chondrocyte proliferation proteins and hypertrophic marker proteins are also observed from the femur and spinal growth plate of ob/ob mice compared with WT mice (p < 0.01). Spearman’s analysis showed that body length (axial and appendicular length) is positively related to the expression level of ERα in growth plate. Three-week-old female ob/ob mice are randomized divided into three groups: 1) ob/ob + ctrl, 2) ob/ob + ERα antagonist (MPP), and 3) ob/ob + ERβ antagonist (PHTPP). Age-matched C57BL/6 mice were also divided into three groups, same as the groups of ob/ob mice. MPP and PHTPP were administered by intraperitoneal injection for 6 weeks. However, the results of X-ray and H&E staining demonstrate that leptin deficiency seems to disturb the regulating effects of ER antagonists on longitudinal bone growth. These findings suggested that region-specific expression of ERα might be associated with contrasting phenotypes of axial and appendicular bone growth in ob/ob mice. However, ER signaling on longitudinal bone growth was blunted by leptin deficiency in ob/ob mice, and the underlying association between ERs and leptin needs to be explored in future work.
An Update on the Relationship of SARS-CoV-2 and Male Reproduction
Authors: Guo Juncen , Sheng Kai , Wu Sixian , Chen Hanxiao , Xu Wenming
Published: November 2021

Since the outbreak of the COVID-19, up to now, infection cases have been continuously rising to over 200 million around the world. Male bias in morbidity and mortality has emerged in the COVID-19 pandemic. The infection of SARS-CoV-2 has been reported to cause the impairment of multiple organs that highly express the viral receptor angiotensin-converting enzyme 2 (ACE2), including lung, kidney, and testis. Adverse effects on the male reproductive system, such as infertility and sexual dysfunction, have been associated with COVID-19. This causes a rising concern among couples intending to have a conception or who need assisted reproduction. To date, a body of studies explored the impact of SARS-CoV-2 on male reproduction from different aspects. This review aims to provide a panoramic view to understand the effect of the virus on male reproduction and a new perspective of further research for reproductive clinicians and scientists.
Temperature-Dependent Crystallization Mechanisms of Methylammonium Lead Iodide Perovskite From Different Solvents
Authors: Shargaieva Oleksandra , Näsström Hampus , Li Jinzhao , Többens Daniel M. , Unger Eva L.
Published: November 2021

Hybrid perovskites are a novel type of semiconductors that show great potential for solution-processed optoelectronic devices. For all applications, the device performance is determined by the quality of the solution-processed perovskite thin films. During solution processing, the interaction of solvent with precursor molecules often leads to the formation of solvate intermediate phases that may diverge the crystallization pathway from simple solvent evaporation to a multi-step formation process. We here investigate the crystallization of methylammonium lead iodide (MAPbI3) from a range of commonly utilized solvents, namely dimethyl sulfoxide (DMSO), N,N-dimethylformamide (DMF), N-methylpyrrolidone (NMP), and gamma-butyrolactone (GBL) at different temperatures ranging from 40°C to >100°C by in-situ grazing-incidence wide-angle X-ray scattering (GIWAXS) measurements. For all solvents but GBL, we clearly observe the formation of solvate-intermediate phases at moderate processing temperatures. With increasing temperatures, an increasing fraction of the MAPbI3 perovskite phase is observed to form directly. From the temperature-dependence of the phase-formation and phase-decomposition rates, the activation energy to form the MAPbI3 perovskite phase from the solvate-phases are determined as a quantitative metric for the binding strength of the solvent within the solvate-intermediate phases and we observe a trend of DMSO > DMF > NMP > GBL. These results enable prediction of processing temperatures at which solvent molecules can be effectively removed.