bluuebunny/crossref_metadata_2025 huggingface dataset:
Analisis Du Pont System dalam menilai kinerja keuangan pada sektor makanan dan minuman di BEI Periode 2016-2020
Authors: Zahra Al Az , Febrianty Febrianty
Published: July 2022

Food and beverage sub-sector companies have stock prices and stock profits during the period 2016 to 2020 indicating instability or fluctuations between income and stock prices in each period, the condition that occurs is that the company experiences an increase in profits but the stock price falls, but there are companies that have increased stock prices but stock profits have decreased. The purpose of this study is to determine the company's financial performance in the food and beverage sub-sector using the du pont system method on the Indonesia Stock Exchange for the past five years (Period 2016 – 2020). The method used is du pont system analysis with a quantitative approach that includes calculating net profit margin (NPM), total asset turnover (TATO), equity multiplier (EM), return on investment (ROI), and return on equity (ROE). Based on the results of the research conducted, it was concluded that the financial performance of 5 companies in the food and beverage sub-sector studied for the period 2016-2020 company PT Multi Bintang Indonesia, Tbk which has the highest ROE value with excellent financial performance, where the level of sales in each year has increased continuously.
Pengaruh Kewajiban Moral Dan Digitalisasi Layanan Pajak Terhadap Kepatuhan Wajib Pajak Dengan Nasionalisme Sebagai Pemoderasi
Authors: Tambun Sihar , Ananda Nurul Aulia
Published: July 2022

This study aims to examine the effect of moral obligation and digitization of tax services on taxpayer compliance with nationalism as a moderator. The population used in this study are taxpayers who understand the process of reporting and paying taxes. The number of data is 100 respondents who are taken through a questionnaire using partial least squares (PLS) data analysis. Based on statistical tests, the results of the study show that Moral Obligations have no significant effect on taxpayer compliance. Digitization of Tax Services has a significant effect on Taxpayer Compliance. Nationalism has no significant effect on taxpayer compliance. Moral Obligations to Taxpayer Compliance if moderated by Nationalism have a significant effect. Digitizing Tax Services on Taxpayer Compliance if moderated with Nationalism does not have a significant effect
Pengaruh Profitabilitas (ROA), Likuiditas (AKO), Ukuran Perusahaan (SIZE), dan Leverage (LTDER) terhadap Nilai Perusahaan
Authors: Natalie Vannessa , Lisiantara G. Anggana
Published: July 2022

Firm value is the investor's perception of a company related to stock prices. High company value will make the market not only believe in the company's current performance, but also on its future prospects. In the preparation of this study, the aim was to examine and analyze the effect of profitability, liquidity, company size, and leverage on firm value in property and real estate companies listed on the Indonesia Stock Exchange (IDX) for the 2017-2021 period. This study uses a population of all property and real estate companies that have been listed on the Indonesia Stock Exchange (IDX) in the last five periods, namely 2017-2021. The sample selection method used in this study was a purposive sampling technique with several selected criteria, so as to obtain a sample of 105 companies. This study uses secondary data in the form of numbers that are processed into a statistical measurement scale, so it is called secondary data. The data analysis technique used is multiple linear regression analysis. The results of this study indicate that profitability (ROA) and firm size (SIZE) have no effect on firm value, liquidity (AKO) has a positive and significant effect on firm value, while leverage (LTDER)  has a negative and significant effect on firm value.
Penerapan prosedur pengajuan dan penyelesaian pengurangan pensiunan Pajak Bumi dan Bangunan terhadap Penerimaan Asli Daerah pada BPPD Wilayah UPT Tengah Kota Bandung
Authors: Septianti Luci , Purnamasari Dyah
Published: July 2022

In applying the procedure for submitting and completing the reduction of the Land and Building tax pension on the original local revenue at the BPPD in the Central UPT area of ??Bandung. The formulation of the problems studied in this study are 1. How is the application of the Land and Building Tax pension application at the BPPD in the Central UPT area of ??Bandung City. 2. How is the settlement effort in granting a reduction in Land and Building Tax pensions at the BPPD in the Central UPT area of ??Bandung. The purpose of this study is to find out how to submit a reduction and what requirements are needed in an application for a reduction in PBB and what are the obstacles and how to resolve the reduction in PBB against local revenue at the BPPD in the Central UPT area of ??Bandung City. The method used in this study is qualitative, namely research procedures that use descriptive written or spoken words that are observed. This research is located at the BPPD Office in the UPT Central Bandung area. By conducting interviews, observing and studying related documents at the BPPD in the Central Bandung UPT area, it can be concluded that the functions involved, the forms used and the application of the submission procedures are still not in accordance with SPIP such as officers receiving incomplete application files. Therefore, socialization is very necessary to provide information to taxpayers regarding the procedures and what requirements are needed in the submission and settlement of the PBB pension reduction.
Analogias relacionadas ao conteúdo-conceitual quantidade de matéria em livros didáticos de Química do Ensino Médio
Authors: Barbosa Everton Koloche Mendes , Romero Adriano Lopes , Monteiro Paula Cavalcante
Published: July 2022

O raciocínio analógico tem sido amplamente utilizado para o desenvolvimento de conceitos científicos, principalmente no século XIX. No âmbito do ensino de Química, a linguagem analógica tem sido utilizada como um recurso para facilitar o ensino e aprendizagem de conceitos químicos abstratos. No entanto, a literatura especializada indica que o uso de analogias, caso não seja realizada de forma adequada, pode gerar obstáculos epistemológicos. Nesse contexto, o presente trabalho avaliou o uso de analogias utilizadas para abordar o conteúdo escolar quantidade de matéria em livros didáticos de Química publicados em diferentes períodos. A partir do estudo comparativo entre as obras, observamos avanços na qualidade das analogias utilizadas na explicação do conteúdo-conceitual quantidade de matéria e sua unidade, o mol. Os resultados evidenciaram que esse recurso de linguagem configura um ótimo instrumento para a construção do conhecimento, mas que, se empregado de maneira não sistematizada, as analogias podem causar distorções no entendimento dos conteúdos científicos. O estudo concede uma discussão de teor didático a partir da qual, docentes possam se instrumentalizar quanto ao uso adequado e à importância das relações analógicas no letramento científico.
Reproductive biology and population parameters of commercially important Characiformes from the Araguari River, state of Amapá, Brazil
Authors: Araujo Gabriel Fauro de , Souza Luiza Prestes de , Oliveira Marcos Sidney Brito de , Soares Maria Gercilia Mota
Published: July 2022

The present study aimed to estimate the length-weight relationship, relative condition factor (Kn), gonadosomatic index (GSI) and mean length at first maturity (L50) for 11 fish species serving as a subsidy for fisheries management of the Upper and Middle Araguari River. Samplings were conducted in the 2011-2014 period, with experimental fisheries and landing data; fish were measured (cm), sexed, and total weight (g) and gonad weight (g) were recorded. The length-weight relationship for all species had r2 above 0.76, indicating isometric growth for A. inermis, A. falcatus, Charax sp., L. melanosticus, L. maculatus, S. eingemani. On the other hand, H. aimara, B. cuvieri, M. asterias, M. romboidalis and M. ternetzi showed allometric growth, the first two species with positive growth and the rest, negative. The combination of the relative condition factor (Kn) and the gonadosomatic index (GSI) was a good indicator of the reproductive period for A. inermis, A. falcatus, B. cuvieri and M. ternetzi. The estimated L50values presented a minimum value of 12 cm for M. asterias, and a maximum of 28.6 cm for H. aimara. This study is of paramount importance for fisheries management and conservation of the studied area, especially as it is the first study for some species in the region.
Expanding the genomes insight of Streptococcus thermophilus phages through a multifaceted approach
Authors: Batalha Laís S. , Vidigal Pedro Marcus P. , Gontijo Marco Túllio P. , Eller Monique R.
Published: July 2022

Viruses have complex evolutionary relationships, and several strategies have been used in an attempt to classify the phages that infect S. thermophilus. In this study, we used a wide range of complementary methods, including comparative genomics, core genome analysis, and signature genes phylogenetics, to show that the S. thermophilus phages are organized into 142 species and five genera (three of them new) and that due to their genetic diversity, the classification at family level varies according to the classification criteria used. No significantly conserved genes were identified among the 183 genomes evaluated. However, the genes encoding holin protein were conserved in more than 95% of genomes. The holins analysis suggests that at least two α-helix are required for protein function within S. thermophilus phages. This study expanded the of knowledge about the genetic diversity and evolution of streptococcal phages, both fundamental to promoting control strategies and minimizing failures in milk fermentation processes.
Qualidade de vida de mulheres no climatério na atenção básica de saúde
Authors: Melo Filho Jean Carlos Leal Carvalho de , Lopes Ione Maria Ribeiro Soares
Published: July 2022

Analisar os sintomas e a qualidade de vida de mulheres no climatério atendidas na atenção básica de saúde. Estudo analítico, transversal e quantitativo, realizado em Unidade Básica de Saúde da zona rural do município de Buriti dos Montes-PI. A amostra foi baseada no número de mulheres cadastradas na UBS com idade de 40 a 65 anos. Foram excluídas no estudo mulheres ooforectomizadas ou em uso de Terapia de Reposição Hormonal. Para a coleta de dados foram utilizados um questionário abordando a caracterização socioeconômica das participantes da pesquisa e outro questionário abordando a qualidade de vida das mulheres no climatério (Women’s Health Questionnare). A pesquisa seguiu as normas de ética em pesquisa relacionadas a seres humanos. A idade média das mulheres foi de 55 anos, casadas, multíparas, pardas, com renda familiar inferior a 1 salário-mínimo. Apresentavam sobrepeso e a maioria apresentava risco altíssimo para complicações metabólicas. A idade média da menarca foi 13,15 anos e da menopausa 46,51 anos. A maioria das participantes da pesquisa fazia uso de alguma medicação com maior incidência de anti-hipertensivos, não realizavam atividade física e eram sexualmente ativas. As queixas que mais afetaram as participantes foram dores nas costas e nos membros, fogachos e suores noturnos. O domínio que mais comprometeu a qualidade de vida das mulheres no climatério foram os sintomas vasomotores. Concluiu-se que a qualidade de vida das mulheres no climatério é afetada pela síndrome do climatério.
Comparative visual and DNA-based diet assessment extends the prey spectrum of polar cod Boreogadus saida
Authors: Maes SM , Schaafsma FL , Christiansen H , Hellemans B , Lucassen M , Mark FC , Flores H , Volckaert FAM
Published: August 2022

The Arctic marine ecosystem is changing fast due to climate change, emphasizing the need for solid ecological baselines and monitoring. The polar cod Boreogadus saida functions as a key species in the Arctic marine food web. We investigated the stomach contents of polar cod from the northern Barents Sea using DNA metabarcoding with the mitochondrial cytochrome c oxidase I gene in parallel with classical visual analysis. Arctic amphipods and krill dominated the diet in both methods. Yet, metabarcoding allowed for the identification of digested and unidentifiable prey and provided higher taxonomic resolution, revealing new and undiscovered prey items of polar cod in the area. Furthermore, molecular results suggest a higher importance of barnacles and fish (presumably eggs and pelagic larvae) in the diet than previously recorded. Parasites and, in 6 cases, other prey items were only visually identified, demonstrating the complementary nature of both approaches. The presence of temperate and boreal prey species such as northern krill and (early life stages of) European flounder and European plaice illustrates the advection of boreal taxa into the polar region or may be indicative of ongoing borealisation in the Barents Sea. We show that a combination of visual analysis and metabarcoding provides complementary and semi-quantitative dietary information and integrative insights to monitor changing marine food webs.
MCC-134, a blocker of mitochondrial and opener of sarcolemmal ATP-sensitive K+ channels, abrogates cardioprotective effects of chronic hypoxia.
Authors: Kolář F , Neckář J , Ošťádal B
Published: August 2022

We examined the effect of MCC-134, a novel inhibitor of mitochondrial ATP-sensitive K+ (mitoKATP) channels and activator of sarcolemmal ATP-sensitive K+ (sarcKATP) channels, on cardioprotection conferred by adaptation to chronic hypoxia. Adult male Wistar rats were exposed to intermittent hypobaric hypoxia (7000 m, 8 h/day, 5-6 weeks) and susceptibility of their hearts to ventricular arrhythmias and myocardial infarction was evaluated in anesthetized open-chest animals subjected to 20-min coronary artery occlusion and 3-h reperfusion on the day after the last hypoxic exposure. MCC-134 was administered intravenously 10 min before ischemia and 5 min before reperfusion in a total dose of 0.3 mg/kg or 3 mg/kg divided into two equal boluses. The infarct size (tetrazolium staining) was reduced from 59.2±4.4 % of the area at risk in normoxic controls to 43.2±3.3 % in the chronically hypoxic group. Chronic hypoxia decreased the reperfusion arrhythmia score from 2.4±0.5 in normoxic animals to 0.7±0.5. Both doses of MCC-134 completely abolished the antiarrhythmic protection (score 2.4±0.7 and 2.5±0.5, respectively) but only the high dose blocked the infarct size-limiting effect of chronic hypoxia (54.2±3.7 %). MCC-134 had no effect in the normoxic group. These results support the view that the opening of mitoKATP channels but not sarcKATP channels plays a crucial role in the mechanism by which chronic hypoxia improves cardiac tolerance to ischemia/reperfusion injury.
Markers of oxidative stress in diabetic mothers and their infants during delivery.
Authors: Rajdl D , Racek J , Steinerová A , Novotný Z , Stožický F , Trefil L , Siala K
Published: August 2022

Oxidative stress is probably a pathophysiological process leading to disadvantageous outcomes in diabetic pregnancies. We aimed to map a complex of potential markers of oxidative stress in this condition. Diabetic mothers had significantly higher concentrations of thiobarbituric acid reactive substances in the plasma [TBARS] both before (p<0.0001) and after (p<0.001) delivery and also their newborns showed higher values of TBARS (p<0.0001) in comparison with the control group. Diabetic mothers also showed lower concentrations of reduced glutathione in erythrocytes [GSH] both before (p<0.05) and after (p<0.01) delivery and their infants also had lower levels of GSH (p<0.0001). We found a lower total antioxidative capacity of plasma [AOC] before delivery (p<0.05) in the diabetic group in comparison with the control group. Newborns of diabetic mothers had higher plasmatic concentrations of apolipoproteine B [apo B] (p<0.05), higher erythrocyte glutathione peroxidase [GPx] activity (p<0.05) and lower pH (p<0.001) in the umbilical cord blood, when compared with infants of control non-diabetic mothers. We conclude that pregestational and gestational diabetes mellitus represent increased oxidative stress for both mother and her infant. TBARS in plasma are a valuable marker of oxidative stress in this condition. Disruption of glutathione peroxidase/glutathione pattern can be involved in pathophysiology of enhanced oxidative stress in diabetic pregnancies.
HAKIKAT, TUJUAN DAN KARAKTERISTIK PEMBELAJARAN IPS YANG BERMAKNA PADA PESERTA DIDIK SEKOLAH DASAR
Authors: Hopeman Teofilus Ardian , Hidayah Nur , Anggraeni Winda Arum
Published: July 2022

Pada hakikatnya pembelajaran IPS sangat penting diajarkan kepada siswa sejak mereka menempuh pendidikan dasar. Hal ini dapat terlihat dari banyaknya siswa yang masih belum memahami sepenuhnya setiap materi yang diajarkan pada pelajaran IPS Pada era revolusi 4.0 diharapkan pendidik dapat menfasilitasi peserta didik untuk dapat berpikir kritis terhadap masalah sosial dan kehidupansosial, kreatif dalam menanggapi hal-hal yang berhubungan dengan kehidupan sosial, pendidik mampu mengarahkan peserta didik untuk berdiskusi terhadap sesama dan juga melakukan kerja sama untuk menanggapi hal-hal dalam kehidupan bermasyarakat. Pembelajaran IPS pada tingkat sekolah dasar (SD) harus dibelajarkan kepeserta didik secara kontruktivis.terdapat 5 (lima) metode yang dapat diajarkan pada pembelajaran IPS antara lain cooperative based learning, design based learning, inquiry based learning, project based learning, dan problem based learning. Metode yang digunakan pada penilitian ini berupa kajian pustaka.
Pemikiran Pendidikan Islam Syekh Ahmad al-Qushashi dan Relevansinya di Era Modern
Authors: Fathoni Hanif
Published: July 2022

Islamic education of Indonesia cannot be separated from the role of previous middle eastern scholars. Sheikh Ahmad al-Qushāshī is one of the middle eastern scholars who influenced previously the thinking of Indonesian scholars, whose students took many roles in Indonesian history. Some of the problems discussed in this study are the objectives, methods, educational curriculum and patterns of teacher-student interaction according to Sheikh Ahmad al-Qushāshī and their relevance to modern education in Indonesia. This research is a library research with analytical descriptive method, with several literature sources examined such as as-Simth al-Majid, Manżūmah al-Tawhīd, and other sources. The data analysis technique used is content analysis initiated by Shelley and Krippendorff. The results of research on the educational thinking of al-Qushāsh are briefly as follows: the purpose of education according to al-Qushāsh is to unite God, and become a pious servant. The educational curriculum is a curriculum based on monotheism which is divided into common, special and very special. The al-Qushāshī curriculum approach has an integration pattern between exoteric and esoteric sciences. The method of al-Qushāshī education is the exemplary method, bai'at-talqīn, al-Ŝuhbah and al-ta'dīb, taslīm, and Ilbās. The pattern of teacher-student interaction has a familial pattern of interaction (teachers act as parents, educators, and student guides), so that his thoughts are quite relevant to the modern era.
Approach to the Treatment of Pediatric Dystonia
Authors: Gorodetsky Carolina , Fasano Alfonso
Published: August 2022

Dystonia is the most common movement disorder in the pediatric population. It can affect normal motor development and cause significant motor disability. The treatment of pediatric dystonia can be very challenging as many children tend to be refractory to standard pharmacological interventions. Pharmacological treatment remains the first-line approach in pediatric dystonia. However, despite the widespread use of different ani-dystonia medications, the literature is limited to small clinical studies, case reports, and experts’ opinions. Botulinum neurotoxin (BoNT) is a well-established treatment in adults with focal and segmental dystonia. Despite the widespread use of BoNT in adult dystonia the data to support its use in children is limited with the majority extrapolated from the spasticity literature. For the last 2 decades, deep brain stimulation (DBS) has been used for a wide variety of dystonic conditions in adults and children. DBS gained increased popularity in the pediatric population because of the dramatic positive outcomes reported in some forms of genetic dystonia and the subsequent consensus that DBS is generally safe and effective. This review summarizes the available evidence supporting the efficacy and safety of pharmacological treatment, BoNT, and DBS in pediatric dystonia and provides practical frameworks for the adoption of these modalities.
A nomogram for clinical estimation of acute biliary pancreatitis risk among patients with symptomatic gallstones: A retrospective case-control study
Authors: Guo Xiaoyu , Li Yilong , Lin Hui , Cheng Long , Huang Zijian , Lin Zhitao , Mao Ning , Sun Bei , Wang Gang , Tang Qiushi
Published: August 2022

Background/Purpose

Currently, there are no effective tools to accurately assess acute biliary pancreatitis (ABP) risk in patients with gallstones. This study aimed to develop an ABP risk nomogram in patients with symptomatic gallstones.

Methods

We conducted a retrospective nested case-control study and data on 816 conservatively treated patients with symptomatic gallstones admitted to The First Affiliated Hospital of Harbin Medical University between January 6, 2007 and January 22, 2016 were retrospectively collected. We conducted a propensity-score matched (PSM) analysis based on follow-up time in a ratio of 1:4 between ABP group (n=65) and non-ABP group (n=260). These matched patients were randomly divided into study cohort (n=229) and validation cohort (n=96) according to a ratio of 7:3. In the study cohort, independent risk factors for ABP occurrence identified using Cox regression were included in nomogram. Nomogram performance and discrimination were assessed using the concordance index (C-index), area under the curve (AUC), calibration curve, decision curve analysis (DCA) and clinical impact curve (CIC). The model was also validated in the validation cohort.

Results

Nomogram was based on 7 independent risk factors: age, diabetes history, gallbladder wall thickness, gallstone diameter, coexisting common bile duct (CBD) stones, direct bilirubin (DBIL), and white blood cell count (WBC). The C-index of nomogram was 0.888, and the 10-year AUCs of nomogram was 0.955. In the validation cohort, nomogram still had good discrimination (C-index, 0.857; 10-year AUC, 0.814). The calibration curve showed good homogeneity between the prediction by nomogram and the actual observation. DCA and CIC demonstrated that nomogram was clinically useful.

Conclusions

The ABP risk nomogram incorporating 7 features is useful to predict ABP risk in symptomatic gallstone patients.
Dysregulated autophagy-related genes in septic cardiomyopathy: Comprehensive bioinformatics analysis based on the human transcriptomes and experimental validation
Authors: Zou Hua-Xi , Qiu Bai-Quan , Zhang Ze-Yu , Hu Tie , Wan Li , Liu Ji-Chun , Huang Huang , Lai Song-Qing
Published: August 2022

Septic cardiomyopathy (SCM) is severe organ dysfunction caused by sepsis that is associated with poor prognosis, and its pathobiological mechanisms remain unclear. Autophagy is a biological process that has recently been focused on SCM, yet the current understanding of the role of dysregulated autophagy in the pathogenesis of SCM remains limited and uncertain. Exploring the molecular mechanisms of disease based on the transcriptomes of human pathological samples may bring the closest insights. In this study, we analyzed the differential expression of autophagy-related genes in SCM based on the transcriptomes of human septic hearts, and further explored their potential crosstalk and functional pathways. Key functional module and hub genes were identified by constructing a protein–protein interaction network. Eight key genes (CCL2, MYC, TP53, SOD2, HIF1A, CTNNB1, CAT, and ADIPOQ) that regulate autophagy in SCM were identified after validation in a lipopolysaccharide (LPS)-induced H9c2 cardiomyoblast injury model, as well as the autophagic characteristic features. Furthermore, we found that key genes were associated with abnormal immune infiltration in septic hearts and have the potential to serve as biomarkers. Finally, we predicted drugs that may play a protective role in SCM by regulating autophagy based on our results. Our study provides evidence and new insights into the role of autophagy in SCM based on human septic heart transcriptomes, which would be of great benefit to reveal the molecular pathological mechanisms and explore the diagnostic and therapeutic targets for SCM.
D-Dimer Is Associated With Coronary Microvascular Dysfunction in Patients With Non-obstructive Coronary Artery Disease and Preserved Ejection Fraction
Authors: Lin Yan , Hu Xiangming , Wang Weimian , Yu Bingyan , Zhou Langping , Zhou Yingling , Li Guang , Dong Haojian
Published: August 2022

Background

Coronary microvascular dysfunction (CMVD), an important etiology of ischemic heart disease, has been widely studied. D-dimer is a simple indicator of microthrombosis and inflammation. However, whether an increase in D-dimer is related to CMVD is still unclear.

Materials and Methods

This retrospective study consecutively enrolled patients with myocardial ischemia and excluded those with obstructive coronary artery. D-dimer was measured at admission and the TIMI myocardial perfusion grade (TMPG) was used to distinguish CMVD. Patients were divided into the two groups according to whether the D-dimer was elevated (>500 ng/ml). Logistic models and restricted cubic splines were used to explore the relationship between elevated D-dimer and CMVD.

Results

A total of 377 patients were eventually enrolled in this study. Of these, 94 (24.9%) patients with CMVD had older age and higher D-dimer levels than those without CMVD. After full adjustment for other potential clinical risk factors, patients with high D-dimer levels (>500 ng/ml) had a 1.89-times (95% CI: 1.09–3.27) higher risk of CMVD than patients with low D-dimer levels. A non-linear relationship was found between concentrations of D-dimer and CMVD. With increased D-dimer level, the incidence of CMVD increased and then remained at a high level. Stratified analysis was performed and showed similar results.

Conclusion

Elevated D-dimer level is associated with the incidence of CMVD and potentially serves as a simple biomarker to facilitate the diagnosis of CMVD for patients with angina.
Effect of Rhizoma Drynariae on differential gene expression in ovariectomized rats with osteoporosis based on transcriptome sequencing
Authors: Su Hui , Xue Haipeng , Gao Shang , Yan Binghan , Wang Ruochong , Tan Guoqing , Xu Zhanwang , Zeng Lingfeng
Published: August 2022

Osteoporosis is increasingly becoming a serious problem affecting the quality of life of the older population. Several experimental studies have shown that Chinese medicine has a definite effect on improving osteoporosis. Based on transcriptome sequencing, we analyzed the differential gene expression and mechanism of the related signaling pathways. Fifteen rats were randomly divided into an experimental group, a model group, and a sham surgery group. The rat model for menopausal osteoporosis was established using an ovariectomy method. One week after modeling, the experimental group was administered(intragastric administration)8.1 g/kg of Rhizoma drynariae, whereas the model and sham groups received 0.9% saline solution twice daily for 12 weeks. Subsequently, the rats were sacrificed, and the left femur of each group was removed for computerized tomography testing, while right femurs were used for hematoxylin and eosin staining. High-throughput RNA sequencing and functional and pathway enrichment analyses were performed. Comparing the gene expression between the experimental and model groups, 149 differential genes were identified, of which 44 were downregulated and 105 were upregulated. The criteria for statistical significance were |log2 Fold Change| > 1 and P < 0.05. Gene ontology analysis showed that the differentially expressed genes were enriched in cell component terms such as cell part and outer cell membrane part, and the genes were associated with cell process, biological regulation, metabolic processes, DNA transcription, and catalytic activity. Enrichment analysis of Kyoto Encyclopedia of Genes and Genomes pathways showed significantly enriched pathways associated with systemic lupus erythematosus, herpes simplex infection, circadian rhythm, vascular smooth muscle contraction, the AGE-RAGE signaling pathway in diabetic complications, and the TNF, Apelin, and Ras signaling pathways. Our results revealed that the Npas2, Dbp, Rt1, Arntl, Grem2, H2bc9, LOC501233, Pla2g2c, Hpgd, Pde6c, and Dner genes, and the circadian rhythm, lipid metabolism, inflammatory signaling pathway, and immune pathways may be the key targets and pathways for traditional Chinese medicine therapy of Rhizoma Drynariae in osteoporosis.
Hydroxychloroquine overcomes cabergoline resistance in a patient with Lactotroph Pituitary neuroendocrine tumor: a case report
Authors: Lin Shaojian , Han Changxi , Lou Xiaohui , Wu Zhe Bao
Published: August 2022

Objective

A 22-year-old man complaining erectile dysfunction underwent transsphenoidal surgery for a 2.7 cm sellar mass with total resection and was confirmed at pathology to have a lactotroph pituitary neuroendocrine tumor (PiNET). Postoperatively, the patient’s PRL remained at high level and therefore accepted high-dose dopamine receptor agonist (DA) therapy. After over 3 months of bromocriptine (BRC) (15mg/day) and over 3 years of cabergoline (CAB) (3mg/week) therapy, the patient’s prolactin (PRL) never achieved long-term normalization. He was diagnosed with DA-resistant lactotroph PitNET.

Method

In this study, the patient was given hydroxychloroquine (HCQ) (200 mg/d) and CAB (3 mg/w) in combination for four months. His PRL level was tested by blood test every month.

Results

Taking the combination therapy of HCQ and CAB, the patient’s uncontrolled PRL level was normalized within one month and was maintained at the normal level thereafter. Pituitary magnetic resonance imaging (MRI) images with enhancement showed no recurrence. The patient also regained normal sexual function.

Discussion

This is the first report on the combination of HCQ with CAB for the effective treatment of DA-resistant lactotroph pituitary neuroendocrine tumor in a patient, which might provide a novel treatment strategy for clinical management.
Responses of regulatory and effector T-cells to low-dose interleukin-2 differ depending on the immune environment after allogeneic stem cell transplantation
Authors: Meguri Yusuke , Asano Takeru , Yoshioka Takanori , Iwamoto Miki , Ikegawa Shuntaro , Sugiura Hiroyuki , Kishi Yuriko , Nakamura Makoto , Sando Yasuhisa , Kondo Takumi , Sumii Yuichi , Maeda Yoshinobu , Matsuoka Ken-ichi
Published: August 2022

CD4+Foxp3+regulatory T cells (Tregs) play a central role in the maintenance of immune tolerance after allogeneic hematopoietic stem cell transplantation (HSCT). Tregs promptly respond to low concentrations of IL-2 through the constitutive expression of high-affinity IL-2 receptors. It has been reported that low-dose IL-2 therapy increased circulating Tregs and improved clinical symptoms of chronic GVHD. Clinical studies of IL-2 therapy so far have mainly targeted patients in the chronic phase of transplantation when acute immune responses has subsided. However, the biological and clinical effects of exogenous IL-2 in an acute immune environment have not been well investigated. In the current study, we investigated the impact of exogenous IL-2 therapy on the post-transplant homeostasis of T cell subsets which influence the balance between GVHD and GVL in the acute phase, by setting the various immune environments early after HSCT in murine model. We initially found that 5,000 IU of IL-2 was enough to induce the active proliferation of Treg without influencing other conventional T cells (Tcons) when administered to normal mice. However, activated Tcons showed the response to the same dose of IL-2 in recipients after allogeneic HSCT. In a mild inflammatory environment within a threshold, exogenous IL-2 could effectively modulate Treg homeostasis with just limited influence to activated T cells, which resulted in an efficient GVHD suppression. In contrast, in a severely inflammatory environment, exogenous IL-2 enhanced activated T cells rather than Tregs, which resulted in the exacerbation of GVHD. Of interest, in an immune-tolerant state after transplant, exogenous IL-2 triggered effector T-cells to exert an anti-tumor effect with maintaining GVHD suppression. These data suggested that the responses of Tregs and effector T cells to exogenous IL-2 differ depending on the immune environment in the host, and the mutual balance of the response to IL-2 between T-cell subsets modulates GVHD and GVL after HSCT. Our findings may provide useful information in the optimization of IL-2 therapy, which may be personalized for each patient having different immune status.
Gut microbiota in systemic lupus erythematosus patients and lupus mouse model: a cross species comparative analysis for biomarker discovery
Authors: Toumi Eya , Goutorbe Benoit , Plauzolles Anne , Bonnet Marion , Mezouar Soraya , Militello Muriel , Mege Jean-Louis , Chiche Laurent , Halfon Philippe
Published: August 2022

An increasing number of studies have provided strong evidence that gut microbiota interact with the immune system and stimulate various mechanisms involved in the pathogenesis of auto-immune diseases such as Systemic Lupus Erythematosus (SLE). Indeed, gut microbiota could be a source of diagnostic and prognostic biomarkers but also hold the promise to discover novel therapeutic strategies. Thus far, specific SLE microbial signatures have not yet been clearly identified with alteration patterns that may vary between human and animal studies. In this study, a comparative analysis of a clinically well-characterized cohort of adult patients with SLE showed reduced biodiversity, a lower Firmicutes/Bacteroidetes (F/B) ratio, and six differentially abundant taxa compared with healthy controls. An unsupervised clustering of patients with SLE patients identified a subgroup of patients with a stronger alteration of their gut microbiota. Interestingly, this clustering was strongly correlated with the disease activity assessed with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score (p = 0.03, odd ratio = 15) and the identification of specific alterations involving the F/B ratio and some different taxa. Then, the gut microbiota of pristane-induced lupus and control mice were analyzed for comparison with our human data. Among the six differentially abundant taxa of the human disease signature, five were common with our murine model. Finally, an exhaustive cross-species comparison between our data and previous human and murine SLE studies revealed a core-set of gut microbiome species that might constitute biomarker panels relevant for future validation studies.
Shifting gears: Id3 enables recruitment of E proteins to new targets during T cell development and differentiation
Authors: Anderson Michele K.
Published: August 2022

Shifting levels of E proteins and Id factors are pivotal in T cell commitment and differentiation, both in the thymus and in the periphery. Id2 and Id3 are two different factors that prevent E proteins from binding to their target gene cis-regulatory sequences and inducing gene expression. Although they use the same mechanism to suppress E protein activity, Id2 and Id3 play very different roles in T cell development and CD4 T cell differentiation. Id2 imposes an irreversible choice in early T cell precursors between innate and adaptive lineages, which can be thought of as a railway switch that directs T cells down one path or another. By contrast, Id3 acts in a transient fashion downstream of extracellular signals such as T cell receptor (TCR) signaling. TCR-dependent Id3 upregulation results in the dislodging of E proteins from their target sites while chromatin remodeling occurs. After the cessation of Id3 expression, E proteins can reassemble in the context of a new genomic landscape and molecular context that allows induction of different E protein target genes. To describe this mode of action, we have developed the “Clutch” model of differentiation. In this model, Id3 upregulation in response to TCR signaling acts as a clutch that stops E protein activity (“clutch in”) long enough to allow shifting of the genomic landscape into a different “gear”, resulting in accessibility to different E protein target genes once Id3 decreases (“clutch out”) and E proteins can form new complexes on the DNA. While TCR signal strength and cytokine signaling play a role in both peripheral and thymic lineage decisions, the remodeling of chromatin and E protein target genes appears to be more heavily influenced by the cytokine milieu in the periphery, whereas the outcome of Id3 activity during T cell development in the thymus appears to depend more on the TCR signal strength. Thus, while the Clutch model applies to both CD4 T cell differentiation and T cell developmental transitions within the thymus, changes in chromatin accessibility are modulated by biased inputs in these different environments. New emerging technologies should enable a better understanding of the molecular events that happen during these transitions, and how they fit into the gene regulatory networks that drive T cell development and differentiation.
The cold-water coral Solenosmilia variabilis as a paleoceanographic archive for the reconstruction of intermediate water mass temperature variability on the Brazilian continental margin
Authors: Endress S. , Schleinkofer N. , Schmidt A. , Tracey D. , Frank N. , Raddatz J.
Published: August 2022

Recent oceanographic observations have identified significant changes of intermediate water masses characterized by increased temperatures, lowered pH and deoxygenation. In order to improve our understanding as to how these changes may impact deep-sea ecosystems one important strategy is to reconstruct past oceanic conditions. Here we examine the applicability of the scleractinian cold-water coral Solenosmilia variabilis as a marine archive for the reconstructions of past intermediate water mass temperatures by using Lithium (Li)/Magnesium (Mg) ratios. In particular, our study addresses 1) the calibration of Li/Mg ratios against in-situ temperature data, 2) the reconstruction of past intermediate water mass temperatures using scleractinian coral fossil samples from the Brazilian continental margin and 3) the identification of intraspecies variability within the coral microstructure. Results showed that Li/Mg ratios measured in the skeletons of S. variabilis fit into existing Li/Mg-T calibrations of other cold-water scleractinian. Furthermore, the coral microstructure exhibits interspecies variability of Li/Ca and Mg/Ca ratios were also similar to what has been observed in other cold-water scleractinian corals, suggesting a similar biomineralization control on the incorporation of Li and Mg into the skeleton. However, the Li/Mg based temperature reconstruction using fossil samples resulted in unexpectedly high variations >10°C, which might not be solely related to temperature variations of the intermediate water mass over the last 160 ka on the Brazilian continental margin. We speculate that such temperature variability may be caused by vertical movements of the aragonite saturation horizon and the associated seawater pH changes, which in turn influence the incorporation of Li and Mg into the coral skeleton. Based on these results it is recommended that future studies investigating past oceanic conditions need to consider the carbonate system parameters and how they might impact the mechanisms of Li and Mg being incorporated into skeletons of cold-water coral species such as S. variabilis.
Lionfish on the loose: Pterois invade shallow habitats in the tropical southwestern Atlantic
Authors: Soares Marcelo O. , Feitosa Caroline V. , Garcia Tatiane M. , Cottens Kelly Ferreira , Vinicius Bruno , Paiva Sandra Vieira , Duarte Oscar de Sousa , Gurjão Lívio Moreira , Silva Grasielle Dayse de Vasconcelos , Maia Rafaela Camargo , Previatto Diego M. , Carneiro Pedro B. M. , Cunha Edna , Amâncio Antonio Carlos , Sampaio Claudio L. S. , Ferreira Carlos E.L. , Pereira Pedro H.C. , Rocha Luiz A. , Tavares Tallita C. L. , Giarrizzo Tommaso
Published: August 2022

Lionfish (Pterois spp.) evolved in the Indo-Pacific with predators and prey and invaded regions (e.g., the Caribbean Sea and Mediterranean) where no such balance yet exists. In 2020, four lionfish were recorded on mesophotic reefs of the Amazon offshore Coast and Fernando de Noronha Archipelago. However, until now, there were no records of invasive lionfish in Brazilian nearshore waters or even such a high number of individuals. In this article, we report the continuing invasion process along the Brazilian Province by multiple sightings (72) of lionfish from March to May 2022 in estuaries, seagrass beds, and artificial and natural reefs across 240 km of the Brazilian coast. These are the first records of lionfish in coastal northeast Brazil and the shallowest records (1–16 m) from South Atlantic tropical waters. The largest simultaneous records of lionfish in breakwaters, fishing weirs, and marambaias (artificial reefs used as fishing grounds) on the Brazilian Northeastern coast indicate that these man-made structures are suitable habitats for this species. Most of the lionfish (58%) were recorded in artificial reefs and fishing weirs. Moreover, the detection of invasions in marginal reefs, estuaries, and two marine protected areas characterized by moderately turbid water and high sedimentation rates highlights the adaptability of the lionfish, making it extremely difficult for divers and fishers to capture them. We call for an urgent management plan considering that the invaded tropical region hosts a high level of endemism, and rare and/or cryptic taxa, which increases the risk of impacts since these are primary lionfish prey.
Predicting preterm birth through vaginal microbiota, cervical length, and WBC using a machine learning model
Authors: Park Sunwha , Moon Jeongsup , Kang Nayeon , Kim Young-Han , You Young-Ah , Kwon Eunjin , Ansari AbuZar , Hur Young Min , Park Taesung , Kim Young Ju
Published: August 2022

An association between the vaginal microbiome and preterm birth has been reported. However, in practice, it is difficult to predict premature birth using the microbiome because the vaginal microbial community varies highly among samples depending on the individual, and the prediction rate is very low. The purpose of this study was to select markers that improve predictive power through machine learning among various vaginal microbiota and develop a prediction algorithm with better predictive power that combines clinical information. As a multicenter case–control study with 150 Korean pregnant women with 54 preterm delivery group and 96 full-term delivery group, cervicovaginal fluid was collected from pregnant women during mid-pregnancy. Their demographic profiles (age, BMI, education level, and PTB history), white blood cell count, and cervical length were recorded, and the microbiome profiles of the cervicovaginal fluid were analyzed. The subjects were randomly divided into a training (n = 101) and a test set (n = 49) in a two-to-one ratio. When training ML models using selected markers, five-fold cross-validation was performed on the training set. A univariate analysis was performed to select markers using seven statistical tests, including the Wilcoxon rank-sum test. Using the selected markers, includingLactobacillusspp.,Gardnerella vaginalis,Ureaplasma parvum,Atopobium vaginae,Prevotella timonensis, andPeptoniphilus grossensis, machine learning models (logistic regression, random forest, extreme gradient boosting, support vector machine, and GUIDE) were used to build prediction models. The test area under the curve of the logistic regression model was 0.72 when it was trained with the 17 selected markers. When analyzed by combining white blood cell count and cervical length with the seven vaginal microbiome markers, the random forest model showed the highest test area under the curve of 0.84. The GUIDE, the single tree model, provided a more reasonable biological interpretation, using the 10 selected markers (A. vaginae,G. vaginalis,Lactobacillus crispatus,Lactobacillus fornicalis,Lactobacillus gasseri,Lactobacillus iners,Lactobacillus jensenii,Peptoniphilus grossensis,P. timonensis, andU. parvum), and the covariates produced a tree with a test area under the curve of 0.77. It was confirmed that the association with preterm birth increased whenP. timonensisandU. parvumincreased (AUC = 0.77), which could also be explained by the fact that as the number ofPeptoniphilus lacrimalisincreased, the association with preterm birth was high (AUC = 0.77). Our study demonstrates that several candidate bacteria could be used as potential predictors for preterm birth, and that the predictive rate can be increased through a machine learning model employing a combination of cervical length and white blood cell count information.
Endolysins against Streptococci as an antibiotic alternative
Authors: Wong Kuan Yee , Megat Mazhar Khair Megat Hamzah , Song Adelene Ai-Lian , Masarudin Mas Jaffri , Chong Chou Min , In Lionel Lian Aun , Teo Michelle Yee Mun
Published: August 2022

Multi-drug resistance has called for a race to uncover alternatives to existing antibiotics. Phage therapy is one of the explored alternatives, including the use of endolysins, which are phage-encoded peptidoglycan hydrolases responsible for bacterial lysis. Endolysins have been extensively researched in different fields, including medicine, food, and agricultural applications. While the target specificity of various endolysins varies greatly between species, this current review focuses specifically on streptococcal endolysins. Streptococcus spp. causes numerous infections, from the common strep throat to much more serious life-threatening infections such as pneumonia and meningitis. It is reported as a major crisis in various industries, causing systemic infections associated with high mortality and morbidity, as well as economic losses, especially in the agricultural industry. This review highlights the types of catalytic and cell wall-binding domains found in streptococcal endolysins and gives a comprehensive account of the lytic ability of both native and engineered streptococcal endolysins studied thus far, as well as its potential application across different industries. Finally, it gives an overview of the advantages and limitations of these enzyme-based antibiotics, which has caused the term enzybiotics to be conferred to it.