bluuebunny/crossref_metadata_2025 huggingface dataset:
Chromatin Accessibility Predetermines Odontoblast Terminal Differentiation
Authors: Zhang Qian , Huang Zhen , Zuo Huanyan , Lin Yuxiu , Xiao Yao , Yan Yanan , Cui Yu , Lin Chujiao , Pei Fei , Chen Zhi , Liu Huan
Published: November 2021

Embryonic development and stem cell differentiation are orchestrated by changes in sequential binding of regulatory transcriptional factors to their motifs. These processes are invariably accompanied by the alternations in chromatin accessibility, conformation, and histone modification. Odontoblast lineage originates from cranial neural crest cells and is crucial in dentinogenesis. Our previous work revealed several transcription factors (TFs) that promote odontoblast differentiation. However, it remains elusive as to whether chromatin accessibility affects odontoblast terminal differentiation. Herein, integration of single-cell RNA-seq and bulk RNA-seq revealed that in vitro odontoblast differentiation using dental papilla cells at E18.5 was comparable to the crown odontoblast differentiation trajectory of OC (osteocalcin)-positive odontogenic lineage. Before in vitro odontoblast differentiation, ATAC-seq and H3K27Ac CUT and Tag experiments demonstrated high accessibility of chromatin regions adjacent to genes associated with odontogenic potential. However, following odontoblastic induction, regions near mineralization-related genes became accessible. Integration of RNA-seq and ATAC-seq results further revealed that the expression levels of these genes were correlated with the accessibility of nearby chromatin. Time-course ATAC-seq experiments further demonstrated that odontoblast terminal differentiation was correlated with the occupation of the basic region/leucine zipper motif (bZIP) TF family, whereby we validated the positive role of ATF5 in vitro. Collectively, this study reports a global mapping of open chromatin regulatory elements during dentinogenesis and illustrates how these regions are regulated via dynamic binding of different TF families, resulting in odontoblast terminal differentiation. The findings also shed light on understanding the genetic regulation of dentin regeneration using dental mesenchymal stem cells.
Function of Centriolar Satellites and Regulation by Post-Translational Modifications
Authors: Renaud Clotilde C. N. , Bidère Nicolas
Published: November 2021

Centriolar satellites are small membrane-less granules that gravitate around the centrosome. Recent advances in defining the satellite proteome and interactome have unveiled hundreds of new satellite components thus illustrating the complex nature of these particles. Although initially linked to the homeostasis of centrosome and the formation of primary cilia, these composite and highly dynamic structures appear to participate in additional cellular processes, such as proteostasis, autophagy, and cellular stress. In this review, we first outline the main features and many roles of centriolar satellites. We then discuss how post-translational modifications, such as phosphorylation and ubiquitination, shape their composition and functions. This is of particular interest as interfering with these processes may provide ways to manipulate these structures.
Facile Synthesis of Pd-Ir Nanocubes for Biosensing
Authors: Li Jiuxing , Li Yingfu
Published: November 2021

Displaying extremely high peroxidase-like activity and uniform cubic structure enclosed by (100) facets, Pd-Ir nanocubes are an attractive nanomaterial for bioanalysis. However, there exists a great challenge to deposit atomic layers of Ir on the surface of Pd nanocubes due to the relatively low energy barrier of homogeneous nucleation of Ir atoms compared to heterogeneous nucleation. Here, a simple and surfactant-free approach is presented to synthesize Pd-Ir nanocubes with atomic Ir shell thickness in an aqueous solution at room temperature. Biomolecules such as antibodies and nucleic acids have free access to the surface of Pd-Ir nanocubes. Applications of Pd-Ir nanocubes in immunoassays and aptamer-based biosensors are realized, exploiting the excellent peroxidase activity and fluorescence quenching ability of Pd-Ir nanocubes. This work makes a significant step forward towards the practical utility of Pd-Ir nanocubes in bioanalysis.
Basicity as a Thermodynamic Descriptor of Carbanions Reactivity with Carbon Dioxide: Application to the Carboxylation of α,β-Unsaturated Ketones
Authors: Franceschi Pietro , Nicoletti Catia , Bonetto Ruggero , Bonchio Marcella , Natali Mirco , Dell’Amico Luca , Sartorel Andrea
Published: November 2021

The utilization of carbon dioxide as a raw material represents nowadays an appealing strategy in the renewable energy, organic synthesis, and green chemistry fields. Besides reduction strategies, carbon dioxide can be exploited as a single-carbon-atom building block through its fixation into organic scaffolds with the formation of new C-C bonds (carboxylation processes). In this case, activation of the organic substrate is commonly required, upon formation of a carbanion C−, being sufficiently reactive toward the addition of CO2. However, the prediction of the reactivity of C− with CO2 is often problematic with the process being possibly associated with unfavorable thermodynamics. In this contribution, we present a thermodynamic analysis combined with density functional theory calculations on 50 organic molecules enabling the achievement of a linear correlation of the standard free energy (ΔG0) of the carboxylation reaction with the basicity of the carbanion C−, expressed as the pKa of the CH/C− couple. The analysis identifies a threshold pKa of ca 36 (in CH3CN) for the CH/C− couple, above which the ΔG0 of the carboxylation reaction is negative and indicative of a favorable process. We then apply the model to a real case involving electrochemical carboxylation of flavone and chalcone as model compounds of α,β-unsaturated ketones. Carboxylation occurs in the β-position from the doubly reduced dianion intermediates of flavone and chalcone (calculated ΔG0 of carboxylation in β = −12.8 and −20.0 Kcalmol-1 for flavone and chalcone, respectively, associated with pKa values for the conjugate acids of 50.6 and 51.8, respectively). Conversely, the one-electron reduced radical anions are not reactive toward carboxylation (ΔG0 > +20 Kcalmol-1 for both substrates, in either α or β position, consistent with pKa of the conjugate acids < 18.5). For all the possible intermediates, the plot of calculated ΔG0 of carboxylation vs. pKa is consistent with the linear correlation model developed. The application of the ΔG0 vs. pKa correlation is finally discussed for alternative reaction mechanisms and for carboxylation of other C=C and C=O double bonds. These results offer a new mechanistic tool for the interpretation of the reactivity of CO2 with organic intermediates.
Studies on Growth Characteristics and Cross-Neutralization of Wild-Type and Delta SARS-CoV-2 From Hisar (India)
Authors: Khandelwal Nitin , Chander Yogesh , Kumar Ram , Nagori Himanshu , Verma Assim , Mittal Priyasi , T Riyesh , Kamboj Sameer , Verma Sukhbir Singh , Khatreja Subhash , Pal Yash , Gulati Baldev R. , Tripathi Bhupendra N. , Barua Sanjay , Kumar Naveen
Published: November 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly evolved to generate several antigenic variants. These variants have raised concerns whether pre-existing immunity to vaccination or prior infection would be able to protect against the newly emerging SARS-CoV-2 variants or not. We isolated SARS-CoV-2 from the coronavirus disease 2019 (COVID-19)-confirmed patients in the beginning of the first (April/May 2020) and second (April/May 2021) waves of COVID-19 in India (Hisar, Haryana). Upon complete nucleotide sequencing, the viruses were found to be genetically related with wild-type (WT) and Delta variants of SARS-CoV-2, respectively. The Delta variant of SARS-CoV-2 produced a rapid cytopathic effect (24–36 h as compared to 48–72 h in WT) and had bigger plaque size but a shorter life cycle (~6 h as compared to the ~8 h in WT). Furthermore, the Delta variant achieved peak viral titers within 24 h as compared to the 48 h in WT. These evidence suggested that the Delta variant replicates significantly faster than the WT SARS-CoV-2. The virus neutralization experiments indicated that antibodies elicited by vaccination are more efficacious in neutralizing the WT virus but significantly less potent against the Delta variant. Our findings have implications in devising suitable vaccination, diagnostic and therapeutic strategies, besides providing insights into understanding virus replication and transmission.
A Need for Context-Based Conservation: Incorporating Local Knowledge to Mitigate Livestock Predation by Large Carnivores
Authors: Bijoor Ajay , Khanyari Munib , Dorjay Rigzen , Lobzang Sherab , Suryawanshi Kulbhushansingh
Published: November 2021

Mitigating livestock predation by carnivores is crucial to ensure carnivore conservation and facilitate human-carnivore coexistence. Mitigation measures proposed by conservation agencies, however, are often technocratic and perceived as being an external imposition on the local community. Herders affected by the depredation may have the knowledge to design locally relevant solutions, but they might lack financial and technical support to implement these effectively. Their inability to act can result in the communities being viewed as antagonistic rather than a part of the solution. We present a case study on co-development of a conservation intervention by a traditional pastoral community together with a conservation NGO, to mitigate livestock depredation inside night-time corrals in Ladakh, India. Between January and June 2020, livestock corrals in Sumdoo TR village were attacked 10 times by carnivores such as snow leopards and wolves, killing over 100 sheep, goat, yak, and horses and causing loses of over 10,400 USD. Local people were agitated, and there were strong demands for capture or removal of the carnivores from the area. We operationalized the PARTNERS (Presence, Aptness, Respect, Transparency, Negotiation, Empathy, Responsiveness, and Strategic Support) principles framework for community-based conservation to help the village effectively implement an intervention based on a novel predator-proof corral design conceptualized by the community. We demonstrate that empowering the community to design and implement a conservation intervention helped them take ownership of the effort, improve trust with conservation agencies, and hence likely to be a long-term solution to conservation conflicts in the region. Our approach of using the PARTNERS principles has relevance for conservation agencies who are trying to implement interventions, particularly those geared toward reducing livestock depredation by carnivores. Our approach further helps communities to view themselves as part of the solution and not the problem.
Effects of Metoprolol on Periprocedural Myocardial Infarction After Percutaneous Coronary Intervention (Type 4a MI): An Inverse Probability of Treatment Weighting Analysis
Authors: Li Duanbin , Li Ya , Lin Maoning , Zhang Wenjuan , Fu Guosheng , Chen Zhaoyang , Jin Chongying , Zhang Wenbin
Published: November 2021

Background: Metoprolol is the most used cardiac selective β-blocker and has been recommended as a mainstay drug in the management of acute myocardial infarction (AMI). However, the evidence supporting this regimen in periprocedural myocardial infarction (PMI) is limited.

Methods: This study identified 860 individuals who suffered PMI following percutaneous coronary intervention (PCI) procedure and median followed up for 3.2 years. Subjects were dichotomized according to whether they received chronic oral sustained-release metoprolol succinate following PMI. After inverse probability of treatment weighting (IPTW) adjustment, logistic regression analysis, Kaplan-Meier curve, and Cox regression analysis were performed to estimate the effects of metoprolol on major adverse cardiovascular events (MACEs) which composed of cardiac death, myocardial infarction (MI), stroke, and revascularization. Moreover, an exploratory analysis was performed according to hypertension, cardiac troponin I (cTnI) elevation, and cardiac function. A double robust adjustment was used for sensitivity analysis.

Results: Among enrolled PMI subjects, 456 (53%) patients received metoprolol treatment and 404 (47%) patients received observation. After IPTW adjustment, receiving metoprolol was found to reduce the subsequent 3-year risk of MACEs by nearly 7.1% [15 vs. 22.1%, absolute risk difference (ARD) = 0.07, number needed to treat (NNT) = 14, relative risk (RR) = 0.682]. In IPTW-adjusted Cox regression analyses, receiving metoprolol was related to a reduced risk of MACEs (hazard ratio [HR] = 0.588, 95%CI [0.385–0.898], P = 0.014) and revascularization (HR = 0.538, 95%CI [0.326–0.89], P = 0.016). Additionally, IPTW-adjusted logistic regression analysis showed that receiving metoprolol reduced the risk of MI at the third year (odds ratio [OR] = 0.972, 95% CI [0.948–997], P = 0.029). Exploratory analysis showed that the protective effect of metoprolol was more pronounced in subgroups of hypertension and cTnI elevation ≥1,000%, and was remained in patients without cardiac dysfunction. The benefits above were consistent when double robust adjustments were performed.

Conclusion: In the real-world setting, receiving metoprolol treatment following PCI-related PMI has decreased the subsequent risk of MACEs, particularly the risk of recurrent MI and revascularization.
Incidence- and In-hospital Mortality-Related Risk Factors of Acute Kidney Injury Requiring Continuous Renal Replacement Therapy in Patients Undergoing Surgery for Acute Type a Aortic Dissection
Authors: Chen Xuelian , Zhou Jiaojiao , Fang Miao , Yang Jia , Wang Xin , Wang Siwen , Li Linji , Zhu Tao , Ji Ling , Yang Lichuan
Published: November 2021

Background: Few studies on the risk factors for postoperative continuous renal replacement therapy (CRRT) in a homogeneous population of patients with acute type A aortic dissection (AAAD). This retrospective analysis aimed to investigate the risk factors for CRRT and in-hospital mortality in the patients undergoing AAAD surgery and to discuss the perioperative comorbidities and short-term outcomes.

Methods: The study collected electronic medical records and laboratory data from 432 patients undergoing surgery for AAAD between March 2009 and June 2021. All the patients were divided into CRRT and non-CRRT groups; those in the CRRT group were divided into the survivor and non-survivor groups. The univariable and multivariable analyses were used to identify the independent risk factors for CRRT and in-hospital mortality.

Results: The proportion of requiring CRRT and in-hospital mortality in the patients with CRRT was 14.6 and 46.0%, respectively. Baseline serum creatinine (SCr) [odds ratio (OR), 1.006], cystatin C (OR, 1.438), lung infection (OR, 2.292), second thoracotomy (OR, 5.185), diabetes mellitus (OR, 6.868), AKI stage 2–3 (OR, 22.901) were the independent risk factors for receiving CRRT. In-hospital mortality in the CRRT group (46%) was 4.6 times higher than in the non-CRRT group (10%). In the non-survivor (n = 29) and survivor (n = 34) groups, New York Heart Association (NYHA) class III-IV (OR, 10.272, P = 0.019), lactic acidosis (OR, 10.224, P = 0.019) were the independent risk factors for in-hospital mortality in patients receiving CRRT.

Conclusion: There was a high rate of CRRT requirement and high in-hospital mortality after AAAD surgery. The risk factors for CRRT and in-hospital mortality in the patients undergoing AAAD surgery were determined to help identify the high-risk patients and make appropriate clinical decisions. Further randomized controlled studies are urgently needed to establish the risk factors for CRRT and in-hospital mortality.
Association Between Circulating Proprotein Convertase Subtilisin/Kexin Type 9 Concentrations and Cardiovascular Events in Cardiovascular Disease: A Systemic Review and Meta-Analysis
Authors: Liu Jiahui , Fan Fangfang , Luo Xingyu , Ji Wenjun , Liu Yaokun , Zhang Yan , Zheng Bo
Published: November 2021

Background: A large amount of evidence suggests that proprotein convertase subtilisin/Kexin type 9 (PCSK9) inhibitors have clinical benefits in patients with cardiovascular disease (CVD). However, whether PCSK9 concentrations predict future cardiovascular (CV) events remains unclear.

Methods: We conducted a meta-analysis to investigate the ability of PCSK9 concentrations to predict future CV events in patients with established CVD. A comprehensive search of electronic databases was conducted in June 2021. We included relative risk (RR) estimates with 95% CI or events of interest.

Results: Eleven cohort studies including 8,471 patients with CVD were enrolled. The pooled RR of CV events for the increase in the circulating baseline PCSK9 concentrations by 1 SD showed a positive association in a random-effect model (RR 1.226, 95% CI: 1.055–1.423, P = 0.008). Similarly, the risk of the total CV events increased by 52% in the patients in the highest tertile compared with those in the lowest tertile of circulating PCSK9 concentrations (RR 1.523, 95% CI: 1.098–2.112, P = 0.012). The association between PCSK9 and CV events was stronger in stable patients with CVD, patients treated with statins, and Asian patients.

Conclusions: High PCSK9 concentrations are significantly related to the increased risk of future CV events. These results enrich the knowledge of PCSK9 function and suggest the further possible clinical role of PCSK9 inhibitors.
Six Months of Inspiratory Muscle Training to Lower Blood Pressure and Improve Endothelial Function in Middle-Aged and Older Adults With Above-Normal Blood Pressure and Obstructive Sleep Apnea: Protocol for the CHART Clinical Trial
Authors: Tavoian Dallin , Ramos-Barrera Lupita E. , Craighead Daniel H. , Seals Douglas R. , Bedrick Edward J. , Alpert Joseph S. , Mashaqi Saif , Bailey E. Fiona
Published: November 2021

Background: Cardiovascular disease is a major global health concern and prevalence is high in adults with obstructive sleep apnea (OSA). Lowering blood pressure (BP) can greatly reduce cardiovascular disease risk and physical activity is routinely prescribed to achieve this goal. Unfortunately, many adults with OSA suffer from fatigue, daytime sleepiness, and exercise intolerance—due to poor sleep quality and nocturnal hypoxemia—and have difficulty initiating and maintaining an exercise program. High-resistance inspiratory muscle strength training (IMST) is a simple, time-efficient breathing exercise consistently reported to reduce BP in small, selective groups of both healthy and at-risk adults. Herein we present the study protocol for a randomized clinical trial to determine the long-term efficacy of IMST performed regularly for 24 weeks in middle-aged and older adults with OSA. The primary outcome is casual systolic BP. Secondary outcomes are 24-h systolic BP and circulating plasma norepinephrine concentration. Other outcomes include vascular endothelial function (endothelial-dependent and -independent dilation), aortic stiffness, casual and 24-h diastolic BP, and the influence of circulating factors on endothelial cell nitric oxide and reactive oxygen species production. Overall, this trial will establish efficacy of high-resistance IMST for lowering BP and improving cardiovascular health in middle-aged and older adults with OSA.

Methods: This is a single-site, double-blind, randomized clinical trial. A minimum of 92 and maximum of 122 male and female adults aged 50–80 years with OSA and above-normal BP will be enrolled. After completion of baseline assessments, subjects will be randomized in a 1:1 ratio to participate in either high-resistance or sham (low-resistance) control IMST, performed at home, 5 min/day, 5 days/week, for 24 weeks. Repeat assessments will be taken after the 24-week intervention, and after 4 and 12 weeks of free living.

Discussion: This study is designed to assess the effects of 24 weeks of IMST on BP and vascular function. The results will characterize the extent to which IMST can reduce BP when performed over longer periods (i.e., 6 months) than have been assessed previously. Additionally, this study will help to determine underlying mechanisms driving IMST-induced BP reductions that have been reported previously.

Clinical Trial Registration: This trial is registered with ClinicalTrials.gov (Registration Number: NCT04932447; Date of registration June 21, 2021).
Coagulation in Lymphatic System
Authors: Zhang Wendi , Li Jiang , Liang Jiangjiu , Qi Xiumei , Tian Jinghui , Liu Ju
Published: November 2021

The lymphatic system maintains homeostasis of the internal environment between the cells in tissues and the blood circulation. The coagulation state of lymph is determined by conditions of coagulation factors and lymphatic vessels. Internal obliteration, external compression or abnormally increased lymphatic pressure may predispose to localized lymphatic coagulation. In physiological conditions, an imbalance of antithrombin and thrombokinase reduces lymphatic thrombosis. However, the release of factor X by lymphatic endothelium injury may trigger coagulation casacade, causing blockage of lymphatic vessels and lymphedema. Heterogeneity of lymphatic vessels in various tissues may lead to distinct levels and patterns of coagulation in specific lymphatic vessels. The quantitative and qualitative measurement of clotting characteristic reveals longer time for clotting to occur in the lymph than in the blood. Cancer, infections, amyloidosis and lymph node dissection may trigger thrombosis in the lymphatic vessels. In contrast to venous or arterial thrombosis, lymphatic thrombosis has rarely been reported, and its actual prevalence is likely underestimated. In this review, we summarize the mechanisms of coagulation in lymphatic system, and discuss the lymphatic thrombosis-related diseases.
Association Between Long-Term Visit-to-Visit Hemoglobin A1c and Cardiovascular Risk in Type 2 Diabetes: The ACCORD Trial
Authors: Huang Dan , Huang Yong-Quan , Zhang Qun-Ying , Cui Yan , Mu Tian-Yi , Huang Yin
Published: November 2021

Background: To explore the association between visit-to-visit variability of glycated hemoglobin (HbA1c) and cardiovascular outcomes in the patients with type 2 diabetes mellitus (T2DM) of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study.

Methods: We conducted a post-hoc analysis on the ACCORD population including 9,544 participants with T2DM. Visit-to-visit variability of HbA1c was defined as the individual SD, coefficient of variation (CV), and variability independent of the mean (VIM) across HbA1c measurements. The clinical measurements included primary outcome [the first occurrence of non-fatal myocardial infarction (MI), non-fatal stroke or cardiovascular death], total mortality, cardiovascular death, non-fatal MI event, non-fatal stroke, total stroke, heart failure, macrovascular events, and major coronary events (CHD).

Results: Over a median follow-up of 4.85 years, 594 and 268 participants experienced all-cause mortality and cardiovascular mortality, respectively. After adjusting for baseline HbA1c levels and confounding factors, the adjusted hazard ratio (HR) comparing patients in the highest vs. the lowest quartile CV of HbA1c variability was 1.61 (95% CI 1.29–2.00) for the primary outcome. Similar trends for secondary outcome were also observed. There was no association between HbA1c fluctuation and non-fatal stroke. Noticeably, there was 66% greater risk for the all-cause mortality among patients in the highest vs. the lowest quartile (HR 1.66, 95% CI 1.27–2.17).

Conclusions: Greater variability of HbA1c is associated with higher risk for cardiovascular complications and all-cause death in T2DM. Our study stresses the significance of well-controlled glycemic levels for improving cardiovascular outcomes. Further randomized clinical trials are required to confirm these findings.
Clinical Impact of Single and Dual Antiplatelet Therapy Beyond 12 Months on Ischemic Risk in Patients With Acute Myocardial Infarction
Authors: Roh Ji Woong , Bae SungA , Kim Yongcheol , Son Nak-Hoon , Cho Deok-Kyu , Kim Jung-Sun , Kim Byeong-Keuk , Choi Donghoon , Hong Myeong-Ki , Jeong Myung Ho , Jang Yangsoo ,   the KAMIR-NIH Investigators
Published: November 2021

Background: There is ongoing debate regarding the optimal antiplatelet strategy beyond 12 months in patients with acute myocardial infarction (AMI) who undergo successful percutaneous coronary intervention (PCI). This study therefore aimed to investigate the clinical outcomes of single (SAPT) vs. dual antiplatelet therapy (DAPT) beyond 12 months in patients with stable AMI and second-generation drug-eluting stent (DES) implantation.

Methods: Of 13,104 patients from the Korea Acute Myocardial Infarction Registry-National Institutes of Health database, we selected 4,604 patients who underwent PCI with second-generation DES and exhibited no adverse clinical events within 12 months; they were classified into SAPT (aspirin or clopidogrel) or DAPT (aspirin and clopidogrel) groups. The primary endpoints were major adverse cardiac and cerebrovascular events (MACCE), including the composite of all-cause death, myocardial infarction (MI), and stroke between 12 and 36 months.

Results: The SAPT group (n = 1,862) was associated with a significantly lower risk of MACCE between 12 and 36 months [4.2 vs. 8.5%, hazard ratio (HR): 0.47, 95% confidence interval (CI): 0.37–0.61; p < 0.001] than the DAPT group (n = 2,742). The results were consistent after adjusting for confounders through multivariable and propensity score matching analysis. Moreover, in patients with complex features (defined as an unprotected left main PCI, implanted stent length of ≥38 mm, multivessel PCI, or ≥3 stents per patients), the SAPT group (n = 678) also demonstrated a significantly lower risk of MACCE between 12 and 36 months (4.9 vs. 9.9%, HR: 0.46, CI: 0.31–0.68, p < 0.001) than the DAPT group (n = 1,167).

Conclusions: In patients with AMI who underwent successful PCI with second-generation DES and exhibited no adverse clinical events within 12 months, the use of SAPT was associated with a significantly lower MACCE between 12 and 36 months compared with the use of DAPT.
Alternative Pathways for Hearing Care May Address Disparities in Access
Authors: Willink Amber , Assi Lama , Nieman Carrie , McMahon Catherine , Lin Frank R. , Reed Nicholas S.
Published: November 2021

Background/Objectives: Low-uptake of hearing aids among older adults has long dogged the hearing care system in the U.S. and other countries. The introduction of over-the-counter hearing aids is set to disrupt the predominantly high-cost, specialty clinic-based delivery model of hearing care with the hope of increasing accessibility and affordability of hearing care. However, the current model of hearing care delivery may not be reaching everyone with hearing loss who have yet to use hearing aids. In this study, we examine the group of people who do not use hearing aids and describe their characteristics and health care utilization patterns. We also consider what other healthcare pathways may be utilized to increase access to hearing treatment.

Design: Cross-sectional, the 2017 Medicare Current Beneficiary Survey.

Setting: Non-institutionalized adults enrolled in Medicare, the U.S. public health insurance program for older adults (65 years and older) and those with qualifying medical conditions and disabilities.

Participants: A nationally representative sample of 7,361 Medicare beneficiaries with self-reported trouble hearing and/or hearing aid use.

Measurements: Survey-weighted proportions described the population characteristics and health care utilization of those with hearing loss by hearing aid use, and the characteristics of those with untreated hearing loss by health care service type utilized.

Results: Women, racial/ethnic minorities, and low-income Medicare beneficiaries with self-reported hearing trouble were less likely to report using hearing aids than their peers. Among those who do not use hearing aids, the most commonly used health care services were obtaining prescription drugs (64%) and seeing a medical provider (50%). Only 20% did not access either service in the past year. These individuals were more likely to be young and to have higher educational attainment and income.

Conclusion: Alternative models of care delivered through pharmacies and general medical practices may facilitate access to currently underserved populations as they are particularly high touch-points for Medicare beneficiaries with untreated hearing trouble. As care needs will vary across a spectrum of hearing loss, alternative models of hearing care should look to complement not substitute for existing access pathways to hearing care.
Experimental Study on Gangue Backfilling Materials Improved by Soda Residue and Field Measurement of Surface Subsidence
Authors: Yin Wei , Zhang Kun , Ouyang Shenyang , Bai Xiaomin , Sun Wenjie , Zhao Jingru
Published: November 2021

In coal mining, the problems of massive discharge of solid waste, environmental pollution, and surface subsidence disaster are urgent to be solved. Based on this engineering background, the feasibility of using solid waste soda residue to improve gangue cemented backfilling material was discussed, and the surface subsidence of the test working face was measured in this study. Besides, the influence of soda residue on the performance of gangue cemented backfilling materials was analyzed through laboratory tests. The experimental results show that 1) as the content of soda residue increases within the range of 0–12%, the slump of the soda residue gangue backfilling material (SRGBM) slurry gradually increases, and the bleeding rate increases. The early strength and later strength of SRGBM increase first and then decrease with the increase in soda residue content. 2) The optimal ratio of the soda residue cemented backfilling material is soda residue: fly ash: lime: cement: gangue = 6%: 34%: 10%: 2.5%: 47.5%. Compared with the reference group, the slump of the material is increased by 12.7%, the bleeding rate is only 3.8%, and the early strength and later strength are increased by 449 and 187%, respectively. 3) The addition of soda residue promotes the hydration reaction of the slurry system of soda residue cemented materials. The coexistence of C-S-H gel and N-A-S-H gel reduces the connectivity of pores and improves the strength of the material. 4) The maximum surface subsidence of the test working face is only 245 mm, and the surface subsidence control effect is good. Therefore, the preparation of SRGBM with soda residue can achieve energy saving and emission reduction, with significant technical, economic, and social benefits, and has good promotion and application value.
Reverse Time Migration of Vertical Cable Seismic Data to Image Hydrate-Bearing Sediments With High Resolution
Authors: Wang Linfei , Liu Huaishan , Wang Zhong , Zhang Jin , Xing Lei , Yin Yanxin
Published: November 2021

Marine vertical cable seismic (VCS) is a promising survey technique for submarine complex structure imaging and reservoir monitoring, which uses vertical arrays of hydrophones deployed near the seafloor to record seismic wavefields in a quiet environment. Recently, we developed a new type of distributed VCS system for exploration and development of natural gas hydrates preserved in shallow sediments under the seafloor. Using this system and air-gun sources, we accomplished a 3D VCS yield data acquisition for gas hydrates exploration in the Shenhu area, South China Sea. In view of the characteristics of VCS geometry, we implement reverse time migration (RTM) on a common receiver gather to obtain high-resolution images of marine sediments. Due to the unique acquisition method, it is asymmetrical for the reflection path between the sources and the receivers in the VCS survey. Therefore, we apply accurate velocity analysis to common scatter point (CSP) gathers generated from common receiver gathers instead of the conventional velocity analysis based on common depth point gathers. RTM with this reliable velocity model results in high-resolution images of submarine hydrate-bearing sediments in deep water conditions. The RTM imaging section clearly shows the bottom simulating reflector (BSR) and also the reflection characteristics of the hydrate-bearing sediments filled with consolidated hydrates. Moreover, its resolution is relative to that of acoustic logging curves from the nearby borehole, and this imaging section is well consistent with the synthetic seismogram trace generated by the logging data. All these results reveal that VCS is a great potential technology for exploration and production of marine natural gas hydrates.
Aerodynamic Characteristics Over Fine-Grained Gravel Surfaces in a Wind Tunnel
Authors: Liu Jiaqi , Kimura Reiji , Wu Jing
Published: November 2021

Gravels can protect soil from wind erosion, however, there is little known about the effects of fine-grained gravel on aerodynamic characteristics of the near-surface airflow. Drag coefficient, wind-speed gradient, and turbulent transfer coefficient over different coverages of gravel surfaces were investigated in a compact boundary-layer wind tunnel. The drag coefficient of the fine-grained gravel surface reached the maximum value at 15% coverage and then tended to stabilize at gravel coverage 20% and greater. At a height of 4 cm, near-surface airflow on gravel surfaces can be divided clearly into upper and lower sublayers, defined as the inertial and roughness sublayers, respectively. The coefficient of variation of wind speed over gravel surfaces in the roughness sublayer was 8.6 times that in the inertial sublayer, indicating a greater effect of gravel coverage on wind-speed fluctuations in the lower layer. At a height of 4 cm, wind-speed fluctuations under the observed wind speeds were independent of changes in gravel coverage. In addition, an energy-exchange region, where sand particles can absorb more energy from the surrounding airflow, was found between the roughness and inertial sublayers, enhancing the erosional state of wind-blown sand. This finding can be applied to evaluate the aerodynamic stability of the gravel surface in the Gobi Desert and provide a theoretical basis for elucidation of the vertical distributions of wind-blown sand flux.
Moisture Transport and Sources of the Extreme Precipitation Over Northern and Southern Xinjiang in the Summer Half-Year During 1979–2018
Authors: Hu Qin , Zhao Yong , Huang Anning , Ma Pan , Ming Jing
Published: November 2021

Based on the output data from the Lagrangian flexible particle dispersion model (FLEXPART), we analyze the pathways of moisture to identify the moisture source areas for extreme precipitation in the summer half-year (April–September) over northern and southern Xinjiang, respectively. For both northern and southern Xinjiang, the local evaporation plays a decisive role for extreme precipitation in the summer half-year, of which contribution ratio accounts for 24.5% to northern Xinjiang and 30.2% to southern Xinjiang of all identified source areas. In addition, central Asia and northwestern Asia are the major moisture source areas as well and contribute similarly to extreme precipitation relative to local evaporation. For northern Xinjiang, central Asia surpasses northwestern Asia, and each of them contributes 24.1 and 18.8%, whereas northwestern Asia is somewhat more crucial than central Asia for southern Xinjiang, accounting 22.1 and 19.1%, respectively. Note that the three top-ranked moisture source areas make up a large proportion of total sources. Regarding the remaining source areas that also provide moisture, the contributions are entirely different for southern and northern Xinjiang. Originating from the North Atlantic Ocean, Europe, and the Mediterranean Sea, some water vapor enters northern Xinjiang and converge to precipitate, while this process is barely detectable for extreme precipitation over southern Xinjiang, which is affected by the westerly flow. On the contrary, the Arabian Sea, the Arabian Peninsula, and the Indian Peninsula contribute, even though slightly, to extreme precipitation over southern Xinjiang, which indicates that the meridional transport pathways from the Arabian Sea can carry moisture to this inland region.
Oxidized Phospholipids in Control of Endothelial Barrier Function: Mechanisms and Implication in Lung Injury
Authors: Karki Pratap , Birukov Konstantin G.
Published: November 2021

Earlier studies investigating the pathogenesis of chronic vascular inflammation associated with atherosclerosis described pro-inflammatory and vascular barrier disruptive effects of lipid oxidation products accumulated in the sites of vascular lesion and atherosclerotic plaque. However, accumulating evidence including studies from our group suggests potent barrier protective and anti-inflammatory properties of certain oxidized phospholipids (OxPLs) in the lung vascular endothelium. Among these OxPLs, oxidized 1-palmitoyl-2-arachdonyl-sn-glycero-3-phosphocholine (OxPAPC) causes sustained enhancement of lung endothelial cell (EC) basal barrier properties and protects against vascular permeability induced by a wide variety of agonists ranging from bacterial pathogens and their cell wall components, endotoxins, thrombin, mechanical insults, and inflammatory cytokines. On the other hand, truncated OxPLs cause acute endothelial barrier disruption and potentiate inflammation. It appears that multiple signaling mechanisms triggering cytoskeletal remodeling are involved in OxPLs-mediated regulation of EC barrier. The promising vascular barrier protective and anti-inflammatory properties exhibited by OxPAPC and its particular components that have been established in the cellular and animal models of sepsis and acute lung injury has prompted consideration of OxPAPC as a prototype therapeutic molecule. In this review, we will summarize signaling and cytoskeletal mechanisms involved in OxPLs-mediated damage, rescue, and restoration of endothelial barrier in various pathophysiological settings and discuss a future potential of OxPAPC in treating lung disorders associated with endothelial barrier dysfunction.
Techno-Economic Analysis of a Flexible Process Concept for the Production of Transport Fuels and Heat from Biomass and Renewable Electricity
Authors: Habermeyer Felix , Kurkela Esa , Maier Simon , Dietrich Ralph-Uwe
Published: November 2021

Different processes have been proposed to meet the global need for renewable fuel. The Biomass to Liquid process (BtL) converts biomass via the Fischer-Tropsch route to hydrocarbon chains that can be refined to transport fuel. With the addition of electrolytic hydrogen to the Power and Biomass to Liquid process (PBtL), the carbon efficiency can be increased relative to the BtL process. It was shown in previous studies that the PBtL concept has an economic edge over BtL when cheap electricity is available to maximize the fuel yield. In this study, a techno-economic analysis is conducted for a hybrid process concept which can switch operation modes from electrolysis enhanced to only biomass conversion. In case studies the effect of the Fischer-Tropsch conversion, H2/CO ratio of the Fischer-Tropsch feed and the biomass feed rate in the electrolysis enhanced mode are analyzed. Every process configuration is modeled based on experimentally validated unit models from literature in the commercial software Aspen Plus and analyzed using DLR’s software tool TEPET. For a 200 MWth biomass input plant, production costs of 1.08 €2019/L for the hybrid concept with a carbon efficiency of 53.3% compared to 0.66 €2019/L for BtL with 35.4% and 1 €2019/L for PBtL with 61.1% were found based on the Finnish day-ahead market for the base case. The net production cost for the hybrid concept can be decreased by 0.07 €2019/L when a Fischer-Tropsch H2/CO ratio of 1.6 instead of 2.05 is used.
Electrical DebtRank Algorithm–Based Identification of Vulnerable Transmission Lines in Power Systems
Authors: Li Lijuan , Zeng Yiwei , Chen Jie , Li Yue , Liu Hai , Ding Gangwei
Published: November 2021

With the increase of complexity of the power system structure and operation mode, the risk of large-scale power outage accidents rises, which urgently need an accuracy algorithm for identifying vulnerabilities and mitigating risks. Aiming at this, the improved DebtRank (DR) algorithm is modified to adapt to the property of the power systems. The overloading state of the transmission lines plays a notable role of stable operation of the power systems. An electrical DR algorithm is proposed to incorporate the overloading state to the identification of vulnerable lines in the power systems in this article. First, a dual model of power system topology is established, the nodes of which represent the lines in the power systems. Then, besides the normal state and failure state having been considered, the definition of the overloading state is also added, and the line load and network topology are considered in the electrical DR algorithm to identify vulnerable lines. Finally, the correctness and reasonability of the vulnerable lines of the power systems identified by the electrical DR algorithm are proved by the comparative analysis of cascade failure simulation, showing its better advantages in vulnerability assessment of power systems.
Analysis of Drought and Flood Disasters During 0–1950 AD in the Hexi Corridor, China, Based on Historical Documents
Authors: Tang Xia , Feng Qi
Published: November 2021

It is important to analyze the characteristics of drought and flood change in an arid area over a long timescale for the evolution of the environment. Historical documents were used to reconstruct a drought and flood grade series for the Hexi Corridor from 0 to 1950 AD. The moving average and wavelet transform processing methods were used to determine the temporal evolution characteristics of droughts and floods, as well as the corresponding relationships with climate change and human activities in the Hexi Corridor after 1000 AD. The results showed the occurrence of eight drought phases (370–410 AD, 790–870 AD, 1050–1150 AD, 1260–1340 AD, 1430–1570 AD, 1710–1770 AD, 1800–1890 AD, and 1910–1950 AD), five flood phases (320–360 AD, 1670–710 AD, 1730–1790 AD, 1810–1860 AD, and 1880–1950 AD), and 3 oscillation periods of drought and flood events. Climate change may have been the main factor inducing droughts and floods before 1580 AD, whereas human activities may have increased the frequency of droughts and floods after the 16th century. Therefore, quantifying the impacts of natural factors and human activities on droughts and floods can provide important theoretical guidance for the prevention and reduction of future disasters.
Competition Drives Group Formation and Reduces Within Nest Relatedness in a Facultatively Social Carpenter Bee
Authors: Vickruck Jess L. , Richards Miriam H.
Published: November 2021

Animals respond to competition among kin for critical breeding resources in two ways: avoidance of direct fitness costs via dispersal of siblings to breed separately, and formation of kin-based societies in which subordinates offset direct fitness costs of breeding competition via altruism and increased indirect fitness. In the facultatively social eastern carpenter bee, nests are a critical breeding resource in perpetually short supply, leading to strong competition among females. Observations of individually marked and genotyped females in conditions of high and low resource competition demonstrate that competition leads to resource sharing and group nesting. However, in contrast to almost all known animal societies, females avoid nesting with relatives, and disperse from their natal nests to join social groups of non-relatives. This is the first example of a structured insect society with cooperation nestmates, the majority of which are unrelated; thus cooperation is more likely based on selection for direct, rather than indirect fitness. By forming social groups of non-kin, females avoid the indirect fitness costs of kin competition among sisters, yet increase their chances of successful reproduction, and thus direct fitness, when forming colonies of non-relatives.
MultiCapsNet: A General Framework for Data Integration and Interpretable Classification
Authors: Wang Lifei , Miao Xuexia , Nie Rui , Zhang Zhang , Zhang Jiang , Cai Jun
Published: November 2021

The latest progresses of experimental biology have generated a large number of data with different formats and lengths. Deep learning is an ideal tool to deal with complex datasets, but its inherent “black box” nature needs more interpretability. At the same time, traditional interpretable machine learning methods, such as linear regression or random forest, could only deal with numerical features instead of modular features often encountered in the biological field. Here, we present MultiCapsNet (https://github.com/wanglf19/MultiCapsNet), a new deep learning model built on CapsNet and scCapsNet, which possesses the merits such as easy data integration and high model interpretability. To demonstrate the ability of this model as an interpretable classifier to deal with modular inputs, we test MultiCapsNet on three datasets with different data type and application scenarios. Firstly, on the labeled variant call dataset, MultiCapsNet shows a similar classification performance with neural network model, and provides importance scores for data sources directly without an extra importance determination step required by the neural network model. The importance scores generated by these two models are highly correlated. Secondly, on single cell RNA sequence (scRNA-seq) dataset, MultiCapsNet integrates information about protein-protein interaction (PPI), and protein-DNA interaction (PDI). The classification accuracy of MultiCapsNet is comparable to the neural network and random forest model. Meanwhile, MultiCapsNet reveals how each transcription factor (TF) or PPI cluster node contributes to classification of cell type. Thirdly, we made a comparison between MultiCapsNet and SCENIC. The results show several cell type relevant TFs identified by both methods, further proving the validity and interpretability of the MultiCapsNet.
Exploring the Diverse Functional and Regulatory Consequences of Alternative Splicing in Development and Disease
Authors: Titus M. Brandon , Chang Adeline W. , Olesnicky Eugenia C.
Published: November 2021

Alternative splicing is a fundamental mechanism of eukaryotic RNA regulation that increases the transcriptomic and proteomic complexity within an organism. Moreover, alternative splicing provides a framework for generating unique yet complex tissue- and cell type-specific gene expression profiles, despite using a limited number of genes. Recent efforts to understand the negative consequences of aberrant splicing have increased our understanding of developmental and neurodegenerative diseases such as spinal muscular atrophy, frontotemporal dementia and Parkinsonism linked to chromosome 17, myotonic dystrophy, and amyotrophic lateral sclerosis. Moreover, these studies have led to the development of innovative therapeutic treatments for diseases caused by aberrant splicing, also known as spliceopathies. Despite this, a paucity of information exists on the physiological roles and specific functions of distinct transcript spliceforms for a given gene. Here, we will highlight work that has specifically explored the distinct functions of protein-coding spliceforms during development. Moreover, we will discuss the use of alternative splicing of noncoding exons to regulate the stability and localization of RNA transcripts.