bluuebunny/crossref_metadata_2025 huggingface dataset:
PENGARUH KEPEMIMPINAN DAN MOTIVASI TERHADAP KINERJA PEGAWAI PADA KANTOR SEKRETARIAT DPRD KABUPATEN MUNA
Authors: Unsu Farid Ismail , Nasrul Nasrul , Suleman Nursaban Rommy
Published: February 2022

The purpose of this study were: 1). To know and identifies leadership influence on employee performance on the Parliament Secretariat Muna. 2) the effect of motivation on employee performance. 3) The effect of leadership and motivation on employee performance. The design of the study is a quantitative research. The population in this study were all employees of the Parliament Secretariat Muna totaling 39 people, using saturation sampling withdrawal. Retrieval of data in the form of interviews and questionnaires. The technique of data analysis using multiple regression models with SPSS 24. Research findings show that: 1) Leadership positive and significant effect on employee kineja. 2) Motivation positive and significant effect on employee kineja. 3) Kepempinan and motivation simultaneously positive and significant impact on employee kineja.
PENERAPAN STRATEGI PERSONAL SELLING PADA PERUSAHAAN ALDINA BAKERY KOTA TASIKMALAYA
Authors: Miati Iis
Published: February 2022

The development of the bakery business in Indonesia can now be fairly rapid. The existence of bread that is starting to be liked by all circles of society makes this bakery business a promising business. The scale of business in this field is also diverse, ranging from small, medium to large industries.The purpose of this study was to determine the application of personal selling strategies at Aldina Bakery Tasikmalaya.Personal Selling is one way to market products to increase company revenue. The increase in a company will be a support for the existence of a business to remain standing in the midst of competition with other companies, both those that have been around for a long time and with emerging competitors.The method used in this research is descriptive research method with a qualitative approach.The results obtained are that the Aldina bakery company has implemented the stages of personal selling, which have not been implemented optimally, namely: Pre-approach, Overcoming Objections and Follow-up and Maintenance. While those that have been implemented optimally are looking for prospective customers and qualifying them, presentations and demonstrations and closing salesIn addition, Aldina bakery also applies a form of personal selling including Door to door selling, Mail order, Telephone selling, Direct selling.
PENGARUH PEMAHAMAN SISTEM AKUNTANSI KEUANGAN DAERAH DAN KOMITMEN ORGANISASI TERHADAP KINERJA PENGELOLA KEUANGAN PADA ORGANISASI PERANGKAT DAERAH KABUPATEN MUNA BARAT
Authors: Anto La Ode , Hadisantoso Erwin , Nurdin Sahidin
Published: February 2022

Penelitian ini bertujuan untuk menguji dan menjelaskan pengaruh pemahaman sistem akuntansi keuangan daerah dan komitmen organisasi terhadap kinerja pengelola keuangan. Sampel pada penelitian ini berjumlah 36 orang pegawai bagian keuangan pada setiap Organisai Perangkat Daerah pemerintah Kabupaten Muna Barat. Metode pengumpulan data menggunakan kuesioner dengan skala Likert. Analisis data menggunakan metode analisis dekskriptif dan analisis linear berganda. Hasil penelitian ini menunjukan bahwa: (1) pemahaman sistem akuntansi keuangan daerah berpengaruh positif dan signifikan terhadap kinerja pengelola keuangan, (2) komitmen organisasi berpengaruh positif dan signifikan terhadap kinerja pengelola keuangan.  Hal ini menunjukkan bahwa semakin tinggi tingkat pemahaman sistem akuntansi keuangan daerah dan komitmen organisasi maka kinerja pengelola keuangan akan semakin baik
The Dual Regulation Effects of ESR1/NEDD4L on SLC7A11 in Breast Cancer Under Ionizing Radiation
Authors: Liu Rui , Liu Lin , Bian Yan , Zhang Shinan , Wang Yue , Chen Huajian , Jiang Xinyue , Li Guanghui , Chen Qing , Xue Chang , Li Mengke , Liu Lianchang , Liu Xiaodong , Ma Shumei
Published: February 2022

Radiotherapy is one of the most important treatments for breast cancer. Ferroptosis is a recently recognized form of regulated cell death that is characterized by lipid peroxidation. However, whether ionizing radiation (IR) could induce ferroptosis in breast cancer and how it works remain unknown. Bioinformatics analysis were performed to screen ferroptosis-related genes differentially expressed in breast tumor tissue and normal tissue. Then, breast cancer cell lines with different estrogen receptor (ER) phenotypes were used for studies in vitro, including ER-positive (MCF-7 and ZR-75-1) and ER-negative (MDA-MB-231) cells. The dynamic changes of mRNA and protein levels were examined after x-ray of 8 Gy by qRT-PCR and Western blotting, respectively. Immunoprecipitation (IP) was used to explore the interaction between proteins. Luciferase assay was used to analyze the transcriptional regulation effect of ESR1 on SLC7A11. BODIPY C11 and trypan blue dyes were used to determine lipid peroxidation and cell death, respectively. The result showed that the ferroptosis-related gene SLC7A11 was higher in breast cancer tissues compared with normal tissues and associated with poor survival. A positive correlation exists between ESR1 and SLC7A11 expression. ESR1 promoted SLC7A11 expression at the early stage after IR. ESR1/SLC7A11 knockdown significantly enhanced IR-induced ferroptosis in ER-positive cells. At 12 h after IR, the IP data showed the interaction between E3 ubiquitin ligase NEDD4L and SLC7A11 increased, followed by the ubiquitylation and degradation of SLC7A11. Thus, SLC7A11 expression was regulated by both ESR1 and NEDD4L, in opposite ways. For the first time, we elucidated that ESR1 and NEDD4L functioned together after radiation treatment and finally induced ferroptosis in breast cancer cells, which provides novel insight into the guidance of clinical treatment of breast cancer.
Target of Rapamycin Drives Unequal Responses to Essential Amino Acid Depletion for Egg Laying in Drosophila Melanogaster
Authors: Alves André N. , Sgrò Carla M. , Piper Matthew D. W. , Mirth Christen K.
Published: February 2022

Nutrition shapes a broad range of life-history traits, ultimately impacting animal fitness. A key fitness-related trait, female fecundity is well known to change as a function of diet. In particular, the availability of dietary protein is one of the main drivers of egg production, and in the absence of essential amino acids egg laying declines. However, it is unclear whether all essential amino acids have the same impact on phenotypes like fecundity. Using a holidic diet, we fed adult female Drosophila melanogaster diets that contained all necessary nutrients except one of the 10 essential amino acids and assessed the effects on egg production. For most essential amino acids, depleting a single amino acid induced as rapid a decline in egg production as when there were no amino acids in the diet. However, when either methionine or histidine were excluded from the diet, egg production declined more slowly. Next, we tested whether GCN2 and TOR mediated this difference in response across amino acids. While mutations in GCN2 did not eliminate the differences in the rates of decline in egg laying among amino acid drop-out diets, we found that inhibiting TOR signalling caused egg laying to decline rapidly for all drop-out diets. TOR signalling does this by regulating the yolk-forming stages of egg chamber development. Our results suggest that amino acids differ in their ability to induce signalling via the TOR pathway. This is important because if phenotypes differ in sensitivity to individual amino acids, this generates the potential for mismatches between the output of a pathway and the animal’s true nutritional status.
How Gas Generates in Pouch Cells and Affects Consumer Products
Authors: Aalund Ryan , Endreddy Bhavana , Pecht Michael
Published: February 2022

Most of today’s consumer electronic products such as cell phones, laptops, and tablets use pouch lithium-ion cells to make the most efficient use of space, compared to cylindrical and prismatic designs. However, eliminating the metal enclosure comes at a cost if the pouch cell swells due to gas generation and damages the product it is contained within. This paper presents various swollen battery examples in consumer products and how companies handle the issues, reviews the mechanisms of the gas generation, and offers solutions to prevent pouch cell swelling from affecting the devices.
Transmission-Blocking Strategies Against Malaria Parasites During Their Mosquito Stages
Authors: Yu Shasha , Wang Jing , Luo Xue , Zheng Hong , Wang Luhan , Yang Xuesen , Wang Ying
Published: February 2022

Malaria is still the most widespread parasitic disease and causes the most infections globally. Owing to improvements in sanitary conditions and various intervention measures, including the use of antimalarial drugs, the malaria epidemic in many regions of the world has improved significantly in the past 10 years. However, people living in certain underdeveloped areas are still under threat. Even in some well-controlled areas, the decline in malaria infection rates has stagnated or the rates have rebounded because of the emergence and spread of drug-resistant malaria parasites. Thus, new malaria control methods must be developed. As the spread of the Plasmodium parasite is dependent on the part of its life cycle that occurs in mosquitoes, to eliminate the possibility of malaria infections, transmission-blocking strategies against the mosquito stage should be the first choice. In fact, after the gametocyte enters the mosquito body, it undergoes a series of transformation processes over a short period, thus providing numerous potential blocking targets. Many research groups have carried out studies based on targeting the blocking of transmission during the mosquito phase and have achieved excellent results. Meanwhile, the direct killing of mosquitoes could also significantly reduce the probability of malaria infections. Microorganisms that display complex interactions with Plasmodium, such as Wolbachia and gut flora, have shown observable transmission-blocking potential. These could be used as a biological control strategy and play an important part in blocking the transmission of malaria.
Clinical- and Cost Effectiveness of a Guided Internet-Based Intervention for Children (12–18 Years) of Parents With Mental Disorders (iCHIMPS): Study Protocol of a Multicentered Cluster-Randomized Controlled Trial
Authors: Dülsen Patrick , Barck Katja , Daubmann Anne , Höller Alexandra , Zeidler Jan , Kilian Reinhold , Wiegand-Grefe Silke , Baumeister Harald
Published: February 2022

Introduction

Children of parents with mental disorders have a high chance of developing a mental disorder themselves. However, this at-risk group is regularly overlooked and typically not seen by any mental health professionals. Internet- and mobile-based interventions (IMIs) can provide a means of promoting mental health for children of parents with mental disorders.

Objective

The introduced study will evaluate the clinical- and cost-effectiveness of the iCHIMPS IMI in promoting mental health for children of parents with mental disorders.

Methods

A two-armed multicentered cluster-randomized controlled trial (cRCT) comparing the clinical- and cost-effectiveness of the iCHIMPS IMI in the intervention group (IG) to a treatment-as-usual (TAU) control group will be conducted. Recruitment will be handled at currently 21 adult mental health clinics throughout Germany. Participating families will be randomly divided into the two groups until the final sample size of 306 participating adolescents (age 12–18) has been reached. The adolescents in the intervention group will receive access to the IMI and can take part in up to eight intervention modules. Assessment will be conducted during the recruitment (baseline), 1-month, 2-months, and 6-month post-inclusion. Primary outcome is the mental health of the participating adolescents at 6-months post-inclusion as measured by the Youth Self Report score. Secondary self-report outcomes are mental wellbeing, self-efficacy, coping strategies and negative effects as well as mental health of the adolescents as reported by their parent(s). Included moderators are sociodemographic characteristics, working alliance, social support and the mental health diagnoses of the parents. Statistical analyses will be conducted on the intention-to-treat principle as well as with additional per-protocol analyses. Additionally, the cost-effectiveness as well as qualitative data concerning the adherence, acceptance, and feasibility of the IMI will be analyzed.

Discussion

The iCHIMPS cRCT examines the clinical- as well as cost-effectiveness of the iCHIMPS mental health promotion IMI for children of parents with mental disorders. This provides the opportunity to gain insights into an innovative as well as time- and location-independent form of support for this often-overlooked at-risk group. Additionally, the larger CHIMPS-NET project allows comparisons between internet-based and face-to-face interventions for a similar target group.

Clinical Trial Registration

www.ClinicalTrials.gov, identifier: DRKS00025158.
Machine Learning for Outcome Prediction in First-Line Surgery of Prolactinomas
Authors: Huber Markus , Luedi Markus M. , Schubert Gerrit A. , Musahl Christian , Tortora Angelo , Frey Janine , Beck Jürgen , Mariani Luigi , Christ Emanuel , Andereggen Lukas
Published: February 2022

Background

First-line surgery for prolactinomas has gained increasing acceptance, but the indication still remains controversial. Thus, accurate prediction of unfavorable outcomes after upfront surgery in prolactinoma patients is critical for the triage of therapy and for interdisciplinary decision-making.

Objective

To evaluate whether contemporary machine learning (ML) methods can facilitate this crucial prediction task in a large cohort of prolactinoma patients with first-line surgery, we investigated the performance of various classes of supervised classification algorithms. The primary endpoint was ML-applied risk prediction of long-term dopamine agonist (DA) dependency. The secondary outcome was the prediction of the early and long-term control of hyperprolactinemia.

Methods

By jointly examining two independent performance metrics – the area under the receiver operating characteristic (AUROC) and the Matthews correlation coefficient (MCC) – in combination with a stacked super learner, we present a novel perspective on how to assess and compare the discrimination capacity of a set of binary classifiers.

Results

We demonstrate that for upfront surgery in prolactinoma patients there are not a one-algorithm-fits-all solution in outcome prediction: different algorithms perform best for different time points and different outcomes parameters. In addition, ML classifiers outperform logistic regression in both performance metrics in our cohort when predicting the primary outcome at long-term follow-up and secondary outcome at early follow-up, thus provide an added benefit in risk prediction modeling. In such a setting, the stacking framework of combining the predictions of individual base learners in a so-called super learner offers great potential: the super learner exhibits very good prediction skill for the primary outcome (AUROC: mean 0.9, 95% CI: 0.92 – 1.00; MCC: 0.85, 95% CI: 0.60 – 1.00). In contrast, predicting control of hyperprolactinemia is challenging, in particular in terms of early follow-up (AUROC: 0.69, 95% CI: 0.50 – 0.83) vs. long-term follow-up (AUROC: 0.80, 95% CI: 0.58 – 0.97). It is of clinical importance that baseline prolactin levels are by far the most important outcome predictor at early follow-up, whereas remissions at 30 days dominate the ML prediction skill for DA-dependency over the long-term.

Conclusions

This study highlights the performance benefits of combining a diverse set of classification algorithms to predict the outcome of first-line surgery in prolactinoma patients. We demonstrate the added benefit of considering two performance metrics jointly to assess the discrimination capacity of a diverse set of classifiers.
Identifying and Validating of an Autophagy-Related Gene Signature for the Prediction of Early Relapse in Breast Cancer
Authors: Min Yu , Feng Yang , Luo Haojun , Hu Daixing , Wei Xiaoyuan , He Danshuang , Yin Guobing , Fan Shenghao
Published: February 2022

Background

Compelling evidence has demonstrated the pivotal role of autophagy in the prognosis of breast cancer. Breast cancer (BC) patients with early relapse consistently exhibited worse survival.

Methods

The autophagy-related genes were derived from the Human Autophagy Database (HADb) and high-sequencing data were obtained from The Cancer Genome Atlas (TCGA). Discrepantly expressed autophagy genes (DEAGs) between early relapse and long-term survival groups were performed using the Linear Models for Microarray data (LIMMA) method. Lasso Cox regression analysis was conducted for the selection of the 4-gene autophagy-related gene signature. GSE42568 and GSE21653 databases were enrolled in this study for the external validation of the signature. Then patients were divided into high and low-risk groups based on the specific score formula. GSEA was used to discover the related signaling pathway. The Kaplan-Meier curves and the receiver operating characteristic (ROC) curves were used to evaluate the discrimination and accuracy of the 4-gene signature.

Results

A signature composed of four autophagy-related mRNA including APOL1, HSPA8, SIRT1, and TP73, was identified as significantly associated with the early relapse in BC patients. Time-dependent receiver-operating characteristic at 1 year suggested remarkable accuracy of the signature [area under the curve (AUC = 0.748)]. The risk score model based on the autophagy-related signature showed favorable predicting value in 1-, 2-, and 3-year relapse-free survival (RFS) in training and two validating cohorts. The GSEA displayed gene sets were remarkably enriched in carcinogenic activation pathways and autophagy-related pathways. The nomogram involving three variables (progesterone receptor status, T stage, and 4-gene signature) exhibited relatively good discrimination with a C-index of 0.766.

Conclusions

Our study establishes an autophagy-related 4-gene signature that can effectively stratify the high-risk and low-risk BC patients for early relapse. Combined with the clinicopathological variables, the signature could significantly help oncologists tailor more efficient treatment strategies for BC patients.
Financial Inclusion, Technological Innovations, and Environmental Quality: Analyzing the Role of Green Openness
Authors: Ahmad Mahmood , Ahmed Zahoor , Bai Yang , Qiao Guitao , Popp József , Oláh Judit
Published: February 2022

Undoubtedly, financial inclusion (FIN) contributes to economic development by enabling individuals and businesses, particularly small and medium enterprises, to access financial services. Financial inclusion may also have environmental implications; however, limited studies have looked into the nexus between financial inclusion and environmental quality. Also, the possible impacts of technological innovation and green openness remain unexplored in this nexus. In this context, this article probes the relationship between financial inclusion, technological innovation, green openness, and CO2 emissions in BRICS countries while controlling for economic growth and energy consumption. Using the panel times series data from 2004 to 2018, this study uses advanced econometric techniques for empirical analysis robust to cross-sectional dependency and slope heterogeneity. The empirical results unveiled that FIN contributes to environmental degradation in BRICS countries. In contrast, technological innovation and green openness pose mitigating effects on emissions, thus promoting environmental sustainability. Environmental degradation is evidenced to enhance due to rising economic growth and energy utilization. Financial inclusion, technological innovation, and green openness Granger cause CO2 emissions, but not the other way around. Further, technological innovation, green openness, and financial inclusion Granger cause each other. Based on the empirical results, this study recommends that BRICS countries should promote technological innovation, green openness, and at the same time, integrate financial inclusion with environmental policies to achieve climate-related goals.
Ultra Low-Coverage Whole-Genome Sequencing as an Alternative to Genotyping Arrays in Genome-Wide Association Studies
Authors: Chat Vylyny , Ferguson Robert , Morales Leah , Kirchhoff Tomas
Published: February 2022

An array-based genotyping approach has been the standard practice for genome-wide association studies (GWASs); however, as sequencing costs plummet over the past years, ultra low-coverage whole-genome sequencing (ulcWGS <0.5× coverage) has emerged as a promising alternative that provides superior genomic coverage with substantial reduction of genotyping cost. To evaluate the potential utility of ulcWGS, we performed a whole-genome sequencing (WGS) of 72 European individuals to a target coverage of 0.4× and compared its performance with the widely used Infinium Global Screening Multi-Disease Array (GSA-MD). We showed that the number of variants captured by ulcWGS is comparable with imputed GSA-MD platform, particularly for low-frequency (95.5%) and common variants (99.9%), with high imputation R2 accuracy (mean 0.93 for SNPs and 0.86 for indels). Using deep-coverage 30× WGS as the “truth” genotypes, we found that ulcWGS has higher overall nonreference genotype concordance compared with imputed GSA-MD for both SNPs (0.90 vs. 0.88) and indels (0.86 vs. 0.83). In addition, ulcWGS proved to be as sensitive as the genotyping-based method in sex imputation and ancestry prediction producing similar principal component (PC) scores. Our findings provide important evidence that the cost efficient ulcWGS of <0.5× generates high genotype accuracy, outperforming the standard genotyping arrays, making it an attractive alternative to the array-based method in next-generation GWAS design.
Non-Darwinian Molecular Biology
Authors: Palazzo Alexander F. , Kejiou Nevraj S.
Published: February 2022

With the discovery of the double helical structure of DNA, a shift occurred in how biologists investigated questions surrounding cellular processes, such as protein synthesis. Instead of viewing biological activity through the lens of chemical reactions, this new field used biological information to gain a new profound view of how biological systems work. Molecular biologists asked new types of questions that would have been inconceivable to the older generation of researchers, such as how cellular machineries convert inherited biological information into functional molecules like proteins. This new focus on biological information also gave molecular biologists a way to link their findings to concepts developed by genetics and the modern synthesis. However, by the late 1960s this all changed. Elevated rates of mutation, unsustainable genetic loads, and high levels of variation in populations, challenged Darwinian evolution, a central tenant of the modern synthesis, where adaptation was the main driver of evolutionary change. Building on these findings, Motoo Kimura advanced the neutral theory of molecular evolution, which advocates that selection in multicellular eukaryotes is weak and that most genomic changes are neutral and due to random drift. This was further elaborated by Jack King and Thomas Jukes, in their paper “Non-Darwinian Evolution”, where they pointed out that the observed changes seen in proteins and the types of polymorphisms observed in populations only become understandable when we take into account biochemistry and Kimura’s new theory. Fifty years later, most molecular biologists remain unaware of these fundamental advances. Their adaptionist viewpoint fails to explain data collected from new powerful technologies which can detect exceedingly rare biochemical events. For example, high throughput sequencing routinely detects RNA transcripts being produced from almost the entire genome yet are present less than one copy per thousand cells and appear to lack any function. Molecular biologists must now reincorporate ideas from classical biochemistry and absorb modern concepts from molecular evolution, to craft a new lens through which they can evaluate the functionality of transcriptional units, and make sense of our messy, intricate, and complicated genome.
Global Characterization of Peripheral B Cells in Parkinson’s Disease by Single-Cell RNA and BCR Sequencing
Authors: Wang Pingping , Luo Meng , Zhou Wenyang , Jin Xiyun , Xu Zhaochun , Yan Shi , Li Yiqun , Xu Chang , Cheng Rui , Huang Yan , Lin Xiaoyu , Yao Lifen , Nie Huan , Jiang Qinghua
Published: February 2022

Immune system plays important roles in the pathogenesis of Parkinson’s disease (PD). However, the role of B cells in this complex disease are still not fully understood. B cells produce antibodies but can also regulate immune responses. In order to decode the relative contribution of peripheral B cell subtypes to the etiology of PD, we performed single cell RNA and BCR sequencing for 10,466 B cells from 8 PD patients and 6 age-matched healthy controls. We observed significant increased memory B cells and significant decreased naïve B cells in PD patients compared to healthy controls. Notably, we also discovered increased IgG and IgA isotypes and more frequent class switch recombination events in PD patients. Moreover, we identified preferential V and J gene segments of B cell receptors in PD patients as the evidence of convergent selection in PD. Finally, we found a marked clonal expanded memory B cell population in PD patients, up-regulating both MHC II genes (HLA-DRB5, HLA-DQA2 and HLA-DPB1) and transcription factor activator protein 1 (AP-1), suggesting that the antigen presentation capacity of B cells was enhanced and B cells were activated in PD patients. Overall, this study conducted a comprehensive analysis of peripheral B cell characteristics of PD patients, which provided novel insights into the humoral immune response in the pathogenesis of PD.
Perceived Stigma and Self-Efficacy of Patients With Inflammatory Bowel Disease-Related Stoma in China: A Cross-Sectional Study
Authors: Wang Yuting , Li Shuyan , Gong Jianfeng , Cao Lei , Xu Dingting , Yu Qiao , Wang Xiaoying , Chen Yan
Published: February 2022

Background

Patients with inflammatory bowel disease (IBD)-related stoma face physical, psychological, and social adjustment challenges. However, knowledge about stigmatization and self-management, which is important for clinical care and patient education strategies, is lacking.

Objective

To evaluate the level of stigma and self-management ability of Chinese patients with IBD-related stoma using an online questionnaire.

Methods

Participants were recruited from two general hospitals in mainland China and the internet platforms of the China Crohn's and Colitis Foundation (CCCF). Participants completed a questionnaire, which gathered data on sociodemographic, clinical, and experience in online groups, self-efficacy scale, and social impact scale. The influencing factors of self-efficacy and perceived stigma were assessed by stepwise multivariate regression analyses.

Results

One hundred and seventy-six respondents were included. Most of the respondents (78/176, 44.32%) spent between 500 and 999 RMB ($77–153) on ostomy care accessories monthly. Three patients reported using homemade ostomy products. The average score on the self-efficacy scale was 75.79 ± 23.91, which reflected a moderate level of self-efficacy, and 69 (39.2%) respondents had low-level self-efficacy. The average social impact scale score was 62.76 ± 12.69, which reflected a moderate level of perceived stigma. Forty-three (24.43%) patients experienced severe levels of perceived stigma. Stepwise multivariate regression analysis revealed that self-efficacy was associated with educational level (P = 0.007), whereas stigma was associated with nursing privacy (P = 0.021) and acceptance by the closest person (P = 0.005). A total of 91% of respondents who participated in online peer support groups believed the groups were helpful for disease management.

Conclusions

Chinese patients with IBD-related stoma reported a moderate degree of perceived stigma; their level of self-efficacy was low to moderate. High educational level was associated with high self-efficacy. Notably, acceptance of the stoma by the closest person was an influencing factor protecting patients from perceived stigma. Interventions aimed at improving patient education, reducing economic burden, and strengthening social support should be considered to help improve the living conditions of patients with IBD-related stoma.
Inflammation and Cardiovascular Diseases in the Elderly: The Role of Epicardial Adipose Tissue
Authors: Conte Maddalena , Petraglia Laura , Poggio Paolo , Valerio Vincenza , Cabaro Serena , Campana Pasquale , Comentale Giuseppe , Attena Emilio , Russo Vincenzo , Pilato Emanuele , Formisano Pietro , Leosco Dario , Parisi Valentina
Published: February 2022

Human aging is a complex phenomenon characterized by a wide spectrum of biological changes which impact on behavioral and social aspects. Age-related changes are accompanied by a decline in biological function and increased vulnerability leading to frailty, thereby advanced age is identified among the major risk factors of the main chronic human diseases. Aging is characterized by a state of chronic low-grade inflammation, also referred as inflammaging. It recognizes a multifactorial pathogenesis with a prominent role of the innate immune system activation, resulting in tissue degeneration and contributing to adverse outcomes. It is widely recognized that inflammation plays a central role in the development and progression of numerous chronic and cardiovascular diseases. In particular, low-grade inflammation, through an increased risk of atherosclerosis and insulin resistance, promote cardiovascular diseases in the elderly. Low-grade inflammation is also promoted by visceral adiposity, whose accumulation is paralleled by an increased inflammatory status. Aging is associated to increase in epicardial adipose tissue (EAT), the visceral fat depot of the heart. Structural and functional changes in EAT have been shown to be associated with several heart diseases, including coronary artery disease, aortic stenosis, atrial fibrillation, and heart failure. EAT increase is associated with a greater production and secretion of pro-inflammatory mediators and neuro-hormones, so that thickened EAT can pathologically influence, in a paracrine and vasocrine manner, the structure and function of the heart and is associated to a worse cardiovascular outcome. In this review, we will discuss the evidence underlying the interplay between inflammaging, EAT accumulation and cardiovascular diseases. We will examine and discuss the importance of EAT quantification, its characteristics and changes with age and its clinical implication.
Mechanism-Driven Modeling to Aid Non-invasive Monitoring of Cardiac Function via Ballistocardiography
Authors: Zaid Mohamed , Sala Lorenzo , Ivey Jan R. , Tharp Darla L. , Mueller Christina M. , Thorne Pamela K. , Kelly Shannon C. , Silva Kleiton Augusto Santos , Amin Amira R. , Ruiz-Lozano Pilar , Kapiloff Michael S. , Despins Laurel , Popescu Mihail , Keller James , Skubic Marjorie , Ahmad Salman , Emter Craig A. , Guidoboni Giovanna
Published: February 2022

Left ventricular (LV) catheterization provides LV pressure-volume (P-V) loops and it represents the gold standard for cardiac function monitoring. This technique, however, is invasive and this limits its applicability in clinical and in-home settings. Ballistocardiography (BCG) is a good candidate for non-invasive cardiac monitoring, as it is based on capturing non-invasively the body motion that results from the blood flowing through the cardiovascular system. This work aims at building a mechanistic connection between changes in the BCG signal, changes in the P-V loops and changes in cardiac function. A mechanism-driven model based on cardiovascular physiology has been used as a virtual laboratory to predict how changes in cardiac function will manifest in the BCG waveform. Specifically, model simulations indicate that a decline in LV contractility results in an increase of the relative timing between the ECG and BCG signal and a decrease in BCG amplitude. The predicted changes have subsequently been observed in measurements on three swine serving as pre-clinical models for pre- and post-myocardial infarction conditions. The reproducibility of BCG measurements has been assessed on repeated, consecutive sessions of data acquisitions on three additional swine. Overall, this study provides experimental evidence supporting the utilization of mechanism-driven mathematical modeling as a guide to interpret changes in the BCG signal on the basis of cardiovascular physiology, thereby advancing the BCG technique as an effective method for non-invasive monitoring of cardiac function.
Whole-Genome Shotgun Sequencing for Nasopharyngeal Microbiome in Pre-school Children With Recurrent Wheezing
Authors: Song Yuping , Hou Jinpao , Kwok Jamie Sui Lam , Weng Haoyi , Tang Man Fung , Wang Maggie Haitian , Leung Agnes Sze Yin , Tao Kin Pong , Wong Gary Wing Kin , Chan Renee Wan Yi , Tsui Stephen Kwok Wing , Leung Ting Fan
Published: February 2022

Microbiome mediates early life immune deviation in asthma development. Recurrent wheeze (RW) in pre-school years is a risk factor for asthma diagnosis in school-age children. Dysbiosis exists in asthmatic airways, while its origin in pre-school years and relationship to RW is not clearly defined. This study investigated metagenomics of nasopharyngeal microbiome in pre-school children with RW. We applied whole-genome shotgun sequencing and human rhinovirus (HRV) detection on nasopharyngeal samples collected from three groups of pre-school children: (i) RW group: 16 children at-risk for asthma who were hospitalized for RW, (ii) inpatient control (IC): 18 subjects admitted for upper respiratory infection, and (iii) community control (CC): 36 children without respiratory syndromes. Sequence reads were analyzed by MetaPhlAn2 and HUMAnN2 algorithm for taxonomic and functional identification. Linear discriminant analysis effect size (LEfSe) analysis was used to identify discriminative features. We identified that Moraxella catarrhalis and Dolosigranulum pigrum were predominant species in nasopharynx. RW had lower alpha diversity (Shannon diversity index) than CC (0.48 vs. 1.07; Padj = 0.039), characterized by predominant Proteobacteria. LEfSe analysis revealed D. pigrum was the only discriminative species across groups (LDA = 5.57, P = 0.002), with its relative abundance in RW, IC, and CC being 9.6, 14.2, and 37.3%, respectively (P < 0.05). LEfSe identified five (ribo)nucleotides biosynthesis pathways to be group discriminating. Adjusting for HRV status, pre-school children with RW have lower nasopharyngeal biodiversity, which is associated with Proteobacteria predominance and lower abundance of D. pigrum. Along with discriminative pathways found in RW and CC, these microbial biomarkers help to understand RW pathogenesis.
The Role of Environmental Processes and Geographic Distance in Regulating Local and Regionally Abundant and Rare Bacterioplankton in Lakes
Authors: Pearman John K. , Thomson-Laing Georgia , Thomson-Laing Jacob , Thompson Lucy , Waters Sean , Reyes Lizette , Howarth Jamie D. , Vandergoes Marcus J. , Wood Susanna A.
Published: February 2022

Bacteria are vital components of lake systems, driving a variety of biogeochemical cycles and ecosystem services. Bacterial communities have been shown to have a skewed distribution with a few abundant species and a large number of rare species. The contribution of environmental processes or geographic distance in structuring these components is uncertain. The discrete nature of lakes provides an ideal test case to investigate microbial biogeographical patterns. In the present study, we used 16S rRNA gene metabarcoding to examine the distribution patterns on local and regional scales of abundant and rare planktonic bacteria across 167 New Zealand lakes covering broad environmental gradients. Only a few amplicon sequence variants (ASVs) were abundant with a higher proportion of rare ASVs. The proportion of locally abundant ASVs was negatively correlated with the percentage of high productivity grassland in the catchment and positively with altitude. Regionally rare ASVs had a restricted distribution and were only found in one or a few lakes. In general, regionally abundant ASVs had higher occupancy rates, although there were some with restricted occupancy. Environmental processes made a higher contribution to structuring the regionally abundant community, while geographic distances were more important for regionally rare ASVs. A better understanding of the processes structuring the abundance and distribution of bacterial communities within lakes will assist in understand microbial biogeography and in predicting how these communities might shift with environmental change.
Filter Plating Method for Rendering Picocyanobacteria Cultures Free of Heterotrophic Bacterial Contaminants and Clonal
Authors: Kearney Sean M. , Coe Allison , Castro Kurt G. , Chisholm Sallie W.
Published: February 2022

Isolates of the marine picocyanobacteria, Prochlorococcus and Synechococcus, are often accompanied by diverse heterotrophic “contaminating” bacteria, which can act as confounding variables in otherwise controlled experiments. Traditional microbiological methods for eliminating contaminants, such as direct streak-plating, are often unsuccessful with this particular group of microorganisms. While they will grow in pour plates, colonies often remain contaminated with heterotrophic bacteria that can migrate through the soft agar. Additionally, axenic clones of picocyanobacteria can be recovered via dilution-to-extinction in liquid medium, but the efficiency of recovery is low, often requiring large numbers of 96-well plates. Here, we detail a simple and effective protocol for rendering cultures of Synechococcus and Prochlorococcus strains free of bacterial contaminants while at the same time yielding clonal isolates. We build on the fact that co-culture with specific heterotrophs—“helper heterotrophs”—is often necessary to grow colonies of picocyanobacteria from single cells in agar. Suspecting that direct physical contact between the helper and the picocyanobacterial cells was not necessary for the “helper effect,” we developed a protocol in which the helper cells are embedded in soft agar pour plates, a filter overlaid on the surface, and a picocyanobacterial culture is diluted and then spotted on top of the filter. With this approach, motile contaminants cannot swim to the colonies, and it is possible to obtain the expected number of colonies from a given input (i.e., a Poisson distribution of colonies with an expected value equal to the input number of cells), thus ensuring clonal colonies. Using this protocol, we rendered three strains of Synechococcus, two strains of Prochlorococcus, and 19 new strains of Synechococcus from coastal seawater clonal and free of heterotrophic bacteria. The simplicity of this approach should expand the repertoire of axenic picocyanobacterial strains available for controlled physiological experiments. It will also enable the study of microdiversity in populations of picocyanobacteria by facilitating large-scale isolation of picocyanobacterial clones from a single source, including direct isolation from natural seawater.
Integrative Assessments on Molecular Taxonomy of Acidiferrobacter thiooxydans ZJ and Its Environmental Adaptation Based on Mobile Genetic Elements
Authors: Ma Liyuan , Yang Weiyi , Huang Shanshan , Liu Rui , Li Huiying , Huang Xinping , Xiong Junming , Liu Xueduan
Published: February 2022

Acidiferrobacter spp. are facultatively anaerobic acidophiles that belong to a distinctive Acidiferrobacteraceae family, which are similar to Ectothiorhodospiraceae phylogenetically, and are closely related to Acidithiobacillia class/subdivision physiologically. The limited genome information has kept them from being studied on molecular taxonomy and environmental adaptation in depth. Herein, Af. thiooxydans ZJ was isolated from acid mine drainage (AMD), and the complete genome sequence was reported to scan its genetic constitution for taxonomic and adaptative feature exploration. The genome has a single chromosome of 3,302,271 base pairs (bp), with a GC content of 63.61%. The phylogenetic tree based on OrthoANI highlighted the unique position of Af. thiooxydans ZJ, which harbored more unique genes among the strains from Ectothiorhodospiraceae and Acidithiobacillaceae by pan-genome analysis. The diverse mobile genetic elements (MGEs), such as insertion sequence (IS), clustered regularly interspaced short palindromic repeat (CRISPR), prophage, and genomic island (GI), have been identified and characterized in Af. thiooxydans ZJ. The results showed that Af. thiooxydans ZJ may effectively resist the infection of foreign viruses and gain functional gene fragments or clusters to shape its own genome advantageously. This study will offer more evidence of the genomic plasticity and improve our understanding of evolutionary adaptation mechanisms to extreme AMD environment, which could expand the potential utilization of Af. thiooxydans ZJ as an iron and sulfur oxidizer in industrial bioleaching.
Soil Microbiomes in Apple Orchards Are Influenced by the Type of Agricultural Management but Never Match the Complexity and Connectivity of a Semi-natural Benchmark
Authors: Hulsmans Eva , Peeters Gerrit , Honnay Olivier
Published: February 2022

Conversion of natural ecosystems into agricultural land may strongly affect the soil microbiome and the functioning of the soil ecosystem. Alternative farming systems, such as organic farming, have therefore been advocated to reduce this impact, yet the outcomes of different agricultural management regimes often remain ambiguous and their evaluations mostly lack a proper more natural benchmark. We used high-throughput amplicon sequencing, linear models, redundancy analyses, and co-occurrence network analyses to investigate the effect of organic and integrated pest management (IPM) on soil fungal and bacterial communities in both the crop and drive rows of apple orchards in Belgium, and we included semi-natural grasslands as a benchmark. Fungi were strongly influenced by agricultural management, with lower diversity indices and distinct communities in IPM compared to organic orchards, whereas IPM orchards had a higher AMF abundance and the most complex and connected fungal communities. Bacterial diversity indices, community composition, and functional groups were less affected by management, with only a higher network connectivity and abundance of keystone taxa in organic drive rows. On the other hand, none of the agricultural soil microbiomes matched the complexity and connectedness of our semi-natural benchmark, demonstrating that even more nature-friendly agricultural management practices strongly affect the soil microbiome and highlighting the essential role of (semi-)natural systems as a harbor of robust and functionally diverse fungal and bacterial communities.
4-Methoxydalbergione Inhibits Bladder Cancer Cell Growth via Inducing Autophagy and Inhibiting Akt/ERK Signaling Pathway
Authors: Du Haifang , Tao Ting , Xu Simeng , Xu Changqiong , Li Shan , Su Qiongli , Yan Jing , Liu Bo , Li Ran
Published: February 2022

Bladder cancer (BC) ranks the fourth in incidence in cancers of men and is a common malignant tumor in women. 4-Methoxydalbergione (4MOD), which is purified from Dalbergia sissoo Roxb, has been shown to have anticancer capacity for osteosarcoma and astroglioma. The role of 4MOD in bladder cancer has not been investigated. This study aims to evaluate the anticancer effect of 4MOD in BC cells and its possible mechanisms. The two human bladder cancer cell lines J82 and UMUC3 were used to evaluate the proliferation inhibitory effect of 4MOD by CCK8 and clonogenic assays. The migratory and invasive ability of tumor cells was examined by scratch test and transwell assay. Apoptosis was detected by flow cytometry and TUNEL assays. The autophagy-related molecules including Beclin-1 and LC3 were examined by Western blotting analysis. Furthermore, the RT-PCR was used to detect the mRNA expression of LC3. 4MOD repressed cell proliferation, migration, invasion and induced cell apoptosis in a concentration-dependent manner. The IC50 values of J82 and UMUC3 were 8.17 and 14.50 μM respectively. The mRNA and protein expression ratio of light chain 3-II (LC3-II)/LC3-I and the protein expression of Beclin-1 were increased when the BC cells were treated with 4MOD. The treatment of 4MOD attenuated the phosphorylation of Akt and ERK in the BC cells. We revealed that the 4MOD inhibits BC cells growth by inducing autophagy and inhibiting Akt/ERK signaling pathway. Our study provides new insights into the mechanism by which 4MOD weakens the proliferation of BC cells. This study demonstrates that 4MOD provided a lead compound for the development of novel compound with potent anticancer effect on BC cells.
Integrating lncRNAs and mRNAs Expression Profiles in Penicillin-Induced Persistent Chlamydial Infection in HeLa Cells
Authors: Huang Xiaobao , Liufu Qian , Xu Rui , Chen Xiaohong , Liu Mingna , Han Jiande , Guan Hongyu , Ma Chunguang
Published: February 2022

Chlamydia trachomatis (C. trachomatis) is a major etiological agent of sexually transmitted infection. Some stressing conditions can result in persistent chlamydial infection, which is thought to be associated with severe complications including ectopic pregnancy and tubal factor infertility. Long noncoding RNAs (lncRNAs) have been identified as key modulators in many biological processes. Nevertheless, the role of lncRNAs in persistent chlamydial infection is still unclear. In this study, we used lncRNA and mRNA microarray to identify the global lncRNAs and mRNAs expression in penicillin-induced persistent chlamydial infection in HeLa cells as well as the control group (HeLa cells without C. trachomatis infection). Among 1005 differentially expressed lncRNAs, 585 lncRNAs were upregulated and 420 downregulated in persistent chlamydial infection, while 410 mRNAs were identified to express differentially, of which 113 mRNAs were upregulated and 297 downregulated. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis with differentially expressed genes were performed. We then constructed the lncRNA-miRNA-mRNA competing endogenous RNAs (ceRNAs) network. Four mRNAs were validated to be changed by quantitative real-time PCR which were correlated with the microarray result. Integration of protein-protein interaction network was constructed and hub genes were identified. These findings provide a new perspective on the molecular mechanisms of penicillin-induced persistent chlamydial infection.
Comparative Efficacy of Multiple Therapies for the Treatment of Patients With Subthreshold Depression: A Systematic Review and Network Meta-Analysis
Authors: Jiang Xiumin , Luo Yongxin , Chen Yiwen , Yan Jinglan , Xia Yucen , Yao Lin , Wang Xiaotong , He Su , Wang Feixue , Wang Taiyi , Chen Yongjun
Published: February 2022

Graphical Abstract

Graphical abstract of the network meta-analysis. Note: CES-D, Center for Epidemiologic Studies Depression Scale; BDI, Beck Depression Inventory Scale; PHQ-9, the nine-Item Patient Health Questionnaire; K6, Kessler Screening Scale for Psychological Distress; SUCRA, surface area under the cumulative ranking curves.