bluuebunny/crossref_metadata_2025 huggingface dataset:
The Decision-Making Practices among Air Traffic Controllers during Conflict Resolution in Aviation Industry: A Case Study
Authors: Anthony Sherrie Winer , Ahmad Rusli
Published: September 2021

The study explores decision-making practices among Air Traffic Controllers (ATCOs) in the Civil Aviation Authority of Malaysia (CAAM) in Sarawak, Malaysia, using the Cynefin Framework. The study intends to identify related factors that influence decision-making practices, explore how decisions are made during conflict resolution, and describe the coping strategies in decision-making practices by ATCOs. The qualitative phenomenology case study method was used to collect data and one-to-one interviews with the ATCOs. Content analysis is used to analyse the data. The findings showed that ATCOs types and working experiences influence the way they make decisions. Decision-making among ATCOs is like the Administrative Model in which they must follow Standard Operating Procedures (SOP) as their strategies in decision-making. Findings contribute toward an understanding of current decision-making practices, which would inform relevant policies and professional training development programmes.
Quantifying Conventional Electroencephalogram Recordings and Examining its Output Computation with a Quantitative Electroencephalogram
Authors: Xavier Gregory , Su Ting Anselm , Fauzan Norsiah
Published: September 2021

Quantitative electroencephalogram enables mathematical analysis of neurological recordings while conventional electroencephalogram lacks the mathematical output; hence, its usage is limited to neurological experts. This study was to determine if quantified conventional electroencephalogram recordings were compatible and comparable with quantitative electroencephalogram recordings. A group of post-call doctors was recruited and subjected to an EEG recording using a conventional electroencephalogram followed by a quantitative electroencephalogram device. The patterns and quantified recording results were compared. A comparative analysis of the two recording sets did not find differences in the recording patterns and statistical analysis. The findings promoted the use of a readily available conventional electroencephalogram in quantitative brain wave studies and have cleared potential compatibility bias towards data merging.
Does Gender Difference Play a Significant Role in Verbal and Visuospatial Working Memory Performance?
Authors: Chan Zhi Shan , Abu Bakar Mohamad Azhari
Published: September 2021

The present study investigates gender differences in working memory performance, both verbal and visuospatial working memory performance. Quasi-experimental research was conducted individually on 32 undergraduates at a public university in Malaysia, using a reading span task and rotation span task. The performance was based on the total number of correct recalled and the total time taken. Results showed a significant gender difference in the verbal and visuospatial working memory performance. The observation was based on the total time taken, in which males performed more rapidly than females in both tasks. In terms of accuracy, female participants recalled better than their male counterparts in the verbal task, which is consistent with numerous past studies. However, no gender difference was identified in the visuospatial task performance, based on the total number of correct recalled. The study also found that male participants did not show an advantage in visuospatial abilities, contradicting findings by past studies.
Gratitude and Its Relationship to Resilience and Academic Performance among University Students
Authors: Zainoodin Nailah Najwa , Hutasuhut Ida Juliana , Abu Bakar Mohamad Azhari , Nurul Wardhani
Published: September 2021

This study examines the relationship between gratitude, resilience, and academic performance among students of a public university in Malaysia. One hundred and forty-six samples were obtained through a simple random technique (N=235). The survey employed GQ6 (Gratitude Questionnaire), Brief Resilience Scale (BRS), and self-reported grade-point average (GPA) as its measurement tools. Correlation analysis shows that gratitude has a high positive relationship with resilience and academic performance. Findings from the study support those of previous studies about the importance of gratitude in improving student’s psychological resilience and academic performances. The study suggests that adopting a sense of gratefulness and appreciation helps students overcome challenges in their educational journey at university.
Depression Survivors Among Emerging Adults: Their Healing Journey
Authors: Pui Wei Zhe , Saili Jamayah
Published: September 2021

This qualitative study explored the healing process of depression survivors among emerging adults with effective coping strategies utilised by them. A semi-structured interview was conducted on participants aged between 18-28 years old. A theme narrating the experience of the depression survivors were identified: The journey of healing - Crawling out of the quicksand. The survivors emphasised that to achieve healing, everything starts from within the self, and they had been putting in a lot of their extra efforts in helping themselves heal. They all went beyond recovery, where their efforts illustrated their focus on healing, thriving, and achieving optimal well-being upon recovery. Significantly, the relevance and applicability of the building blocks of Seligman’s PERMA model of well-being towards those efforts taken were revealed in the study.

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Efficient and Consistent Orthotopic Osteosarcoma Model by Cell Sheet Transplantation in the Nude Mice for Drug Testing
Authors: Wu Hongwei , He Zhengxi , Li Xianan , Xu Xuezheng , Zhong Wu , Bu Jie , Huang Gang
Published: September 2021

Osteosarcoma is a big challenge on clinical treatment. The breakthrough associated with osteosarcoma in basic research and translational research depends on the reliable establishment of an animal model, whereby mice are frequently used. However, a traditional animal modeling technique like tumor cell suspension injection causes batch dynamics and large mice consumption. Here, we suggested a novel approach in establishing an orthotropic osteosarcoma model in nude mice rapidly by cell sheet culture and transplantation. Our findings demonstrated that the 143b osteosarcoma cell sheet orthotopically implanted into the nude mice could form a visible mass within 10 days, whereas it took over 15 days for a similar amount of cell suspension injection to form a visible tumor mass. Living animal imaging results showed that a tumor formation rate was 100% in the cell sheet implantation group, while it was 67% in the cell suspension injection group. The formed tumor masses were highly consistent in both growth rate and tumor size. Massive bone destruction and soft tissue mass formation were observed from the micro CT analysis, suggesting the presence of osteosarcoma. The histopathological analysis demonstrated that the orthotropic osteosarcoma model mimicked the tumor bone growth, bone destruction, and the lung metastasis. These findings imply that such a cell sheet technology could be an appropriate approach to rapidly establish a sustainable orthotropic osteosarcoma model for tumor research and reduce mice consumption.
Laminin-1 Peptides Conjugated to Fibrin Hydrogels Promote Salivary Gland Regeneration in Irradiated Mouse Submandibular Glands
Authors: Nam Kihoon , dos Santos Harim T. , Maslow Frank , Trump Bryan G. , Lei Pedro , Andreadis Stelios T. , Baker Olga J.
Published: September 2021

Previous studies demonstrated that salivary gland morphogenesis and differentiation are enhanced by modification of fibrin hydrogels chemically conjugated to Laminin-1 peptides. Specifically, Laminin-1 peptides (A99: CGGALRGDN-amide and YIGSR: CGGADPGYIGSRGAA-amide) chemically conjugated to fibrin promoted formation of newly organized salivary epithelium bothin vitro(e.g.,using organoids) andin vivo(e.g.,in a wounded mouse model). While these studies were successful, the model’s usefulness for inducing regenerative patterns after radiation therapy remains unknown. Therefore, the goal of the current study was to determine whether transdermal injection with the Laminin-1 peptides A99 and YIGSR chemically conjugated to fibrin hydrogels promotes tissue regeneration in irradiated salivary glands. Results indicate that A99 and YIGSR chemically conjugated to fibrin hydrogels promote formation of functional salivary tissue when transdermally injected to irradiated salivary glands. In contrast, when left untreated, irradiated salivary glands display a loss in structure and functionality. Together, these studies indicate that fibrin hydrogel-based implantable scaffolds containing Laminin-1 peptides promote secretory function of irradiated salivary glands.
Complementarity of Digital Health and Peer Support: “This Is What’s Coming”
Authors: Tang Patrick Y. , Duni Janet , Peeples Malinda M. , Kowitt Sarah D. , Bhushan Nivedita L. , Sokol Rebeccah L. , Fisher Edwin B.
Published: September 2021

Purpose

This study examined integration of peer support and a Food and Drug Administration-cleared, diabetes management app (DMA) in diabetes self-management support as a scalable model for those with type 2 diabetes mellitus (T2DM).

Methods

Two lay health Coaches delivered telephone-based self-management support to adults (N = 43) with T2DM recruited through a primary group practice. Those eligible were offered no-cost access to DMA for the entire 6-month study. Coaches introduced DMA and contacted individuals by phone and text with frequency dependent on participant needs/preferences. DMA supported monitoring of blood glucose, carbohydrate intake, and medication use, as well as messaging personalized to participants’ medication regimens. Clinical data were extracted from DMA, electronic medical records, and Coaches’ records. Structured interviews of 12 participants, 2 Coaches, and 5 project staff were analyzed using deductive pre-identified codes (regarding adoptability, patterns of use, value added, complementarity, and sustainability) utilizing standard procedures for qualitative analysis.

Results

Of the 43 participants, 38 (88.4%) enrolled in DMA. In general, participants used both DMA and lay health coaches, averaging 144.14 DMA entries (structured, e.g., medications, and free form, e.g., “ate at a restaurant” and “stressed”) and 5.86 coach contacts over the 6-month intervention. Correlation between DMA entries and coach contacts (r = .613, p < 0.001) was consistent with complementarity as were participants’ and coaches’ observations that (a) DMA facilitated recognition of patterns and provided reminders and suggestions to achieve self-management plans, whereas (b) coaching provided motivation and addressed challenges that emerged. Mean hemoglobin A1c (A1c) declined from 9.93% to 8.86% (p < 0.001), with no pattern of coaching or DMA use significantly related to reductions. Staff identified resources to coordinate coach/DMA interventions as a major sustainability challenge.

Conclusions

DMA and peer support for diabetes management are compatible and complementary. Additional practice integration research is needed for adoption and scale-up.
Moderate-Intensity Physical Exercise Affects the Exercise Performance and Gut Microbiota of Mice
Authors: Yang Wenqian , Liu Yuqian , Yang Guang , Meng Binglin , Yi Zhicheng , Yang Guan , Chen Mingjian , Hou Pengcheng , Wang Haitao , Xu Xiaoyang
Published: September 2021

The gut microbiota is closely associated with the health of the host and is affected by many factors, including exercise. In this study, we compared the gut microbial changes and exercise performance over a 14-week period in mice that performed exercise (NE; n = 15) and mice that did not perform exercise (NC; n = 15). Mice were subjected to stool collection and exercise tests one week prior to adaptive training and after 2, 6, 10, and 14 weeks of exercise. Bacteria associated with the stool samples were assessed via Illumina-based 16S rRNA gene sequencing. While there was no significant difference in body weight between the groups (p > 0.05), the NE group had a significantly higher exercise performance from weeks 2–14 (p < 0.01) and lower fat coefficient (p < 0.01) compared with the NC group. The Shannon index of the gut microbiota in the NC group was higher than that in the NE group at weeks 6 and 10, and the Chao1 index was higher than that in the NE group at week 14. Exercise performance positively correlated with the relative abundance of Phascolarctobacterium. Grouped time series data analysis demonstrated that Bifidobacteria, Coprococcus, and one unnamed genus in the Clostridiales order were significantly increased in the NE group, which correlated with increased glucose, flavonoid, arginine, and proline metabolism. In conclusion, moderate-intensity treadmill exercise significantly increased the exercise performance of mice and changed the core bacteria and bacterial metabolic activity. These results provide a reference for studying the effects of exercise intervention and exercise performance on the gut microbiota of mice.
Valve Abnormalities, Risk Factors for Heart Valve Disease and Valve Replacement Surgery in Spondyloarthritis. A Systematic Review of the Literature
Authors: Park Hye-Sang , Laiz Ana , Sanchez-Vega Jesus , Díaz del Campo Petra , Martín-Martínez Maria Auxiliadora , Guerra-Rodríguez Mercedes , Corominas Hector
Published: September 2021

Objective: Evaluate the evidence on the abnormalities of the aortic root and heart valves, risk and prognostic factors for heart valve disease and valve replacement surgery in spondyloarthritis.

Methods: A systematic literature review was performed using Medline, EMBASE and Cochrane databases until July 2021. Prevalence, incidence, risk and prognostic factors for heart valve disease; dimension, morphology, and pathological abnormalities of the valves were analyzed. Patient characteristics (younger age, history of cardiac disease or longer disease duration) and period of realization were considered for the analysis. The SIGN Approach was used for rating the quality of the evidence of the studies.

Results: In total, 37 out of 555 studies were included. Overall, the level of evidence was low. The incidence of aortic insufficiency was 2.5–3.9‰. Hazard Ratio for aortic insufficiency was 1.8–2.0. Relative risk for aortic valve replacement surgery in ankylosing spondylitis patients was 1.22–1.46. Odds ratio for aortic insufficiency was 1.07 for age and 1.05 for disease duration. Mitral valve abnormalities described were mitral valve prolapse, calcification, and thickening. Aortic valve abnormalities described were calcification, thickening and an echocardiographic “subaortic bump.” Abnormalities of the aorta described were thickening of the wall and aortic root dilatation. The most common microscopic findings were scarring of the adventitia, lymphocytic infiltration, and intimal proliferation.

Conclusions: A higher prevalence and risk of aortic valve disease is observed in patients with ankylosing spondylitis. Studies were heterogeneous and analysis was not adjusted by potential confounders. Most studies did not define accurate outcomes and may have detected small effects as being statistically significant.
Sex Differences in the Non-infarct-Related Artery-Based Quantitative Flow Ratio in Patients With ST-Elevation Myocardial Infarction: A Retrospective Study
Authors: Hou Hongli , Zhao Qi , Qu Chao , Sun Meng , Liu Qi , Huang Xingtao , Wang Xuedong , Zhang Ruoxi , Du Lifeng , Hou Jingbo , Yu Bo
Published: September 2021

Introduction: It has been reported that sex has well-established relationships with the prevalence of coronary artery disease (CAD) and the major adverse cardiovascular events. Compared with men, the difference of coronary artery and myocardial characteristics in women has effects on anatomical and functional evaluations. Quantitative flow ratio (QFR) has been shown to be effective in assessing the hemodynamic relevance of lesions in stable coronary disease. However, its suitability in acute myocardial infarction patients is unknown. This study aimed to evaluate the sex differences in the non-infarct-related artery (NIRA)-based QFR in patients with ST-elevation myocardial infarction (STEMI).

Methods: In this study, 353 patients with STEMI who underwent angiographic cQFR assessment and interventional therapy were included. According to contrast-flow QFR (cQFR) standard operating procedures: reliable software was used to modeling the hyperemic flow velocity derived from coronary angiography in the absence of pharmacologically induced hyperemia. 353 patients were divided into two groups according to sex. A cQFR ≤0.80 was considered hemodynamically significant, whereas invasive coronary angiography (ICA) luminal stenosis ≥50% was considered obstructive. Demographics, clinical data, NIRA-related anatomy, and functional cQFR values were recorded. Clinical outcomes included the NIRA reclassification rate between men and women, according to the ICA and cQFR assessments.

Results: Women were older and had a higher body mass index (BMI) than men. The levels of diastolic blood pressure, troponin I, peak creatine kinase-MB, low-density lipoprotein cholesterol, N terminal pro B-type natriuretic peptide, stent diameter, and current smoking rate were found to be significantly lower in the female group than in the male group. Women had a lower likelihood of a positive cQFR ≤0.80 for the same degree of stenosis and a lower rate of NIRA revascularization. Independent predictors of positive cQFR included male sex and diameter stenosis (DS) >70%.

Conclusions: cQFR values differ between the sexes, as women have a higher cQFR value for the same degree of stenosis. The findings suggest that QFR variations by sex require specific interpretation, as these differences may affect therapeutic decision-making and clinical outcomes.
Determination of the Optimal Cutoff Value of Triglyceride That Corresponds to Fasting Levels in Chinese Subjects With Marked Hypertriglyceridemia
Authors: Guo Li-Ling , Zhu Li-Yuan , Xu Jin , Xie Ying-Ying , Xiang Qun-Yan , Jiang Zhe-Yi , Tan Yang-Rong , Liu Ling
Published: September 2021

The level of triglyceride (TG) ≥ 2. 3 mmol/L is suggestive of marked hypertriglyceridemia (HTG) and requires treatment with a triglyceride-lowering agent in high-risk and very high-risk patients as recommended by the 2019 ESC/EAS guidelines for the management of dyslipidemia. However, the optimal cutoff value required to diagnose non-fasting HTG that corresponds to the fasting goal level of 2.3 mmol/L in Chinese subjects is unknown. This study enrolled 602 cardiology inpatients. Blood lipid levels, including calculated non-high-density lipoprotein cholesterol (non-HDL-C) and remnant cholesterol (RC), were measured at 0, 2, and 4 h after a daily Chinese breakfast. Of these, 482 inpatients had TG levels of <2.3 mmol/L (CON group) and 120 inpatients had TG levels of ≥2.3 mmol/L (HTG group). Receiver operating characteristic (ROC) curve analysis was used to determine the cutoff values for postprandial HTG that corresponded to a target fasting level of 2.3 mmol/L. Marked hypertriglyceridemia (≥2.3 mmol/L) was found in 120 (19.9%) patients in this study population. The levels of non-fasting TG and RC increased significantly in both groups and reached the peak at 4 h after a daily meal, especially in the HTG group (p < 0.05). The optimal cutoff value of TG at 4 h, which corresponds to fasting TG of ≥2.3 mmol/L, that can be used to predict HTG, was 2.66 mmol/L. According to the new non-fasting cutoff value, the incidence of non-fasting HTG is close to its fasting level. In summary, this is the first study to determine the non-fasting cutoff value that corresponds to a fasting TG of ≥2.3 mmol/L in Chinese patients. Additionally, 2.66 mmol/l at 4 h after a daily meal could be an appropriate cutoff value that can be used to detect non-fasting marked HTG in Chinese subjects.
Degradation of Arable Soils in Central Yakutia: Negative Consequences of Global Warming for Yedoma Landscapes
Authors: Desyatkin Roman , Filippov Nikolai , Desyatkin Alexey , Konyushkov Dmitry , Goryachkin Sergey
Published: September 2021

Global warming, which is especially intensive (up to 0.08°C yr−1) in permafrost area of Central Yakutia, has dramatic consequences for scarce arable land resources in this region. In Yedoma landscapes, intense permafrost thawing on arable fields unprotected by forest vegetation transforms the surface microtopography with the formation of residual thermokarst mounds (byllars) of 6–10 m in diameter surrounded by a polygonal network of hollows of 0.3–1.5 m in depth above melting ice wedges. This process also takes place on former croplands abandoned in the recent decades because of socioeconomic reasons. It is accompanied by a significant transformation of the previously highly likely homogeneous soil cover composed of Cambic Turbic Cryosols (Sodic) into differentiated complexes of permafrost-affected Stagnic Cambisols or Calcic Solonetzes (Turbic) on the mounds and Calcic Stagnic Solonetzes (Turbic) in the microlows. Surface soil horizons on the mounds have a strongly to very strongly alkaline reaction (pH 8.5–9.5) and low (<2%) organic carbon content; a wavy line of effervescence is found at a depth of 15–30 cm. Soils in the microlows have a close to neutral reaction in the upper horizons (pH 6.2–7.5); higher organic carbon content (2–3%); more pronounced textural differentiation of the profile with the formation of typical natric Btn and, in some cases, overlying eluvial E horizons; deeper (50–60 cm) line of effervescence; and clear stagnic features in the lower part of the profile. In the case of shallow embedding by ice wedge, the lowermost part of the soil in the microlow is characterized by the low bulk density (1.04 g cm−3) because of the appearance of hollows after thawing of the ice-rich transient layer and melting of the top of ice wedges. This may be indicative of the further soil subsidence in the future and the appearance of initial thermokarst lakes (dyuedya) within the Yedoma terrain with its transformation into the alas type of landscape. Rapid thermokarst-driven development of microtopography followed by differentiation of the soil cover with increasing soil alkalinity on the microhighs and soil textural differentiation and overmoistening of deep layers in the microlows prevents the return of abandoned arable land to agriculture in Yedoma landscapes.
Exploring Formative Assessment and Co-Regulation in Kindergarten Through Interviews and Direct Observation
Authors: Braund Heather , DeLuca Christopher , Panadero Ernesto , Cheng Liying
Published: September 2021

Formative assessment practices have been theoretically connected to the development of self-regulation with mounting empirical evidence. Co-regulation is the process whereby a more capable individual (e.g., teacher or peer) attunes the behaviours, emotions, or cognitive processes of an individual (a student) to align with goals or expectations and is being recognized as a strategy for developing self-regulation. Formative assessment practices may facilitate co-regulation, however, much of the literature has focused on older student populations. This phenomenological study explored the relationship between formative assessment and co-regulation in eight Kindergarten classrooms. Eight Kindergarten teachers and four Early Childhood Educators (ECE) completed semi-structured interviews in 2019 during two time periods with each participant completing two interviews. To supplement the interviews, 56 h of classroom observations were completed in each classroom, totaling 448 h of observations across eight classrooms. Interviews were audio-recorded and transcribed verbatim. Qualitative data were analyzed thematically. Four themes emerged: 1) Authentic assessment and self-regulation practices, 2) Feedback as foundational, 3) Formative assessment and co-regulation have shared purposes, and 4) Connections between classroom assessment and co-regulation. Participants described their classroom assessment and self-regulation practices as authentic and natural for students while also providing examples of their interactions with students as a form of co-regulation. Feedback was articulated as foundational to both classroom assessment and co-regulation. Participants illustrated examples of feedback from peers (including through modified peer-assessment). Shared purposes between formative assessment and co-regulation placed students at the centre of the learning process, encouraging agentic behaviours, and scaffolding student thinking. The final theme underlined the need to broaden conceptualizations of assessment in Kindergarten. Findings suggested student agency as the bridge between classroom assessment and co-regulation, and a bidirectional, mutually supportive, relationship between formative assessment and co-regulation.
MAPbI3 Deposition by LV-PSE on TiO2 for Photovoltaic Application
Authors: Smecca Emanuele , Jena Ajay Kumar , Deretzis Ioannis , Valastro Salvatore , Sanzaro Salvatore , Mannino Giovanni , Bongiorno Corrado , La Magna Antonino , Miyasaka Tsutomu , Alberti Alessandra
Published: September 2021

Hybrid perovskites are one of the most popular materials nowadays due to their very exclusive properties. To mitigate costs, complexity, and environmental impact, in this work, we have prepared methylammonium lead iodide (MAPbI3) films by a two-step Low-Vacuum Proximity-Space-Effusion (LV-PSE). The LV-PSE method exploits the low vacuum and the short diffusion path from the precursor source to have high thermal energy and partial pressure of the sublimated species close to the substrate. To this aim, the substrate is located at a medium distance (∼2 cm) from the melting pots in a low-vacuum chamber at ∼4 × 10−2 mbar. In the first step, a PbI2 film is deposited on a substrate; in the second step, the conversion into MAPbI3 occurs via an adsorption-incorporation-migration mechanism through the evaporation of methylammonium iodide (MAI) reagents. To exploit the potential of the conversion reaction, 190 nm MAPbI3 layers are deposited on TiO2 substrates. The layers were characterized in terms of crystal structure by X-ray diffraction (XRD) analyses, which showed the exclusive presence of MAPbI3 confirming the complete conversion of the PbI2 film. Scanning Electron Microscopy (SEM) analyses revealed a flat uniform pinhole-free coverage of the substrates and good conformational coverage of the TiO2 underlayer. Transmission Electron Microscopy (TEM) analyses addressed the formation of the tetragonal phase and the absence of the amorphous phase in the film. Spectroscopic ellipsometry (SE) analyses were used to explore the optical properties and the stability of the MAPbI3 layer at different temperatures and ambient conditions. As proof of concept, solar cell architectures were prepared using TiO2 as Electron Transporting Layer (ETL), Spiro-OMeTAD as Hole Transporting Layer (HTL), and Au as a contact to exploit the new up-scalable and clean deposition method. Using just ∼190 nm thick layers, the best efficiency reached with this architecture was 6.30%.
The Optimal Time of Ovarian Reserve Recovery After Laparoscopic Unilateral Ovarian Non-Endometriotic Cystectomy
Authors: Li Huaping , Yan Bin , Wang Yanli , Shu Zhiming , Li Ping , Liu Yahong , Wang Ying , Ni Xiaohong , Liu Zhou
Published: September 2021

Background

Laparoscopic ovarian cystectomy is established as the standard surgical approach for the treatment of benign ovarian cysts. However, previous studies have shown that potential fertility can be directly impaired by laparoscopic ovarian cystectomy, diminished ovarian reserve (DOR), and even premature ovarian failure. Therefore, fertility-preserving interventions are required for benign gynecologic diseases. However, there are still little data on the time period required for recovery of ovarian reserve after the laparoscopic unilateral ovarian cystectomy, which is very important for the individualization of treatment protocols. This study aimed at investigating the time needed for the ovarian reserve to recover after laparoscopic unilateral ovarian non-endometriotic cystectomy.

Materials and Methods

Sixty-seven patients with unilateral ovarian non-endometriotic cyst from Zhoupu and Punan Hospitals who underwent laparoscopic unilateral ovarian cystectomy were recruited as a postoperative observation group (POG). Also, 69 healthy age-matched women without ovarian cyst who did not undergo surgery were recruited as a referent group (RFG). Ovarian reserve with the serum anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), estradiol (E2) levels, ovarian arterial resistance index (OARI), and antral follicle counts (AFCs) were measured on the third to fifth days of the same menstrual cycle. A postoperative 6-month follow-up of cases was performed.

Results

Compared with RFG, AFC of cyst side in the POG group showed no difference in the first, third, and sixth postoperative month (F = 0.03, F = 0.02, F = 0.55, respectively; p = 0.873, p = 0.878, p = 0.460, respectively). The OARI of cyst side in the POG group revealed no differences in the first, third, and sixth postoperative month (F = 0.73, F = 3.57, F = 1.75, respectively; p = 0.395, p = 0.061, p = 0.701, respectively). In the first month, the postoperative AMH levels significantly declined, reaching 1.88 ng/ml [interquartile range (IQR): 1.61–2.16 ng/ml] in POG and 2.57 ng/ml (IQR: 2.32–2.83 ng/ml) in RFG (F = 13.43, p = 0.000). For the data of AMH levels stratified by age, the same trend was observed between less than 25 and more than 26 years old. At this same time interval, the postoperative rate of decline was significantly lower compared to the preoperative one in POG (32.75%). The same trend was observed between the POG and RFG groups (26.67%).

Conclusions

The optimal time for recovery of ovarian reserve after laparoscopic unilateral ovarian cystectomy is estimated to be 6 months.
Association of Coronary Artery Disease and Metabolic Syndrome: Usefulness of Serum Metabolomics Approach
Authors: Jing Ziwei , Liu Liwei , Shi Yingying , Du Qiuzheng , Zhang Dingding , Zuo Lihua , Du Shuzhang , Sun Zhi , Zhang Xiaojian
Published: September 2021

Introduction

Individuals with metabolic syndrome (MetS) are at increasing risk of coronary artery disease (CAD). We investigated the common metabolic perturbations of CAD and MetS via serum metabolomics to provide insight into potential associations.

Methods

Non-targeted serum metabolomics analyses were performed using ultra high-performance liquid chromatography coupled with Q Exactive hybrid quadrupole-orbitrap high-resolution accurate mass spectrometry (UHPLC-Q-Orbitrap HRMS) in samples from 492 participants (272 CAD vs. 121 healthy controls (HCs) as cohort 1, 55 MetS vs. 44 HCs as cohort 2). Cross-sectional data were obtained when the participants were recruited from the First Affiliated Hospital of Zhengzhou University. Multivariate statistics and Student’s t test were applied to obtain the significant metabolites [with variable importance in the projection (VIP) values >1.0 and p values <0.05] for CAD and MetS. Logistic regression was performed to investigate the association of identified metabolites with clinical cardiac risk factors, and the association of significant metabolic perturbations between CAD and MetS was visualized by Cytoscape software 3.6.1. Finally, the receiver operating characteristic (ROC) analysis was evaluated for the risk prediction values of common changed metabolites.

Results

Thirty metabolites were identified for CAD, mainly including amino acids, lipid, fatty acids, pseudouridine, niacinamide; 26 metabolites were identified for MetS, mainly including amino acids, lipid, fatty acids, steroid hormone, and paraxanthine. The logistic regression results showed that all of the 30 metabolites for CAD, and 15 metabolites for MetS remained significant after adjustments of clinical risk factors. In the common metabolic signature association analysis between CAD and MetS, 11 serum metabolites were significant and common to CAD and MetS outcomes. Out of this, nine followed similar trends while two had differing directionalities. The nine common metabolites exhibiting same change trend improved risk prediction for CAD (86.4%) and MetS (90.9%) using the ROC analysis.

Conclusion

Serum metabolomics analysis might provide a new insight into the potential mechanisms underlying the common metabolic perturbations of CAD and MetS.
Epigenetic Regulation of β Cell Identity and Dysfunction
Authors: Sun Xiaoqiang , Wang Liu , Obayomi S. M. Bukola , Wei Zong
Published: September 2021

β cell dysfunction and failure are driving forces of type 2 diabetes mellitus (T2DM) pathogenesis. Investigating the underlying mechanisms of β cell dysfunction may provide novel targets for the development of next generation therapy for T2DM. Epigenetics is the study of gene expression changes that do not involve DNA sequence changes, including DNA methylation, histone modification, and non-coding RNAs. Specific epigenetic signatures at all levels, including DNA methylation, chromatin accessibility, histone modification, and non-coding RNA, define β cell identity during embryonic development, postnatal maturation, and maintain β cell function at homeostatic states. During progression of T2DM, overnutrition, inflammation, and other types of stress collaboratively disrupt the homeostatic epigenetic signatures in β cells. Dysregulated epigenetic signatures, and the associating transcriptional outputs, lead to the dysfunction and eventual loss of β cells. In this review, we will summarize recent discoveries of the establishment and disruption of β cell-specific epigenetic signatures, and discuss the potential implication in therapeutic development.
Peiminine Suppresses RANKL-Induced Osteoclastogenesis by Inhibiting the NFATc1, ERK, and NF-κB Signaling Pathways
Authors: Zhu Mengbo , Xu Wenbin , Jiang Jiuzhou , Wang Yining , Guo Yanjing , Yang Ruijia , Chang Yaqiong , Zhao Bin , Wang Zhenyu , Zhang Jianfeng , Wang Te , Shangguan Liqin , Wang Shaowei
Published: September 2021

Osteoclasts (OCs) play an important role in osteoporosis, a disease that is mainly characterized by bone loss. In our research, we aimed to identify novel approach for regulating osteoclastogenesis and thereby treating osteoporosis. Previous studies have set a precedent for screening traditional Chinese herbal extracts for effective inhibitors. Peiminine is an alkaloid extracted from the bulb of Fritillaria thunbergii Miq that reportedly has anticancer and anti-inflammatory effects. Thus, the potential inhibitory effect of peiminine on OC differentiation was investigated via a series of experiments. According to the results, peiminine downregulated the levels of specific genes and proteins in vitro and consequently suppressed OC differentiation and function. Based on these findings, we further investigated the underlying molecular mechanisms and identified the NF-κB and ERK1/2 signaling pathways as potential targets of peiminine. In vivo, peiminine alleviated bone loss in an ovariectomized mouse model.
Development and Internal Validation of a Predictive Model for Adult GH Deficiency Prior to Stimulation Tests
Authors: Bioletto Fabio , Parasiliti-Caprino Mirko , Berton Alessandro Maria , Prencipe Nunzia , Cambria Valeria , Ghigo Ezio , Grottoli Silvia , Gasco Valentina
Published: September 2021

Background

The diagnosis of adult GH deficiency (GHD) relies on a reduced GH response to provocative tests. Their diagnostic accuracy, however, is not perfect, and a reliable estimation of pre-test GHD probability could be helpful for a better interpretation of their results.

Methods

Eighty patients showing concordant GH response to two provocative tests, i.e. the insulin tolerance test and the GHRH + arginine test, were enrolled. Data on IGF-I values and on the presence/absence of other pituitary deficits were collected and integrated for the estimation of GHD probability prior to stimulation tests.

Results

An independent statistically significant association with the diagnosis of GHD was found both for IGF-I SDS (OR 0.34, 95%-CI 0.18-0.65, p=0.001) and for the presence of other pituitary deficits (OR 6.55, 95%-CI 2.06-20.83, p=0.001). A low (<25%) pre-test GHD probability could be predicted when IGF-I SDS > +0.91 in the presence of other pituitary deficits or IGF-I SDS > -0.52 in the absence of other pituitary deficits. A high (>75%) pre-test GHD probability could be predicted when IGF-I SDS < -0.82 in the presence of other pituitary deficits or IGF-I SDS < -2.26 in the absence of other pituitary deficits.

Conclusion

This is the first study that proposes a quantitative estimation of GHD probability prior to stimulation tests. Our risk class stratification represents a simple tool that could be adopted for a Bayesian interpretation of stimulation test results, selecting patients who may benefit from a second stimulation test and possibly reducing the risk of wrong GHD diagnosis.
Pathogenic and Low-Frequency Variants in Children With Central Precocious Puberty
Authors: Neocleous Vassos , Fanis Pavlos , Toumba Meropi , Gorka Barbara , Kousiappa Ioanna , Tanteles George A. , Iasonides Michalis , Nicolaides Nicolas C. , Christou Yiolanda P. , Michailidou Kyriaki , Nicolaou Stella , Papacostas Savvas S. , Christoforidis Athanasios , Kyriakou Andreas , Vlachakis Dimitrios , Skordis Nicos , Phylactou Leonidas A.
Published: September 2021

Background

Central precocious puberty (CPP) due to premature activation of GnRH secretion results in early epiphyseal fusion and to a significant compromise in the achieved final adult height. Currently, few genetic determinants of children with CPP have been described. In this translational study, rare sequence variants in MKRN3, DLK1, KISS1, and KISS1R genes were investigated in patients with CPP.

Methods

Fifty-four index girls and two index boys with CPP were first tested by Sanger sequencing for the MKRN3 gene. All children found negative (n = 44) for the MKRN3 gene were further investigated by whole exome sequencing (WES). In the latter analysis, the status of variants in genes known to be related with pubertal timing was compared with an in-house Cypriot control cohort (n = 43). The identified rare variants were initially examined by in silico computational algorithms and confirmed by Sanger sequencing. Additionally, a genetic network for the MKRN3 gene, mimicking a holistic regulatory depiction of the crosstalk between MKRN3 and other genes was designed.

Results

Three previously described pathogenic MKRN3 variants located in the coding region of the gene were identified in 12 index girls with CPP. The most prevalent pathogenic MKRN3 variant p.Gly312Asp was exclusively found among the Cypriot CPP cohort, indicating a founder effect phenomenon. Seven other CPP girls harbored rare likely pathogenic upstream variants in the MKRN3. Among the 44 CPP patients submitted to WES, nine rare DLK1 variants were identified in 11 girls, two rare KISS1 variants in six girls, and two rare MAGEL2 variants in five girls. Interestingly, the frequent variant rs10407968 (p.Gly8Ter) of the KISS1R gene appeared to be less frequent in the cohort of patients with CPP.

Conclusion

The results of the present study confirm the importance of the MKRN3-imprinted gene in genetics of CPP and its key role in pubertal timing. Overall, the results of the present study have emphasized the importance of an approach that aligns genetics and clinical aspects, which is necessary for the management and treatment of CPP.
Glucose Metabolism Disorder Induces Spermatogenic Dysfunction in Northern Pig-Tailed Macaques (Macaca leonina) With Long-Term SIVmac239 Infection
Authors: Song Tian-Zhang , Zhang Ming-Xu , Zhang Han-Dan , Wang Xue-Hui , Pang Wei , Tian Ren-Rong , Zheng Yong-Tang
Published: September 2021

Although spermatogenic dysfunction is widely found in patients with human immunodeficiency virus (HIV), the underlying reasons remain unclear. Thus far, potential hypotheses involving viral reservoirs, testicular inflammation, hormone imbalance, and cachexia show inconsistent correlation with spermatogenic dysfunction. Here, northern pig-tailed macaques (NPMs) exhibited marked spermatogenic dysfunction after long-term infection with simian immunodeficiency virus (SIVmac239), with significant decreases in Johnsen scores, differentiated spermatogonial stem cells, and testicular proliferating cells. The above hypotheses were also evaluated. Results showed no differences between SIV− and SIV+ NPMs, except for an increase in follicle stimulating hormone (FSH) during SIV infection, which had no direct effect on the testes. However, long-term SIVmac239 infection undermined pancreatic islet β cell function, partly represented by significant reductions in cellular counts and autophagy levels. Pancreatic islet β cell dysfunction led to glucose metabolism disorder at the whole-body level, which inhibited lactate production by Sertoli cells in testicular tissue. As lactate is the main energy substrate for developing germ cells, its decrease was strongly correlated with spermatogenic dysfunction. Therefore, glucose metabolism disorder appears to be a primary cause of spermatogenic dysfunction in NPMs with long-term SIVmac239 infection.
No Causal Association Between Adiponectin and the Risk of Rheumatoid Arthritis: A Mendelian Randomization Study
Authors: Chen Hanzhu , Mi Shuai , Zhu Jiahao , Jin Weidong , Li Yasong , Wang Tianle , Li Yingjun , Fan Chunhong
Published: September 2021

Background: Accumulating evidence from observational studies suggested that circulating adiponectin levels are associated with the risk of rheumatoid arthritis (RA), but the causality remains unknown. We aimed to assess the causal relationship of adiponectin with RA risk.

Methods: Based on summary statistics from large-scale genome-wide association studies (GWAS), we quantified the genetic correlation between adiponectin and RA. Then bidirectional Mendelian randomization (MR) analysis was performed to assess the causal relationship. Twenty single-nucleotide polymorphisms (SNPs) associated with adiponectin were selected as instrumental variables from a recent GWAS (n = 67,739). We applied theses SNPs to a large-scale GWAS for RA (14,361 cases and 43,923 controls) with replication using RA data from the FinnGen consortium (6,236 cases and 147,221 controls) and the UK Biobank (5,201 cases and 457,732 controls). The inverse-variance weighted (IVW) and multiple pleiotropy-robust methods were used for two-sample MR analyses.

Results: Our analyses showed no significant genetic correlation between circulating adiponectin levels and RA [rG = 0.127, 95% confidence interval (CI): –0.012 to 0.266, P = 0.074]. In MR analyses, genetically predicted adiponectin levels were not significantly associated with the RA risk (odds ratio: 0.98, 95% CI: 0.88–1.09, P = 0.669). In the reverse direction analysis, there is little evidence supporting an association of genetic susceptibility to RA with adiponectin (β: 0.007, 95% CI: –0.003 to 0.018, P = 0.177). Replication analyses and sensitivity analyses using different models yielded consistent results.

Conclusions: Our findings provided no evidence to support the causal effect of adiponectin levels on RA risk and of RA on circulating adiponectin levels.
Comutations in DDR Pathways Predict Atezolizumab Response in Non-Small Cell Lung Cancer Patients
Authors: Xiong Anning , Nie Wei , Zhou Yan , Li Changhui , Gu Kai , Zhang Ding , Chen Shiqing , Wen Fengcai , Zhong Hua , Han Baohui , Zhang Xueyan
Published: September 2021

The presence of comutations (co-mut+) in DNA damage response and repair (DDR) pathways was associated with improved survival for immune checkpoint inhibitor (ICI) therapy in non-small cell lung cancer (NSCLC). However, it remains unknown whether co-mut+ status could be a predictive biomarker for immunotherapy. We aimed to explore the predictive role of co-mut+ status in the efficacy of ICIs. A total of 853 NSCLC patients from OAK and POPLAR trials were included in the analyses for the relationship between co-mut status and clinical outcomes with atezolizumab treatment. In co-mut+ NSCLC patients, significantly prolonged progression-free survival (PFS) (p = 0.004) and overall survival (OS) (p < 0.001) were observed in atezolizumab over docetaxel. The interaction between co-mut status and treatment was significant for PFS (p for interaction = 0.010) and OS (p for interaction = 0.017). In patients with negative or low programmed death receptor-ligand 1 expression, co-mut+ status still predicted improved clinical outcomes from atezolizumab therapy. These findings suggested that co-mut status may be a promising predictor of ICI therapy in NSCLC.
High-Throughput 3D In Vitro Tumor Vasculature Model for Real-Time Monitoring of Immune Cell Infiltration and Cytotoxicity
Authors: Song Jiyoung , Choi Hyeri , Koh Seung Kwon , Park Dohyun , Yu James , Kang Habin , Kim Youngtaek , Cho Duck , Jeon Noo Li
Published: September 2021

Recent advances in anticancer therapy have shown dramatic improvements in clinical outcomes, and adoptive cell therapy has emerged as a type of immunotherapy that can modulate immune responses by transferring engineered immune cells. However, a small percentage of responders and their toxicity remain as challenges. Three-dimensional (3D) in vitro models of the tumor microenvironment (TME) have the potential to provide a platform for assessing and predicting responses to therapy. This paper describes an in vitro 3D tumor model that incorporates clusters of colorectal cancer (CRC) cells around perfusable vascular networks to validate immune-cell-mediated cytotoxicity against cancer cells. The platform is based on an injection-molded 3D co-culture model and composed of 28 microwells where separate identical vascularized cancer models can be formed. It allows robust hydrogel patterning for 3D culture that enables high-throughput experimentation. The uniformity of the devices resulted in reproducible experiments that allowed 10× more experiments to be performed when compared to conventional polydimethylsiloxane (PDMS)-based microfluidic devices. To demonstrate its capability, primary natural killer (NK) cells were introduced into the vascularized tumor network, and their activities were monitored using live-cell imaging. Extravasation, migration, and cytotoxic activity against six types of CRC cell lines were tested and compared. The consensus molecular subtypes (CMS) of CRC with distinct immune responses resulted in the highest NK cell cytotoxicity against CMS1 cancer cells. These results show the potential of our vascularized tumor model for understanding various steps involved in the immune response for the assessment of adoptive cell therapy.