bluuebunny/crossref_metadata_2025 huggingface dataset:
Gene Network Analysis Reveals Candidate Genes Related with the Hair Follicle Development in Sheep
Authors: He Junmin , Zhao Bingru , Huang Xixia , Fu Xuefeng , Liu Guifen , Tian Yuezhen , Wu Cuiling , Mao Jingyi , Liu Jing , Gun Shuangbao , Tian Kechuan
Published: February 2022

Background: Merino sheep is the most famous fine wool sheep in the world. It has high wool production and excellent wool quality, which has attracted worldwide attention. The fleece of the Merino sheep is composed predominantly of wool fibres grown from secondary wool follicles. Therefore, it is very necessary to study the development of hair follicle in order to understand the mechanism of wool. The hair follicle is a complex biological system involved in a dynamic process governed by gene regulation. The development process of hair follicle is very complex and unclear. The purpose of our research is to find candidate genes related to hair follicle development, provide molecular breeding theoretical basis for the cultivation of fine wool sheep, and provide side reference for the problems of hair loss and alopecia areata that perplex human beings.Results: We analyzed 18 mRNA data of skin tissues of 18 Merino sheep at 4 days (E65, E85, E105 and E135) and 2 days after birth (D7 and D30). We identified 7879 differentially expressed genes (DEGs) and 12623 novel-DEGs, revealed different expression patterns of these DEGs at six stages of hair follicle development, and proved their complex interactions. DEGs with stage-specific expression were significantly enriched in epidermal differentiation and development, hair follicle development and hair follicle morphogenesis, and enriched in many pathways related to hair follicle development. The key genes (LAMA5, WNT10A, KRT25, SOSTDC1, ZDHHC21, FZD1, BMP7, LRP4, TGFβ2, TMEM79, SOX10, ITGB4, ITGA6, GLI2) affecting hair follicle morphogenesis was identified by network analysis. Conclusion: This study provides a new reference of the molecular basis of hair follicle development and lays a foundation for further improving sheep hair follicle breeding. Candidate genes related to hair follicular development were found, which provided a theoretical basis of molecular breeding for the culture of fine wool sheet. These results are a valuable resource for biological investigation of fleece evolvement in animals and also supply some potential clues for understanding the molecular mechanisms of human hair development.
Genome-wide DNA methylation profiles and small non-coding RNAs signatures study of sperm with high DNA fragmentation index
Authors: Liu Minghua , Liu Peiru , Chang Yunjian , Xu Beiying , Wang Nengzhuang , Qin Lina , Zheng Jufen , Liu Yun , Wu Ligang , Yan Hongli
Published: February 2022

Background
Sperm DNA fragmentation index (DFI) is a more accurate measure of sperm quality than traditional semen analysis (sperm motility, concentration, and morphology) because DFI can better predict male fertility potential and assisted reproductive technology (ART) outcomes. However, no studies have compared the genome-wide DNA methylation profiles and small noncoding RNAs (sncRNAs) signatures of high DFI and low DFI sperm samples.
Methods
Whole-genome bisulfite sequencing (WGBS) and sncRNAs deep sequencing were performed to compare the genome-wide DNA methylation profiles and sncRNAs signatures of sperm samples of weak group(DFI > 30%) and normal group(DFI < 15%). In addition, we used the WGBS data to construct DNA methylation correlation matrices of the weak and normal group sperm.
Results
A total of 4939 diferentially methylated regions (DMRs) (3083 hypermethylated and 1856 hypomethylated) were identifed in the two group sperm samples. The hypermethylated DMRs were found to be mainly signifcantly enriched in the area of neurons and microtubule. Compared with the normal group, the global DNA methylation level of the weak group sperm showed a downward trend and the methylation correlation within the chromosomes of weak group sperm was weakened. 27 miRNAs, 151 tsRNAs and 70 rsRNAs were differently expressed between the two group sperm samples. Finally, we identified nine sncRNAs as candidate sperm quality biomarkers. In addition, the target genes of both the downregulated and upregulated miRNAs were involved in the nervous system and cell development
Conclusions
Our findings suggest that the genome-wide DNA methylation levels and sncRNAs expression of sperm were significantly correlated with sperm DFI levels. Therefore, our study provides useful biomarkers for improving the success rate of natural pregnancy and ART. The chromosomes of high DFI sperm became loose and more vulnerable to ROS attack. The increase of sperm DFI level may affect embryonic nervous system development.
Methionine regulates self-renewal, pluripotency, and cell death of GIC through cholesterol - rRNA axis
Authors: Yokogami Kiyotaka , Kikuchi Taisei , Watanabe Takashi , Nakatake Yasutaka , Yamashita Shinji , Mizuguchi Asako , Takeshima Hideo
Published: February 2022

Background. Glioma-initiating cells (GICs) are the source of glioma cells that can self-renew, have pluripotency, and are treatment-resistant, so are the starting point for relapse and eventual death despite multimodality therapy. L-[methyl-11C]methionine PET has observed high accumulation at the time of recurrence, it is important to understand the mechanism of tumor cell activation caused by the reorganization of methionine metabolism.Methods. We cultured cells in methionine-deprived culture medium for comprehensive analysis. Based on the obtained results, the possible target molecules were chemically inhibited and the respective markers were analyzed.Results. Methionine depletion markedly decreased proliferation and increased cell death of GICs. Decreased S-adenosyl-methionine, which is synthesized intracellularly by catalyzed by methionine adenosyltransferase using methionine, triggered the following: (i) global DNA demethylation, (ii) hyper-methylation of signaling pathways regulating pluripotency of stem cells, (iii) decreased expression of the core-genes and pluripotent markers of stem cells including FOXM1, SOX2, SOX4, PROM1, and OLIG2, (iv) decreased cholesterol synthesis and increased excretion mainly through decreased SREBF2, and (v) down-regulation of the large subunit of ribosomal protein configured 28S and ACA43, small nucleolar RNA guiding the pseudouridylation of 28S rRNA, which is essential for translation. In addition, inhibition of cholesterol synthesis with statin resulted in a phenotype similar to that of methionine depletion and decreases in stem cell markers and small nucleolar RNA ACA43. Moreover, suppression of FOXM1 decreased stem cell markers such as SOX4 and PROM1. The gene expression profile for cholesterol production was obtained from the Ivy Glioblastoma Atlas Project database and compared between tumor cells with relatively low methionine levels in areas of pseudopalisading arrangement around necrosis and tumor cells in the infiltrating region, showing that cells in the infiltrating region have higher capacity to produce cholesterol.Conclusions. Methionine metabolism is closely related with self-renewal, pluripotency, and cell death in GICs through modification of cholesterol biosynthesis, especially in the SREBF2-FOXM1 and ACA43 axis with modification of rRNA.
Neutralizing GM-CSF autoantibodies in pulmonary alveolar proteinosis, cryptococcal meningitis and severe nocardiosis
Authors: Salvator Hélène , Cheng Aristine , Rosen Lindsey Belle , Williamson Peter R , Bennett John E , Kashyap Anuj , Ding Li , Kwon-Chung Kyung June , Namkoong Ho , Zerbe Christa S , Holland Steven M
Published: February 2022

Background Anti GM-CSF autoantibodies (aAb) have been related to acquired pulmonary alveolar proteinosis (PAP) and described in cases of severe infections such as cryptococcosis and nocardiosis in previously healthy subjects. Whether there are different anti-GM-CSF autoantibodies corresponding to these phenotypes is unclear.MethodsPlasma samples gathered in the National Institute of Health from patients with anti GM-CSF aAb and either PAP (n=15), cryptococcal meningitis (n=15), severe nocardiosis (n=5) or overlapping phenotypes (n=6) were compared in terms of titer and neutralizing activity as assessed by inhibition of GM-CSF-induced intracellular phospho-STAT5 (pSTAT5) in monocytes.ResultsAnti GM-CSF aAb titers were higher in PAP patients compared to those with cryptococcosis (mean 495±464 ug/ml vs 197±159 ug/ml, p = 0.02); there was no difference with patients with nocardiosis (430±493 ug/ml) nor between the two type of infections. The concentration of anti-GM-CSF autoantibody resulting in 50% inhibition of GM-CSF-induced pSTAT5 (IC50) was not significantly different between groups of patients (2.46 ± 2.3, 3.7 ± 3.3 and 1.94 ± 1.1 ug/ml in PAP patients, cryptococcosis and nocardiosis patients, respectively). Nor was the concentration of GM-CSF necessary to induce 50% of maximal GM-CSF-induced pSTAT5 in presence of 10 ug/ml of anti-GM-CSF aAb (EC50). When studying longitudinal samples from patients with PAP or disseminated nocardiosis, the neutralizing effect of anti GM-CSF aAb was relatively constant over time despite targeted treatments and variations in aAb levels. ConclusionsDespite different clinical manifestations, anti-GM-CSF antibodies were similar across PAP, cryptococcosis and nocardiosis. Underlying host genetics and functional analyses may help further differentiate the biology of these conditions.
Value of Transbronchial Needle Aspiration Combined with Rapid on-Site Evaluation of Cytology in Diagnosis of Peripheral Pulmonary Lesions
Authors: liang long , Duan Hongxia , Zhu Huiyuan , Yang Huiqiong , Wang Changhui , Xie Shuanshuan , Li Xuan
Published: February 2022

Background: The diagnostic value of rapid on-site evaluation (ROSE) of cytology during endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) remains controversial. The purpose of this study was to validate the value of EUBS-TBNA combined with ROSE in the diagnosis of peripheral pulmonary lesions (PPLs).Methods: Enrolled in this study were 260 patients with nodules, masses, cavities or inflammatory lesions on pulmonary CT images, and age ranged from 23 to 83 years old. They were assigned to undergo EBUS-TBNA with ROSE (n=134) or without ROSE (n=126). The diagnostic results of ROSE during EBUS-TBNA and the final pathologic reports were analyzed and compared by utilizing SPSS21.0 software to see whether the ROSE method during EBUS-TBNA would increase the risk of procedure-related complications, improve the diagnostic yield, and evaluate the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). Results: The number of punctures in ROSE group was significantly lower than that in non-ROSE group (P<0.001). There was no significant difference in hemoptysis between the two groups (P=0.402). The overall diagnostic yield of EBUS-TBNA for malignant diseases in the ROSE-group and the non-ROSE group was 29.9% and 11.1%, respectively. The sensitivity, specificity, PPV and NPV of ROSE during EBUS-TBNA were 97.4%, 96.9%, 92.5% and 98.90% respectively, showing a high agreement with the pathological results. Youden index reached 94.3%. Conclusions: ROSE examination during EBUS-TBNA could effectively improve the diagnostic yield and reduce the number of intraoperative punctures with the diagnostic results in cytology well consistent with those of traditional pathology, and therefore is worth promoting and applying in clinical practice.
Superior capsule reconstruction versus Reverse shoulder arthroplasty in massive rotator cuff tears: A comparative study
Authors: Ohta Satoru , Ueda Yoshiyuki , Komai Osamu
Published: February 2022

Introduction: Superior capsule reconstruction (SCR) was developed in Japan in 2010 as a surgical treatment strategy for massive rotator cuff tears, This study was aimed at performing a comparative analysis of the postoperative results for SCR versus reverse shoulder arthroplasty (RSA), two surgical approaches currently used to treat massive rotator cuff tears.Materials and Methods: Patients who underwent surgeries from 2014 to 2018 and were followed up for at least 2 years were included in the study. Subsequently, the cases of Hamada classifications 1–3 were retrospectively targeted. SCR comprised 38 patients (mean age 71.4 years) and RSA comprised 24 patients (mean age 78.9 years). The Japanese Orthopaedic Association (JOA) score, University of California at Los Angeles (UCLA) score, active elevation angle, and downward external rotation and internal rotation angles before and after the surgery were evaluated and compared between the groups.Results: In postoperative group comparison (observed value), SCR significantly improved from RSA in terms of JOA score (p = 0.0060), UCLA score (p = 0.0042), elevation angle (p = 0.0070), downward external rotation (p < 0.001), and internal rotation (p < 0.001). In terms of postoperative comparison between groups (amount of change), RSA was superior in terms of JOA score (p = 0.0128) and UCLA score (p = 0.0055) and SCR showed improvement in terms of downward external rotation (p < 0.001) and internal rotation (p = 0.0016).　Conclusions: The results of treatment of massive rotator cuff tears in patients with Hamada's classification 1–3 were good for both techniques. In the postoperative comparison between the groups, downward external rotation and internal rotation showed a significant improvement in SCR in both the observed values and the amount of change.
Subfascial infiltration of 0.5% ropivacaine, but not 0.25% ropivacaine, exacerbates damage and inflammation in surgically incised abdominal muscles of rats
Authors: Shen Dandan , Sugiyama Yuki , Ishida Kumiko , Fuseya Satoshi , Ishida Takashi , Kawamata Mikito , Tanaka Satoshi
Published: February 2022

Ropivacaine-induced myotoxicity in surgically incised muscles has not been fully investigated. We evaluated the effects of infiltration anesthesia with ropivacaine on damage, inflammation and regeneration in the incised muscles of rats undergoing laparotomy. Ropivacaine or saline was infiltrated below the muscle fascia over the incised muscles. Pain-related behaviors and histological muscle damage were assessed. Macrophage infiltration at days 2 and 5 and proliferation of satellite cells at day 5 were detected by CD68 and MyoD immunostaining, respectively. Pain-related behaviors were inhibited by 0.25% and 0.5% of ropivacaine for 2 hours after surgery. Single infiltration of 0.5% ropivacaine did not induce injury in intact muscles without incision, but single and repeated infiltration of 0.5% ropivacaine significantly augmented laparotomy-induced muscle injury and increased the numbers of CD68-positve macrophages and MyoD-positive cells compared to those in rats with infiltration of saline or 0.25% ropivacaine. In contrast, there were no significant differences in them between rats with saline infusion and rats with 0.25% ropivacaine infiltration. In conclusion, single or repeated subfascial infiltration of 0.25% ropivacaine can be used without exacerbating the damage and inflammation in surgically incised muscles, but the use of 0.5% ropivacaine may be a concern because of potentially increased muscle damage.
Fractional Boundary Element Solution of Three-Temperature Thermoelectric Problems
Authors: Fahmy Mohamed , Almehmadi Mohammed , Sohail Ayesha , Subhi Fahad Al
Published: February 2022

The primary goal of this article is to propose a new fractional boundary element technique for solving nonlinear three-temperature (3T) thermoelectric problems. Analytical solution of the current problem is extremely difficult to obtain. To overcome this difficulty, a new numerical technique must be developed to solve such problem. As a result, we propose a novel fractional boundary element method (BEM) to solve the governing equations of our considered problem. Because of the advantages of the BEM solution, such as the ability to treat problems with complicated geometries that were difficult to solve using previous numerical methods, and the fact that the internal domain does not need to be discretized. As a result, the BEM can be used in a wide variety of thermoelectric applications. The numerical results show the effects of the magnetic field and the graded parameter on thermal stresses. The numerical results also validate the validity and accuracy of the proposed technique.
Tissue damage, mutagenic effect and alteration in antioxidant defense in Danio rerio (Cypriniformes: Cyprinidae) after chronic exposure to Metformin hydrochloride.
Authors: Demarco Natani Ribeiro , Zanardini Bárbara , Zazula Matheus Felipe , Sobjak Thaís , D’Arce Luciana Gregório , Guimarães Ana Tereza Bittencourt
Published: February 2022

Metformin hydrochloride (MET) is an oral medication very prescribed for patients with diabetes, with a large part of its metabolites being eliminated in the urine. Basic sanitation systems are not fully effective in removing all the contaminants, promoting contamination to rivers and supply reservoirs. The objective of this study was to test the potential acute and chronic effects of MET on the antioxidant system, mutagenicity effects and tissue damages in the bioindicator D. rerio. The animals were acclimatized and separated into six groups and exposed to different concentrations of MET (0.00, 0.25, 0.50, 0.75, 1.25 g.L− 1) over a 96 hour period to determine the LC50. In another experiment, five groups of ten animals were separated as follows: four groups for evaluation of the chronic effect of 0.45 g.L− 1 of metformin hydrochloride (15, 30, 45 and 60 days) and, a negative control group (NC). The antioxidant system and the tissue damages of the muscle samples and, the mutagenicity in the blood samples were evaluated. The presence of oxidative stress and mutagenicity, together with the activation of the antioxidant system, can be visualized up to 30 days of treatment, with intense tissue damages in 60 days and the emergence of apoptotic cells, which is evidence of the toxic potential of this drug to non-target aquatic populations.
Serum Anti-Müllerian Hormone as a Predictor of Polycystic Ovarian Syndrome among Women of Reproductive Age
Authors: Butt Muhammad Salman , Saleem Javeria , Aiman Sobia , Zakar Rubeena , Sadique Iftikhar , Fischer Florian
Published: February 2022

Background: The Polycystic Ovarian Syndrome (PCOS) affects up to a fifth of women of reproductive age and causes anovulatory subfertility. Some studies have recommended that an Anti-Müllerian Hormone (AMH) level greater than 3.8-5 ng/mL can be used for diagnosing PCOS. Therefore, this study aims to analyze the serum AMH level as a predictor of PCOS among women of reproductive age.Methods: A total of 51 women of reproductive age, recently diagnosed with PCOS (meeting the Rotterdam criteria), were selected. A cross-sectional study design was used to estimate the AMH levels among PCOS women. Baseline variables, menstrual cycle length, ovarian morphology on the ultrasound, hirsutism, sex hormones, gonadotropin, and serum AMH levels were analyzed during the follicular phase (1–5 days) of the menstrual cycle. Results: A high serum AMH level (7.23 ± 4.67 ng/ml) was recorded with normal sex hormone levels. Women with oligo-/amenorrhea had a significant mean difference for luteinizing hormone (p=0.02) and AMH levels (p=0.03) when compared with women of normal menstrual cycle length. PCOS women with high AMH levels (≥3.9 ng/ml) showed a significant difference in ovarian morphology (p<0.05) when compared with the normal AMH group. Conclusions: Serum AMH level can be used as a strong predictor for disturbance in reproductive characteristics such as menstrual cycle disturbance, polycystic ovarian morphology, and clinical signs of hyperandrogenism. An elevated serum AMH level could reflect the certainty of PCOS diagnosis among women of reproductive age with a greater number of PCOS features.
Investigation on Layered Elliptical Vibration-Assisted Cutting of Micro Groove
Authors: Zhang Chen
Published: February 2022

Elliptical vibration-assisted cutting (EVC) is a method for rapidly creating ultra-precision free-form surfaces with micro groove features, which have a wide array of industrial applications such as drag reduction, self-cleaning action, optical tuning behavior, etc. The complicated fabrication process and limited shape and deep control of micro-groove features by using EVC limit the applications of current EVC process in the fabrication of micro-groove. To overcome these limitations and improve overall performance, a layered elliptical vibration-assisted cutting(LEVC) process is presented to fabricate deep micro groove with different shape. First, a detailed layered elliptical vibration-assisted cutting method is described and a key step, the layered elliptical vibration-assisted tool path planning, is analyzed and established. Then the machining stress under the proposed LEVC method and layered conventional cutting (LCC) process were simulated and compared through finite element analysis. The simulation results show that the LEVC process can generate the lower residual stress compared to the LCC process. To validate the machining performance of the proposed LEVC process, the machining experiments for two groups of micro grooves under the proposed LEVC process and LCC process are performed. The performance tests and comparison results between the generated micro grooves under the proposed LEVC method and LCC process indicate that the proposed LEVC method is effective for generating micro groove with the controllable shape and depth. The actual experiments show that the machining capability of the developed LEVC method for micro groove is satisfactory.
Evaluation of screening parameters and machine learning models for the prediction of neonatal sepsis: A systematic review
Authors: Ezeobi Dennis Peace , Wasswa William , Musimenta Angella , Kyoyagala Stella
Published: February 2022

About 2.9 million neonates die every year worldwide, and most of these deaths occur in low-resource settings. Neonatal sepsis occurs when there is a bacterial invasion in the bloodstream; the immune system begins a systemic inflammatory response syndrome (SIRS) damaging to the body and can quickly advance to severe sepsis, multi-organ failure, and finally, death. Sepsis in neonates can progress more rapidly than in adults; therefore, a timely diagnosis is critical. The standard gold test for diagnosing neonatal sepsis is blood culture, which takes at least 72 hours. Hence, identifying key predictor variables and models that work best can help reduce neonatal morbidity and mortality. The matching articles were identified by searching the PubMed, IEEE, and Cochrane bibliography databases. For the inclusion of articles, the abstract and titles were first screened based on some predetermined criteria and then, the full-text articles were screened. Thirty-one studies met the full inclusion criteria. The duration of ROM was found to be more significant than other maternal risk factors. Heart rate and heart rate variability were found to be more significant than other neonatal clinical signs. C reactive protein and I/T ratio were found to be more significant than other laboratory tests. The main limitation is the variation in the performance measures used in the studies, which made it difficult to perform a quantitative assessment. A combination of predictor variables has been shown to strengthen neonatal sepsis prediction, as shown by some of the reviewed studies. Predictive algorithms that combine multiple variables are urgently needed to improve models for early detection, prognosis, and treatment of neonatal sepsis.
Dihydroartemisinin Extract from Artemisia hedinii inhibits spore germination of Alternaria alternata involving membrane peroxidation
Authors: You Cong , Ma YiMing , Hu Guoyuan , Yang Chunlei
Published: February 2022

Dihydroartemisinin (DHA) extract is expected to be useful as a biological pesticide for fungal disease control. This study preliminarily explored the mechanism for inhibiting spore germination of Alternaria alternate by DHA extract. The results showed that the EC50, EC90, MIC and MFC of DHA extract on the spores of A. alternata were 1.63 mg/mL, 3.14 mg/mL, 4 mg/mL and 8mg/mL, respectively. The cell membrane permeability of spores treated with DHA extract was enhanced and the integrity was decreased. Meanwhile, the contents of reactive oxygen species (ROS) and malondialdehyde (MDA) increased significantly, indicating that membrane peroxidation occurred in the spores. Significant changes in catalase (CAT) activity were observed, which also demonstrated that an oxidation reaction took place within the spores. These results indicated that the DHA extract produced ROS in the spores, which caused membrane peroxidation and destroyed the membrane, thus, inhibited spores germination of A. alternata. The antifungal activity against A. alternata mechanism of DHA could pave the way for the development of control of tobacco brown spot and other fungal diseases.
Random-Forest Model for Drug Target-Interaction Prediction via Kullbeck–Leibler Divergence
Authors: Ahn Sangjin , Lee Sieun , Kim Mi-hyun
Published: February 2022

Virtual screening has significantly improved the rate of success of early drug discovery. Recent virtual screening methods have improved along with advances in machine learning (ML) and chemical information. Among these advances, the creative extraction of drug features is important for predicting drug-target interaction (DTI), a large-scale virtual screening of known drugs. Herein, we report on Kullbeck–Leibler divergence (KLD) as a DTI feature and the feature driven classification model applicable to DTI prediction. Thus, E3FP 3D molecular fingerprints of drugs as molecular representation allowed the computation of 3D-similarities between ligands within each target (Q-Q matrix) for uniqueness of pharmacological targets and between query–ligand (Q-L vector) for DTI. The 3D similarity matrices were transformed into probability density functions using kernel density estimation (KDE) as a nonparametric estimation. Each density model could exploit the characteristics of each pharmacological target and measure the quasi-distance between ligands. Furthermore, we developed a random-forest (RF) model from the KLD feature vectors to successfully predict DTI, irrespective of whether each query belongs to a target.
Lung Cancer as a Risk Factor for Abdominal Aortic Aneurysm
Authors: Gwon Hyeran , Kang Du–Young , Park Seong Yong , Kwon Jun Seong , Lee Sang Hoon
Published: February 2022

Background
Lung cancer and abdominal aortic aneurysm (AAA) have several common risk factors. Considering that AAA is fatal, precise diagnosis and management of AAA would result in long-term survival benefit in patients with early lung cancer with good prognosis. We aimed to assess the prevalence and characteristics of AAA in patients with resectable non-small cell lung cancer (NSCLC).
Methods
Between January 2019 and November 2020, 1,019 patients with primary NSCLC treated surgically in Severance and Kangbuk Samsung Hospitals were reviewed retrospectively. We re-read abdominal-pelvic computed tomography (APCT) and positron emission tomography (PET) images and evaluated the presence of AAA. The control group comprised 2,899 cancer-free people who had a health check-up CT scan in Severance between January 2018 and December 2019. The Institutional Review Board and Ethics Committee of Severance Hospital approved this study (IRB number: 4–2021–1430).
Results
Among patients with resectable primary NSCLC patients, 39/1,019 (3.8%; odds ratio [OR], 19.19; 95% confidence interval [CI], 8.10–46.46) had AAA compared with 6/2,899 (0.2%) in the control (P < 0.001). Smokers were more likely to have AAA than non-smokers (7.0% vs 0.8%; OR, 9.57; 95% CI, 3.38–27.14; P < 0.001). In multivariable regression analysis, male sex (OR, 13.24; 95% CI, 1.50–117.48; P = 0.020), older age (OR, 1.10; 95% CI, 1.04–1.15; P < 0.001), current smoker status (OR, 4.20; 95% CI, 1.20–14.62; P = 0.024), and coronary artery obstructive disease (OR, 3.13; 95% CI, 1.48–6.62; P = 0.003) were independent risk factors for AAA development in lung cancer.
Conclusions
In our real-world study, patients with early lung cancer has a significantly higher prevalence of AAA than cancer-free controls, indicating they are a high-risk group for AAA. Therefore, we suggest patients with early NSCLC, especially smokers older than 60 years, undergo regular AAA surveillance with long term post-op follow-up for not only lung cancer but also AAA.
Papillary thyroid carcinoma as first and isolated neoplastic disease in a Lynch syndrome family member with a germline MLH1 mutation
Authors: Verrienti Antonella , Carbone Antonella , Sponziello Marialuisa , Pecce Valeria , Cito Domenico Savio , Bruno ROCCO
Published: February 2022

The Lynch syndrome (LS) is an autosomal dominant disorder characterized by a strongly increased risk of developing colorectal cancer and several extra-colonic malignancies, such as carcinomas of the endometrium, ovary, ureter, stomach, and small intestine [1]. Lynch syndrome is caused by germline mutations in mismatch repair genes (MMR)[2], mainly in MLH1 and MSH2, rarely in MSH6 and PMS2 [3,4]. Tumors usually develop at a relatively young age (<50 years). Some cancers, rare in this syndrome, can be incidentally diagnosed in one of the Lynch syndrome family members. Here we report the case of unusual presentation of papillary thyroid carcinoma in a young woman carrying the c.545+3A>G mutation (rs267607760)in MLH1gene.
Development and Validation of a Self-Care Scale for Older Adults undergoing Hip Fracture Surgery: The HFS-SC
Authors: Yeom Hye-Ah , Jeon Eun-Jeong , Sohng Kyeong-Yae
Published: February 2022

Background: The ability to take care of oneself after hip fracture surgery is important for older adults. Various scales have been developed for evaluation of this ability, but a scale specifically focusing on hip fracture has not been developed. The aim of this study was to develop and validate a scale (Hip Fracture Surgery Self-Care Scale, HFS-SC) to evaluate self-care for older adults undergoing hip fracture surgery.Methods: The scale was developed according to the guidelines by DeVellis. Initial items were derived from a literature review and individual interviews with 11 older adults who underwent hip fracture surgery. To confirm the suitability of the questions, a preliminary survey was conducted on 25 older adults. Psychometric testing was performed on 300 older adults 65 years old or over living at home after surgery for hip fracture. Psychometric properties of the scale were examined by content validity, construct validity, concurrent validity, internal consistency reliability, and test-retest reliability. Results: Exploratory factor analysis and confirmatory factor analysis demonstrated that the 18-item scale comprised five factors (functional independence, symptom recognition and management, positive mental health, participation and support in social activities, and a safe environment). The reliabilities of the scale were 0.91 for Cronbach’s alpha and 0.815 for test-retest reliability. Conclusions: The HFS-SC has acceptable validity and reliability and is expected to be useful for evaluating the levels of self-care for older adults undergoing hip fracture surgery.
lncRNA RP11-10A14.5: A Potential Prognosis Biomarker for LUAD Through Regulation on Proliferation and Metastasis
Authors: Lin Zhijie , Feng Fenglan , Liang Jiaming , Zeng Haikang , Li Jin
Published: February 2022

Lung cancer is the malignancy most commonly seen worldwide. Emerging evidences indicated that lncRNAs may serve as a prognosis marker and play important role in NSCLC tumor biology. In this work, we analyzed the prognosis value of RP11-10A14.5 using TCGA and GEPIA database and expression profiles using PCR and FISH assay. The biological roles of RP11-10A14.5 in cell growth and invasion were determined by in vitro and in vivo experiment. Expression of RP11-10A14.5 is correlated with increased clinical stage and poor survival prognosis. In vitro experiments revealed that RP11-10A14.5 was widely expressed in lung cancer cell line and mainly distributed in the cytoplasm and enhanced the growth, invasion and migration ability of NSCLC cell line. Immunofluorescence assay suggest that RP11-10A14.5 may promote EMT by downregulating E-cadherin and upregulating N-cadherin and Vimentin. Flow cytometry results suggested that RP11-10A14.5 did not significantly affect cell cycle function, but could significantly inhibit apoptosis which may further enhance metastasis cell survival. In conclusions, RP11-10A14.5 is associated with clinical stage and poor survival outcome, may serve as a diagnosis and prognosis biomarker for LUAD. Further, RP11-10A14.5 could promote LUAD cell growth and metastasis.
Randomized Clinical Trial Replication Using Real-World Data for Comparative Cardiovascular and Safety Outcomes of Empagliflozin and Sitagliptin
Authors: Jang Ha Young , Kim In-Wha , Oh Jung Mi
Published: February 2022

Background
If the same results as randomized clinical trial (RCT) can be created by conducting RWE studies, regulation decisions will be easier to assessing the effectiveness or safety of medications. In this study, we aimed to check to what extent findings from existing RCTs can be replicated in RWE study by analyzing in a reproducible process.
Methods
This study used a cohort study design to assess the effect of empagliflozin versus sitagliptin on effectiveness and safety outcomes. EMPA-REG OUTCOME trial (NCT01131676) was selected to target for replication. The inclusion/exclusion criteria and follow up method were applied as same with RCT. Major adverse cardiovascular events (MACEs) was used as a primary outcome and 15 other outcomes were also included for analysis.
Results
We followed-up (median, 2.7 years) 23,126 matched patients with type 2 diabetes mellitus (11,563 empagliflozin users and 11,563 sitagliptin users). Empagliflozin were related with a significantly decreased risk of MACEs [adjusted HR 0.87, 95% confidence interval (CI) 0.79–0.96]. The predifined estimate agreement, regulatory agreement, and standardized difference for RCT duplication were achieved. [EMPA-REG OUTCOME RCT: adjusted HR 0.86, 95% (CI) 0.74–0.99]. Of the 15 other emulation outcomes, 10 emulations were evaluated as good (all three agreements achieved), and two as moderate (two of the three agreements achieved).
Conclusions
Our study results suggest that RWE can replicate RCT results satisfactorily and have the potential for providing evidence for future regulatory decision-making. Further research is needed to determine whether RWE can be a reliable evidence in various clinical settings or specific patient groups.
Low expression of PRDM5 predicts poor prognosis of esophageal squamous cell carcinoma
Authors: Guo Jing , Yang Qiuxin , Wei Sheng , Shao Jingjing , Zhao Tianye , Guo Liyuan , Liu Jia , Chen Jia , Wang Gaoren
Published: February 2022

Background: The role of the transcription factor PRDM5 in esophageal squamous cell carcinoma (ESCC) has not been revealed. This study investigated the relationship between PRDM5 expression and survival outcome in esophageal squamous cell carcinoma and explored the mechanism in tumor development. Methods: In present study, expression of PRDM5 mRNA in esophageal squamous cell carcinoma patients was conducted using the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. The expression of PRDM5 was assessed by immunohistochemical staining. Kaplan-Meier curve and Cox regression analysis was performed to analyze the survival outcome and independent predictive factors. qRT-PCR and Methylation-specific PCR were performed to identify the mRNA level of PRDM5 and Methylation rate. Cibersort algorithm to analyze the relationship between PRDM5 expression and immune cell invasion. Western-blot was performed to confirm the expression of esophageal tumor tissues and adjacent tissues. Results: The TCGA database and GEO database show that PRDM5 mRNA level in esophageal squamous cell carcinoma adjacent tissues was higher than that of cancer tissues,and ESCC patients with high expression of PRDM5 mRNA had better overall survival.Tissue microarray showed that the protein level of PRDM5 in the adjacent tissues of patients with ESCC was higher than that in cancer tissues, and the expression level of PRDM5 was significantly correlated with the grade of clinicopathological characteristics (p<0.001). Patients with high expression of PRDM5 displayed a better OS and DFS. Cox regression analysis showed that PRDM5 was an independent risk factor and prognostic factor for ESCC patients(HR: 2.626, 95%CI: 1.824-3.781; p<0.001). The protein level of PRDM5 matched with the transcriptional level, whereas the DNA methylation affected the transcriptional level. Cibersort showed that T cells CD4 memory resting, mast cells resting, eosinophils, M2 macrophages and mast cells activated were significantly positively correlated with PRDM5 expression (P<0.05), while regulatory T cells, monocytes and dendritic cells negatively correlated with PRDM5 expression (P <0.05).Conclusion: PRDM5 can be used as a biomarker to predict the survival of ESCC patients. Furthermore, PRDM5 expression in ESCC cells may affect WNT/β-catenin signaling pathways, thus further affect the ESCC cell proliferation, migration, and invasion capacity.
Comprehensive Analysis of Epigenetic Alternations of MicroRNA and DNA Methylation Contribute to Gene Expression and Prognosis in Lung Squamous Cell Carcinoma
Authors: Li Xiaoming , Liang Yingli , Wang Huixin
Published: February 2022

Background
Early detection of lung squamous cell carcinoma (LUSC) is significantly effective in clinical management. This study aimed to identify potential LUSC biomarkers based on the epigenetic alterations of miRNAs and DNA methylation.
Methods
Analysis of expression profiles in LUSC clinical samples downloaded from The Cancer Genome Atlas (TCGA-LUSC) datasets was performed to identify differentially expressed genes (DEGs) using R packages. The biological functions were annotated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The protein-protein interaction (PPI) network of the DEGs was established through STRING (Search Tool for the Retrieval of Interacting Genes database) website, visualized by Cytoscape and further analyzed by Molecular Complex Detection (MCODE). Kaplan-meier method and univariate Cox proportional risk regression analysis were used to screen differential genes related to survival in LUSC patients. Multivariate Cox proportional risk regression analysis was used to construct a prognosis prediction model of LUSC patients with differentially expressed genes. Receiver operating characteristic (ROC) curve analysis confirmed the biomarker's specific and sensitivity.
Results
We systematically identified 96 DEGs modified by both DNA methylation and miRNA through TCGA dataset between LUSC tissues and normal tissues. KEGG pathway and GO enrichment analysis gave us an insightful view of the functions of DEMs and DMGs. Subsequently, the four-gene prognosis model were obtained, including SMAD7, MEF2C, TCF21, and TRIB1, together with clinical factors, smoking history and EvsA. Survival curve analysis indicates that the model has good predictive value for the prognosis of patients with LUSC. We also found their differential expression, especially MEF2C and TCF21, together with immune infiltration levels in B cells, CD8 + T cells, CD4 + T cells, macrophages, neutrophils, and dendritic cells, correlated with LUSC prognosis.
Conclusions
Four DEGs modified by both DNA methylation and miRNA were associated with the overall survival of LUSC patients and could be potential biomarkers to predict prognosis. MEF2C and TCF21 likely play important roles in immune cell infiltration and as prognosis biomarkers in LUSC patients with immune cell infiltration. In future research, we will explore the prognostic genes and their potential function based on the present study.
Microbiome typing in uveal melanoma is associated with plaque radiotherapy
Authors: Chen Yuning , Luo Jingting , Li Haowen , Fang Rui , Zhang Ruiheng , Liu Yueming , Li Yang , Wei Wenbin , Xiu Jingying
Published: February 2022

Background: Microbiomes have been identified in various tumor types and could affect tumor progression and treatment. As the most prevalent primary malignant eyetumor in adults, uveal melanoma (UM) has not been explored regarding its endogenous microbiome. Plaque radiotherapy (PRT) is the gold standard for the treatment of UM. Hereby, we recruited 71 UM patients, sequenced the 16S rRNA gene of their tumor tissues, and analyzed the association between UM microbiome and disease phenotypes.Results: Clear bacterial signals were observed in UM tissues by using in situ fluorescence hybridization. 523 bacterial species passed strict decontamination against 58 environmental control samples in 16S rRNA gene analysis, and these species formed three distinct types by unsupervised clustering. The UM microbiome types were significantly associated with PRT. A biomarker analysis showed that Pseudomonas and Sphingomonas were significantly enriched in the radiation group (RG) compared to the non-radiation group (NRG). A kind of radiation-resistant bacteria had a significantly higher positive rate in tumor tissues that underwent radiotherapy. We found that radioresistant bacteria Deinococcus was associated with larger tumor and later tumor stage, while Pedobacter, Bradyrhizobium, Variovorax, Pseudomonas and Stenotrophomonas were associated with later metastasis. Conclusion: There was an endogenous microbiome in UM tissues, and the distribution of microbiota was correlated with PRT and clinical features.
Carvacrol suppressed LIHC via SLC6A3
Authors: Yin Xieling , Zhang Suqing
Published: February 2022

BackgroundLiver hepatocellular carcinoma (LIHC) is the second leading cause of tumor-related death in the world and its study is urgent. Carvacrol was also found to inhibit multiple cancer types. Here we proposed that carvacrol inhibited LIHC.MethodsWe used MTT assay to determine the inhibition of carvacrol on LIHC cells. BATMAN-TCM was used to predict targets of carvacrol. These targets were further screened by their survival association and expression in cancer using TCGA data. The bioinformatic screened candidates were further validated in in-vitro experiments and clinical samples. Finally, docking models of the interaction of carvacrol and target protein were conducted.ResultsCarvacrol inhibited the viability of LIHC cell lines. 40 target genes of carvacrol were predicted, 8 of them associated with survival. 4 genes were found differentially expressed in LIHC vs. normal liver. Among these genes, the expression of SLC6A3 and SCN4A were found affected by carvacrol in LIHC cells, but only SLC6A3 correlated with the viability inhibition of carvacrol on LIHC cell lines. 5 docking models of the interaction of carvacrol and SLC6A3 were established with one that had a good binding affinity. SLC6A3 knockdown and expression revealed that SLC6A3 promoted the viability of LIHC cells.ConclusionCarvacrol inhibited the viability of LIHC cells by downregulating SLC6A3.
Perceptions and Experiences of Healthcare Personnel Regarding Violence Against Health Care: A Qualitative Multiple Case Study
Authors: Khan Muhammad Naseem , Awan Babar , Khan Mirwais , Mehboob Usman , Haq Zia Ul , Ullah Naeem , Zohaib Mohsin , Baddia Faryal , Khan Salman , Polkowski Maciej
Published: February 2022

BackgroundHealthcare workers are at high risk of facing violence all over the world. The sanctity, respect,and protection of health care beingthreatened by violence in healthcare settings. The study aims to explore the perception of healthcare personnel about violence in healthcare settings in district Peshawar.MethodsThis qualitative multiple case study uses a participatory approach to understandthe processes and themes that explain the healthcare personnel's experience of violence. Ten focus group discussions and three individual in-depth interviews were conducted with eighty-three participants recruited through purposive sampling.ResultsThree distinct recurrent themes emerged from the responses of the different stakeholders, and a consensus was reached on seven broad categories. The themes were: (a) Not all the wounds are visible: the theme describes the nature, frequency, and characteristics of violence and explores that violence is not merely any physical action taken against men or women to cause visible physical wounds, but also includes verbal or emotional abuse that attempts to hurt the feelings or affects the health of an individual. (b) But violence is never the answer: different categories, including the perpetrators of violence, causes, and contributing factors, and the consequences and effects of violence on individuals and institutions were explored and summarized that there could be many causes to provoke violence, but still violence cannot be justified. (c) Vaccine for violence: describesthe various strategies for the prevention of violence and suggests multiplemeasures at the public and institutional levels to be incorporated for a future without violence. ConclusionThe study concluded that violence against healthcare is a frequently occurring phenomenon inhealthcare settings. Most of the incidents are not highlighted as they are verbal/emotional but have far more impact on the healthcare personnel. A holistic approach was suggested for ending violence in the healthcare settings, andthe need to involve all relevant stakeholders was emphasized. The recommended measures include policy formulation, promoting awareness and education, capacity building of healthcare personnel on communication strategies/consultation skills, improved security of the healthcare settings,and positive role of media in promoting the respect of healthcare personnel. Further research should then focus on evaluating the effectiveness of these measures.
Pandemics and Oil Shocks
Authors: Mohammed Mikidadu , Barrales-Ruiz Jose A.
Published: February 2022

This paper investigates the role of the COVID-19 pandemic in oil markets, focusing on the great oil price crash in April 2020. Using a 5-variable structural vector autoregression (SVAR) model, the study identifies an oil price shock arising from the pandemic together with supply, demand, and financial market shocks to global oil markets. The results show that a pandemic shock causes a delayed decrease in oil prices. Moreover, financial market conditions that affect financial investment decisions play a significant role in oil price movements. The study also computes the forecast error variance decomposition and finds that the impact of a pandemic shock, financial speculation shock, and aggregate demand shock are crucial in the short run. The findings offer new opportunities for applications in energy research.