bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacognostic Potentials of Dried Powdered Seeds of Traditional Medicinal Plant Usteria guineensis used for the Treatment of Typhoid Fever in Sierra Leone
Authors: Koroma Lahai , Kamara L. M. , Frazer-Williams Ronnie , Jonathan Kpaka Augustine Kpaka
Published: February 2022

Pharmacognostic potentials and mineral analysis was carried out on the of dried powdered seeds of traditional medicinal plant Usteria guineensis used for the treatment of Typhoid fever in Sierra Leone. The results indicate the colour of the dried powdered seeds of the plant to be light yellow with fruit odour and had a bitter taste indicating that the powdered plant material contains alkaloids. The following reagents 1M NaOH (aq), 1M NaOH (alc.), Ammonia, 50% HCl, and 50% HNO3 exhibited fluorescent activities when added to portions of the dried powdered seeds of U. guineensis and viewed under UV Lamp. The plant organ investigated contained high contents of carbohydrates, alkaloids, flavonoids, proteins sterols/terpenes and tannins, saponins in the Ethanolic, methanol and aqueous extract during phytochemical screening. The detection of the above secondary plant metabolites supports the use of the plant in traditional medicine. Elemental analysis of the dried powdered seeds of U. guineensis using Niton XL3t GOLDD + Hand held X-ray Fluorescence (Thermo Fisher). The spectrum acquisition time was 480sec for the sample and the dead time was around 50% a total of fifteen elements (K, Ca, Mg, Al, Ti, V, Mn, Fe, Cu, Zn, Rb, Sr, Zr, Mo, and Sc) were determined in the dried powdered seeds of Usteria guineensis plant by using EDXRF. The results indicate that the plant organ investigated contained K (29458 ± 163 ppm), Ca (3702 ± 54.00 ppm), Mg (5528 ± 1223 ppm), Al (1389 ± 168 ppm) and Fe (167.11 ± 9.20 ppm). The other elements present in smaller quantities were Ti (64 ± 12.00 ppm), Sr (4.74 ± 0.40 ppm), Zn (56.65 ±2.46 ppm), Rb (47.34 ± 1.00 ppm), Zr (20.73 ± 0.67 ppm), and Mo (6.94 ± 0.74 ppm). The elements Sc, Mn, Cu and V were out of limit of detection of the equipment. The above elements detected are essential components of biological structures that mediate vital effect on and play a key role in a variety of the biochemical processes necessary for life.
The Brachial Plexus: More and More Variations
Authors: Elzawawy Ehab Mostafa
Published: February 2022

The brachial plexus is so variable that most of dissected cases will show some form of anatomical variations. In the same person, the right and left sides are not the same. This study was done to identify the variations of the brachial plexus and highlight their clinical significance. The materials of this study included 10 cadavers dissected on both sides to find out the variations of the different parts of the plexus. Variations were found in 85% of cases. Variations included all stages of the plexus. Phrenic nerve took origin from the upper trunk in 10%, while the lateral pectoral nerve took origin by 2 roots from the upper and middle trunks or from the lateral and medial cords in 40%. Abnormal communications were found between the trunks, cords, or branches. Abnormal relations were found between the trunks, cords, or branches and the subclavian or axillary arteries. It is essential to know the exact anatomy of the brachial plexus prior to surgical repair of brachial plexus injuries or prior to supra or infraclavicular plexus block. Variations of brachial plexus are so common. Researchers have been trying for so long to assign specific patternsfor brachial plexus. Their efforts were inutile and now is the time to acknowledge anatomical variations of brachial plexus as the rule.
The 5 Year Outcomes of Early Postoperative Intra-Peritoneal Chemotherapy (EPIC) in High-Grade Appendiceal Cancer – Does regimen length and cancer subtype make a difference?
Authors: Mui Jasmine , Rao Apoorva , Barat Shoma , Kepenekian Vahan , Liauw Winston , Alzahrani Nayef , Morris David
Published: February 2022

Background: Early Post-operative Intra-Peritoneal Chemotherapy (EPIC) following Cytoreductive Surgery (CRS) and Hyperthermic Intra-Peritoneal Chemotherapy (HIPEC) in high-grade appendiceal peritoneal cancer remains controversial with unclear survival benefit. The following study evaluates the survival outcomes in highgrade appendiceal cancer patients receiving varying days of EPIC in addition to CRS and HIPEC, and if survival varied between different appendiceal cancer subtypes. Patients and Methods: A monocentric retrospective analysis of patients with high-grade appendiceal cancers managed from 1994 to 2018 was undertaken. An analysis was performed comparing survival between patients who received HIPEC, HIPEC+EPIC, HIPEC+EPIC <3 days and HIPEC+EPIC ≥3days. All patients received CRS. Results: 212 patients were included in the study. The 5years overall survival was 60% and 55% in the HIPEC+EPIC and HIPEC groups respectively. Patients who received ≥3days of EPIC had an 8% reduction in risk of death compared to those who had <3 days (HR 0.92, CI 0.89-0.94), with a 5-year survival of 62% in the ≥3days group compared to 55% in the <3day group. Patients with signet cell carcinoma had the greatest 5year survival advantage when both HIPEC and EPIC were given (HR 01.23, CI 01.21-01.26). Conclusion: EPIC in combination with HIPEC and CRS offers survival benefit at 5years in high-grade appendiceal peritoneal cancer and is most advantageous in signet cell carcinoma. Completing a ≥3day course of EPIC increases chance of survival at 5years compared to a <3 days course.
SARS-CoV-2 Spike Glycoprotein Binds Heparan Sulfate Chains and N-Glycans in Psoriatic Keratinocytes: A Hypothesis.
Authors: Enrique Arciniegas , Luz Marina Carrillo , Antonio Salgado , Jaime Piquero , Diana Ortiz
Published: February 2022

Psoriasis vulgaris, the most common form of psoriasis, is a chronic inflammatory skin disease that affects 2-3% of the worldwide population. It has been reported in patients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) suggesting the percutaneous transmission of this infection which may cause the exacerbation of psoriasis. Interestingly, elevated expression of ACE2 receptor on differentiating keratinocytes and basal cell layer of the epidermis of patients with psoriasis and COVID-19 involving pro inflammatory cytokines such as IFN-γ and IL-17, has been reported; however little is known about the participation of other receptors expressed on the surface of psoriatic keratinocytes, in the SARS-CoV-2 infection. Here we hypothesize that, in the skin of patients with psoriasis who have been diagnosed with COVID-19, the interaction of the SARS-CoV-2 S glycoprotein with the HSPGs Synd-1 and CD44 through their HS side chains and N-linked glycan, and Gal-3 and Gal-8 through the N- glycans located on the ACE2, integrin-β1, CD147, IFN-γR and IL-17A-R, would generate a Gal-glycan lattice at the surface of SARS-CoV-2 virus and psoriatic keratinocyte. Such Gal-glycan lattice in addition to influence keratinocyte proliferation and terminal differentiation, might induce conformational changes in the SARS-CoV-2 S glycoprotein facilitating the attachment and virus entry. We consider that future work will be required to understand the mechanisms regulating Gal-glycan lattice assembly during psoriatic keratinocyte and SARS-CoV-2 interaction as well as for the development of new inhibitors of virus attachment and internalization.
Serum Micronutrient Levels In Premature Canities: A Systematic Review and Meta-analysis.
Authors: Camelia Nur , Malik Diah Adriani , Riyanto Puguh , Budiastuti Asih , Widayati Retno Indar , M Muslimin , H Hardian
Published: February 2022

Background: Premature canities, also known as premature graying of hair, is the graying of hair before 20 years old in Caucasians, before 25 years old in Asians, and before 30 years old in African–Americans. The risk factors for premature canities are multifactorial. The role of micronutrient deficiency has long been suggested to be involved in the etiopathogenesis of premature canities. The management of premature canities remains limited and far from satisfactory; hence, knowing what vitamins and minerals can help in treating premature canities is vital. Aim: This study aims to analyze serum vitamin B12, iron, ferritin, copper, calcium, and zinc levels in premature canities. Methods: The MEDLINE/PubMed electronic database, Cochrane library, ClinicalTrials.gov, EBSCO, Scopus, ProQuest, Cambridge Core, reference lists, conference proceedings, and researchers in fields of eligible studies were searched. Twelve studies (n = 1791 subjects) were included in qualitative analysis of which nine studies (n = 1381 subjects) were included in meta-analysis. Serum levels of micronutrients (vitamin B12, iron, ferritin, copper, calcium, and zinc) were compared in the premature canities and nonpremature canities groups. Result: Pooling of data using fixed-effects model found the overall effect mean difference serum vitamin B12 level was −0.697 ± 0.105 (95% CI = −0.904 to −0.490), p < 0.001. The overall mean difference serum iron level was 0.146 ± 0.105 (95% CI = −0.058 to 0.350), p = 0.161. The overall mean difference serum ferritin level was 0.720 ± 0.071 (95% CI = 0.585 to 0.854), p < 0.001. The overall mean difference serum copper level was 0.230 ± 0.118 (95% CI = −0.003 to 0.463, p = 0.053. The overall mean difference serum calcium level was −0.443 ± 0.114 (95% CI = −0.655 to −0.212), p < 0.001. The overall mean difference serum zinc level was −0.104 ± 0.138 (95% CI = 0.377 to 0.170, p = 0.457. Qualitative analysis showed that vitamin B12 plays an important role in DNA synthesis in the proliferation of hair follicle cells and in melanogenesis. Iron, ferritin, copper, calcium, and zinc also play important roles in stabilizing and increasing tyrosinase activity in several stages of the melanogenesis process. Conclusion: The meta-analysis showed that serum levels of vitamin B12, ferritin, and calcium were significantly lower in premature canities. Although the lower serum iron, copper, and zinc levels were not significantly different in premature canities compared with nonpremature canities. Qualitative analysis found that deficiency of vitamin B12, iron, ferritin, zinc, copper, and calcium can affect the physiology of hair melanogenesis that causing premature canities.
DEIKSIS PERSONA DALAM GELAR WICARA MATA NAJWA: KAJIAN PRAGMATIK
Authors: Hidajati Enny , Zanatia Debby Ayu
Published: February 2022

This study aims to describe the use form of persona deixis contained in the Mata Najwa's talk show in the January 202I episode. Research data in the form of speech from news presenter, Najwa Shihab in the affirmation section. This study uses a descriptive method with data analysis techniques. The results of this study show that the use of the form of persona deixis is often used by Najwa Shihab, as the presenter in the Mata Najwa’s talk show includes: (1) first person deixis, “I” used to respect the interlocutor and the habit of using formal variety; (2) second person deixis, “we” used to represent himself and her interlocutor, “Mr./Mrs.” used to respect the interlocutor who has a much older age and higher social status; and (3) third person deixis, “his/hers” used to refer to the possession of the third person being discussed.
Gastrin-17 Levels in Pre-malignancy Gastritis Lesions
Authors: Halim Sahat , Alamnsyah Siregar Gontar
Published: February 2022

Background: Gastritis is an inflammatory process on the lining of the stomach that could be caused by various factors. Untreated inflammatory processes could lead to ulcers. Gastrin hormone is released by gastrin-secreting enteroendocrine cells (G cells) in the stomach, which influence the secretion of gastric acid and helps the proliferation of gastric epithelial cells. Its abnormal secretion in H. pylori infection, with food-stimulated excessive release of gastrin, is the most prominent abnormality. One concern is the relationship of excess gastrin secretion to the incidence of gastric cancer. This study aimed to show the difference in gastrin levels on patients with gastritis, both with and without pre-malignant lesions.

Methods: This research was a cross-sectional study with 40 samples that had met the inclusion and exclusion criteria. Endoscopy was performed to assess the gastric mucosa and tissue biopsy was performed afterward. The data was analysed in univariate and bivariate ways.

Results: From this study, 20 people were positive for pre-malignant lesions (50%). Mann–Whitney test analysis was used to analyse the data and showed there was a significant difference between gastrin levels on patients with gastritis with and without pre-malignant lesions, with a p value of 0.01.

Conclusion: There is a significant difference between gastrin levels in patients with gastritis with and without pre-malignant lesions, which could be the basis for early detection of patients with gastric cancer.
Information Technology Adoption by Internal Auditors in Public Sector: Antesedents and Consequences
Authors: Koesanto Stefani Made Ayu Artharini , Husnatarina Fitria , Rahmaddian Rahmaddian , Madya Faizal
Published: February 2022

The understanding of Information Technology (IT) adopted by internal government auditors is related to developments in the IT sector in the public sector, such as e-government applications. The purpose of this study is to provide an argument for the motivation for IT adoption when the internal auditors and to identify the factors that influence IT adoption and the influence of IT adoption on the performance of internal auditors in the public sector. This research used quantitative methods and data analysis using Structural Equation Modeling (SEM) with 79 auditors from the Inspectorate within the scope of Central Kalimantan Province. Findings. The results showed that only the perceived benefits variable had a positive and significant effect on IT adoption, while the compatibility variables, top management support, organizational readiness, the external force had a positive but insignificant effect on IT adoption as an antecedent part, while IT adoption had an effect, positive and significant impact on government performance as a consequence of IT adoption. This study provides a practical understanding for government auditors that in carrying out their duties, especially in the new normal order conditions, that the adoption of IT is important to do to produce a good performance.
Reflections on Teacher Job Satisfaction: The Role of Principal Supervision, Organizational Culture, Motivation, and Compensation
Authors: Lie Darwin , Sherly Sherly , Dharma Edy , Wakhyuni Emi , Sudirman Acai
Published: February 2022

The success and failure of an organization is influenced by competent Human Resources (HRM) who are oriented towards efficiency, quality, and productivity. This research aims to determine the role of principal supervision, organizational culture, motivation, and compensation as predictors of job satisfaction. The research design used a quantitative approach to causality. To obtain research data using documentation instruments and distributing questionnaires online. The sample used in the study was 215 respondents. The basis for determining the sample is oriented towards a non-probability sampling approach using a purposive sampling formula. To examine the relationship between principal supervision, organizational culture, motivation, and compensation on job satisfaction, then the structural equation modeling (SEM) approach is used using partial least squares. Findings. In accordance with the results of the study, it was found that the supervision of the principal has a significant effect on job satisfaction. Furthermore, organizational culture has a significant influence on job satisfaction. Furthermore, motivation has a significant effect on job satisfaction. Then compensation also has a significant effect on job satisfaction. motivation has a significant effect on job satisfaction. Then compensation also has a significant effect on job satisfaction. motivation has a significant effect on job satisfaction. Then compensation also has a significant effect on job satisfaction.
Village Fund Financial Fraud Prevention Model Using Analytical Hierarchy Process Method
Authors: Taqi Muhamad , Ismail Tubagus , Meutia Meutia , Sabaruddinsah Sabaruddinsah , Arifin Bustanul
Published: February 2022

The objectives of this study are (1). Identify the factors that cause fraud in village fund management in Banten Province (2). Develop a village fund fraud prevention model using the Analytical Hierarchy Process method. Data collection methods were carried out by in-depth interviews and Focus Group Discussion (FGD) by inviting academics and experts. The analysis technique uses the Analytical Hierarchy Process (AHP) to model the prevention of village fund fraud in Banten Province. Findings. The results of this study indicate that the actor who is considered the most dominant in the occurrence of fraud is the Village Head, and the strategy that is considered the most dominant in preventing fraud is to narrow the opportunities. When viewed from the perspective of a strategy to minimize pressure, the most important aspect is the change in external auditors, from a strategy perspective of narrowing opportunities, the most important aspect is to streamline monitoring, then from the perspective of negative rationalization strategies and positive competency strategies, the most important aspects include ethics education moral and management change, and the last aspect of the closeness of the ruler is the most important aspect in the strategy perspective to reduce arrogance.
How to Improve Scientific Publication Performance of Private University Lecturers: an Empirical Analysis on Individual and Institutional Factors
Authors: Harsasi Mairani , Hutagaol Manuntun Parulian , Baga Lukman M , Sailah Illah
Published: February 2022

Indonesian scientific publications on Scopus show encouraging increase by being listed as number 1 in Southeast Asia. However, fewer literary contribution by private university compared to those made by state university. Thus this study investigates which factors will impact publication performance of private university lecturers. Using multiple linear regression analysis of 226 data, it is found that motivation, self-efficacy, research skills, research time, and training are proven to have positive impact on publication performance. Findings. Teaching workload was found to have significant negative impact, while supporting resources were the only variable that had no impact on publication performance. This research has contribution towards institutional policies in encouraging lecturers to produce scientific publications by strengthening the influencing factors.
Gastrointestinal Autonomic Neuropathy Exacerbates Gut Microbiota Dysbiosis in Adult Patients With Type 2 Diabetes Mellitus
Authors: Du Yuhui , Neng Qiongli , Li Yu , Kang Yongbo , Guo Liqiong , Huang Xinwei , Chen Minghui , Yang Fan , Hong Jingan , Zhou Shuai , Zhao Jianhua , Yu Fubing , Su Heng , Kong Xiangyang
Published: February 2022

Objective

The diabetic autonomic neuropathy is one of the most common complications in type 2 diabetes mellitus (T2DM), especially gastrointestinal autonomic neuropathy (GAN), which occurs in up to 75% of patients. The study aimed to investigate the gut microbiota composition, structure, and function in T2DM patients with GAN (T2DM_GAN) and set up a link between gut microbiota and clinical characteristics of patients.

Methods

DNA was extracted from fecal samples of three groups using the kit method: healthy volunteers (n = 19), the patients with T2DM (n = 76), and T2DM_GAN (n = 27). Sequencing of 16S ribosomal DNA was performed using the MiSeq platform.

Results

According to the clinical data, higher age, lower triglyceride, and lower body mass index were the main features of patients with T2DM_GAN. The gut microbiota analysis showed that Bacteroidetes, Firmicutes, and Proteobacteria constituted the three dominant phyla in healthy individuals. In addition, the gut microbiota structure and function of T2DM_GAN patients were clearly different from that of T2DM patients. T2DM patients were characterized by Fusobacteria, Fusobacteriia, Fusobacteriales, Fusobacteriaceae, Fusobacterium, Lachnoclostridium, and Fusobacterium_mortiferum. Those gut microbiota may be involved in carotenoid and flavonoid biosyntheses. Relatively, the Gammaproteobacteria, Enterobacteriales, Enterobacteriaceae, Escherichia-Shigella, Megasphaera, Escherichia_coli, and Megasphaera_elsdenii were characteristic in the T2DM_GAN patients. Those may be involved in bacterial invasion of epithelial cells and pathogenic Escherichia coli infection.

Conclusions

GAN exacerbated gut microbiota dysbiosis in adult patients with T2DM. The findings indicated that phyla Fusobacteria and class Gammaproteobacteria were closely related to the occurrence of T2DM. Especially the latter may promote T2DM_GAN.
Ischemic Stroke in Non-Gender-Related CHA2DS2-VA Score 0~1 Is Associated With H2FPEF Score Among the Patients With Atrial Fibrillation
Authors: Kim Min , Yu Hee Tae , Kim Tae-Hoon , Lee Dae-In , Uhm Jae-Sun , Kim Young Dae , Nam Hyo Suk , Joung Boyoung , Lee Moon-Hyoung , Heo Ji Hoe , Pak Hui-Nam
Published: February 2022

Background

Ischemic strokes (ISs) can appear even in non-gender-related CHA2DS2-VA scores 0~1 patients with atrial fibrillation (AF). We explored the determinants associated with IS development among the patients with non-gender-related CHA2DS2-VA score 0~1 AF.

Methods and Results

In this single-center retrospective registry data for AF catheter ablation (AFCA), we included 1,353 patients with AF (24.7% female, median age 56 years, and paroxysmal AF 72.6%) who had non-gender-related CHA2DS2-VA score 0~1, normal left ventricular (LV) systolic function, and available H2FPEF score. Among those patients, 113 experienced IS despite a non-gender-related CHA2DS2-VA score of 0~1. All included patients underwent AFCA, and we evaluated the associated factors with IS in non-gender-related CHA2DS2-VA score 0~1 AF. Patients with ISs in this study had a lower estimated glomerular filtration rate (eGFR) (p < 0.001) and LV ejection fraction (LVEF; p = 0.017), larger LA diameter (p < 0.001), reduced LA appendage peak velocity (p < 0.001), and a higher baseline H2FPEF score (p = 0.018) relative to those without ISs. Age [odds ratio (OR) 1.11 (1.07–1.17), p < 0.001, Model 1] and H2FPEF score as continuous [OR 1.31 (1.03–1.67), p = 0.028, Model 2] variable were independently associated with ISs by multivariate analysis. Moreover, the eGFR was independently associated with IS at low CHA2DS2-VA scores in both Models 1 and 2. AF recurrence was significantly higher in patients with IS (log-rank p < 0.001) but not in those with high H2FPEF scores (log-rank p = 0.079), respectively.

Conclusions

Among the patients with normal LVEF and non-gender-related CHA2DS2-VA score 0~1 AF, the high H2FPEF score, and increasing age were independently associated with IS development (ClinicalTrials.gov Identifier: NCT02138695).
Relation Between Plasma Proteomics Analysis and Major Adverse Cardiovascular Events in Patients With Stable Coronary Artery Disease
Authors: Dregoesc Mihaela Ioana , Ţigu Adrian Bogdan , Bekkering Siroon , van der Heijden Charlotte D. C. C. , Bolboacǎ Sorana Daniela , Joosten Leo A. B. , Visseren Frank L. J. , Netea Mihai G. , Riksen Niels P. , Iancu Adrian Corneliu
Published: February 2022

Objective

Despite the advances in the control of traditional risk factors, coronary artery disease (CAD) remains the greatest cause of morbidity and mortality. Our aim was to establish the relation between plasma proteomics analysis and the risk of cardiovascular events in patients with stable CAD.

Materials and Methods

Patients with stable CAD and documented coronary atherosclerosis were screened for inclusion. Using proximity extension assays, 177 plasma proteins were simultaneously measured. The endpoint consisted of the first major adverse cardiovascular event (MACE) and was the composite of cardiovascular death, acute coronary syndrome, stroke, transient ischemic attack, or acute limb ischemia at 18 months follow-up. Cox proportional-hazards regression with adjustment for multiple comparisons was used to identify biomarkers for the outcomes of interest.

Results

The cohort consisted of 229 patients. Six mediators were associated with MACE (p < 0.001). For these markers, the risk of MACE was calculated: tumor necrosis factor receptor superfamily member 13B (HR = 1.65; 95% CI: 1.30–2.10), C-C motif chemokine-3 (HR = 1.57; 95% CI: 1.23–1.98), decorin (HR = 1.65; 95% CI: 1.26–2.16), fibroblast growth factor-23 (HR = 1.56; 95% CI: 1.23–1.99), tumor necrosis factor-related apoptosis-inducing ligand-receptor 2 (TRAIL-R2) (HR = 1.61; 95% CI: 1.23–2.11), and tumor necrosis factor receptor superfamily member 10A (HR = 1.69; 95% CI: 1.25–2.29). Except for TRAIL-R2, the other proteins were associated with MACE independent of age, sex, diabetes mellitus, or estimated glomerular filtration rate.

Conclusions

In patients with stable CAD, five novel biomarkers were identified as independent risk factors for adverse outcomes. Novel biomarkers could represent pharmacological targets for the prevention of adverse cardiovascular events.
Regenerative Endodontic Procedures in Immature Permanent Teeth With Dental Trauma: Current Approaches and Challenges
Authors: Zhou Caixia , Yuan Zhenglin , Xu Hanxin , Wu Linrui , Xie Chun , Liu Jiarong
Published: February 2022

After dental trauma to immature permanent teeth (IPT), there can be pulpitis, necrotic, and periapical periodontitis, which will halt further root development. Traditional endodontic root canal treatments and apexification cannot revitalize the necrotic pulp to revitalize the tooth to promote further root development. As a consequence, IPT with thin dentinal walls can be prone to fracture and if a fracture occurs, the patient will likely suffer the loss of the tooth. In an attempt to save IPT, there has been a growing interest among dentists to use regenerative endodontic procedures (REPs) to revitalize a replace dental pulp to continue root development and strengthen the dentinal walls to help prevent a subsequent loss of the tooth. However, the effectiveness of REPs and the precise methods to successfully accomplish REPs are controversial. Therefore, the objective of this review is to compare the different approaches to REPs in case reports by highlighting their advantages and limitations.
Cognitive Behavioral Training Reduces Socially Anxious Classroom Behavior in Primary School Students
Authors: Casale Gino , Haarhoff Daniel
Published: February 2022

Many students show symptoms of social anxiety. Cognitive behavioral training (CBT) has been shown to be effective in reducing symptom behavior in therapeutic and school contexts, but there are hardly any single-case studies that examine the individual effectiveness in school settings. Furthermore, the extent to which differential responsivity effects are exhibited by students has not been examined yet. This single-case study with AB design investigates the effects of a CBT on the socially anxious classroom behavior of students with severe symptoms of social anxiety. Two female and two male students (9–10 years old) of an inclusive primary school in Germany participated in the CBT over a period of twelve weeks. Socially anxious behaviors were measured daily with Direct Behavior Rating-Multi Item Scales. Visual analyses, overlap indices, and regression models show a substantial behavioral improvement for all students during the intervention. However, there are differences between the students in terms of which specific behaviors were improved and whether the behavioral improvements took place immediately after the implementation of the intervention or continuously from measurement to measurement in the B phase. The results highlight the relevance of specific and individualized behavioral goals for CBT in school, although the effects should be replicated in experimental studies.
Dynamic Gene Expression and Alternative Splicing Events Demonstrate Co-Regulation of Testicular Differentiation and Maturation by the Brain and Gonad in Common Carp
Authors: Zhao Yuanli , Chen Kuangxin , Liu Fei , Jiang Mouyan , Chen Zonggui , Chen Huijie , Song Yanlong , Tao Binbin , Cui Xuefan , Li Yongming , Zhu Zuoyan , Chen Ji , Hu Wei , Luo Daji
Published: February 2022

The common carp (Cyprinus carpio) accounts for approximately 10% of the annual freshwater aquaculture production and is an ideal model to study cyprinidae reproduction. Female common carp grow faster than the males; therefore, related research presents an opportunity with high application value. Although we have a detailed understanding of common carp’s early gonadal differentiation process, information about genome-wide gene expression, regulation, and underlying molecular mechanisms during this process remain limited. Here, time-course data comprising six key stages during testicular differentiation and maturation were investigated to further understand the molecular mechanisms underlying the testicular development in cyprinid species. After integrating these time-series data sets, common carp genome, including 98,345 novel transcripts and 3,071 novel genes were re-annotated and precisely updated. Gene co-expression network analysis revealed that the ubiquitin-mediated proteolysis pathway was essential for metabolism during testicular differentiation in the endocrine system of C. carpio. Functional enrichment analyses indicated that genes mainly related to amino acid metabolism and steroid hormone synthesis were relatively highly expressed at the testicular undifferentiation stages, whereas genes associated with cell cycle and meiosis were expressed from the beginning of testicular differentiation until maturation. The dynamics of alternative splicing events demonstrated that exon skipping accounted for majority of the alternative splicing events in the testis and the brain during gonad development. Notably, several potential male-specific genes (fanci and sox30) and brain-specific genes (oxt, gad2, and tac1, etc.) were identified. Importantly, we traversed beyond the level of transcription to test for stage- and gonad-specific alternative splicing patterns between the brain and testis. This study is the first to describe a comprehensive landscape of alternative splicing events and gene expression patterns during gonadogenesis in common carp. This work is extremely valuable to elucidate the mechanisms underlying gonadal differentiation in Cyprinidae as well as other fish species.
Temporal Soundscape Patterns in a Panamanian Tree Diversity Experiment: Polycultures Show an Increase in High Frequency Cover
Authors: Müller Sandra , Mitesser Oliver , Oschwald Linda , Scherer-Lorenzen Michael , Potvin Catherine
Published: February 2022

In this ecoacoustic study we used the setting of a tropical tree diversity planted forest to analyze temporal patterns in the composition of soundscapes and to test the effects of tree species richness on associated biodiversity measured as acoustic diversity. The analysis of soundscapes offers easy, rapid and sustainable methods when assessing biodiversity. During the last years the quantification of regional or global acoustic variability in sounds and the analysis of different soundscapes has been evolving into an important tool for biodiversity conservation, especially since case studies confirmed a relationship between land-use management, forest structure and acoustic diversity. Here we analyzed soundscapes from two seasons (dry and rainy season) and aurally inspected a subset of audio recordings to describe temporal patterns in soundscape composition. Several acoustic indices were calculated and we performed a correlation analysis and a non-metric multidimensional scaling analysis to identify acoustic indices that: (i) were complementary to each other and such represented different aspects of the local soundscapes and (ii) related most strongly to differences in acoustic composition among tree species richness, season and day phase. Thus, we chose “High Frequency Cover,” “Bioacoustic Index,” and “Events Per Second” to test the hypothesis that acoustic diversity increases with increasing tree species richness. Monocultures differed significantly from polycultures during night recordings, with respect to High Frequency Cover. This index covers sounds above 8 kHz and thus represents part of the orthopteran community. We conclude that increasing tree species richness in a young tropical forest plantation had positive effects on the vocalizing communities. The strongest effects were found for acoustic activity of the orthopteran community. In contrast to birds, orthopterans have smaller home ranges, and are therefore important indicator species for small scale environmental conditions.
Physical Activity and Systemic Lupus Erythematosus Among European Populations: A Two-Sample Mendelian Randomization Study
Authors: Huang Shuo , Tian Fengyuan , Yang Xiaoxuan , Fang Sijia , Fan Yongsheng , Bao Jie
Published: February 2022

Background: The causal relationship between physical activity (PA) and systemic lupus erythematosus (SLE) remains uncertain. We aimed to assess the causal effect of PA on SLE by two-sample Mendelian randomization (MR) study.

Methods: Summary statistics of SLE were obtained from a genome-wide association study (GWAS) meta-analysis of European descent, including 4,036 cases and 6,959 controls. Genetic instruments for PA, including MVPA, VPA, SSOE, and average acceleration, were identified from a large-scale GWAS meta-analysis among 377,234 individuals of European ancestry from United Kingdom biobank and Atherosclerosis Risk in Communities (ARIC) study, and another GWAS with 91,105 European participants was employed for sedentary behavior. The two-sample MR study was conducted to estimate causal relationship between PA and SLE, with the inverse-variance weighted (IVW) method, simple- and weighted-median method. Moreover, MR-Egger regression, MR-PRESSO and leave-one-out analysis were performed to evaluate the potential pleiotropy effect.

Results: In the end, we totally selected 37 SNPs (15 SNPs for MVPA, 5 SNPs for VPA, 9 SNPs for SSOE, 5 SNPs for average acceleration and 3 SNPs for sedentary behavior). According to the IVW results, as the primary method, we found that genetically predicted PA was not causally associated with risk of SLE (MVPA: OR 0.44, 95% CI 0.09–2.10, p = 0.305; VPA: OR 0.20, 95% CI 0.00–18.97, p = 0.490; SSOE: OR 0.96, 95% CI 0.03–29.24, p = 0.983; average acceleration: OR 0.91, 95% CI 0.79–1.05, p = 0.190; sedentary behavior: OR 1.54, 95% CI 0.35–6.81, p = 0.572). MR-Egger, MR-PRESSO, and leave-one-out analysis did not indicate horizontal pleiotropy.

Conclusions: Our MR study suggested that genetically predicted PA was not causally associated with SLE among the European populations.
Immune ULBP1 is Elevated in Colon Adenocarcinoma and Predicts Prognosis
Authors: Ruan Guo-Tian , Xie Hai-Lun , Zhu Li-Chen , Ge Yi-Zhong , Yan Lin , Liao Cun , Gong Yi-Zhen , Shi Han-Ping
Published: February 2022

Background: Colon adenocarcinoma (COAD) is still the main cause of cancer deaths worldwide. Although immunotherapy has made progress in recent years, there is still a need to improve diagnosis, prognosis, and treatment tools. UL-16 binding protein 1 (ULBP1) is a ligand that activates the receptor natural killer cell group 2 receptor D (NKG2D) and plays an important immunomodulatory role. We aimed to investigate the clinical significance of ULBP1 in COAD.

Methods: We obtained the relevant data from The Cancer Genome Atlas (TCGA). A total of 438 patients with COAD were included in this study, with a mean age of 67.1 ± 13.03 years old, of which 234 (53.42%) were male. The diagnostic value of COAD tumor tissues and adjacent tissues was analyzed by ROC curve. Univariate and multivariate survival analysis investigated the prognostic value of ULBP1 gene, and Gene Set Enrichment Analysis (GSEA) curve was performed to analyze the biological process and enriched enrichment pathway of ULBP1 in COAD. Combination survival analysis investigated the combined prognostic effect of prognostic genes.

Results:ULBP1 gene had a high diagnostic value in COAD [AUC (TCGA) = 0.959; AUC (Guangxi) = 0.898]. Up-regulated ULBP1 gene of patients with COAD predicted a worse prognosis compared to those patients with down-regulated ULBP1 gene (Adjusted HR = 1.544, 95% CI = 1.020–2.337, p = 0.040). The GSEA showed that ULBP1 was involved in the apoptotic pathway and biological process of T cell mediated cytotoxicity, regulation of natural killer cell activation, and T cell mediated immunity of COAD. The combination survival analysis showed that the combination of high expression of ULBP1, AARS1, and DDIT3 would increase the 2.2-fold death risk of COAD when compared with those of low expression genes.

Conclusion: The immune-related ULBP1 gene had diagnostic and prognostic value in COAD. The combination of ULBP1, AARS1, and DDIT3 genes could improve the prognostic prediction performance in COAD.
Comprehensive Transcriptome Analysis of mRNA Expression Patterns Associated With Enhanced Biological Functions in Periodontal Ligament Stem Cells Subjected to Short-Term Hypoxia Pretreatment
Authors: Li Zhi-Bang , Yang Hui-Qi , Li Kun , Yin Yuan , Feng Su-Su , Ge Shao-Hua , Yu Yang
Published: February 2022

Short-term hypoxia pretreatment significantly enhances periodontal ligament stem cell (PDLSC)-based periodontal tissue regeneration by improving various cellular biological functions, but the underlying mechanisms remain unclear. In this study, based on RNA sequencing (RNA-seq), we comprehensively analyzed the possible regulatory mechanisms of the short-term hypoxic effects on the biological functions of healthy and inflammatory PDLSCs. A total of 134 and 164 differentially expressed genes (DEGs) were identified under healthy and inflammatory conditions, respectively. Functional enrichment analyses indicated that DEGs under both conditions share certain biological processes and pathways, including metabolic processes, developmental processes, reproductive processes, localization, immune system processes and the HIF-1 signaling pathway. The DEGs identified under inflammatory conditions were more significantly enriched in cell cycle-related processes and immune-related pathways, while DEGs identified under healthy condition were more significantly enriched in the TGF-β signaling pathway. A protein-protein interaction network analysis of the 59 DEGs in both conditions was performed, and 15 hub genes were identified. These hub genes were mainly involved in glycolysis, the cellular response to hypoxia, cell differentiation, and immune system processes. In addition, we found that hypoxia induced significant differential expression of genes associated with proliferation, differentiation, migration, apoptosis and immunoregulation under both healthy and inflammatory conditions. This study provides comprehensive insights into the effects of short-term hypoxia on the biological functions of PDLSCs and suggests a potentially feasible strategy for improving the clinical effectiveness of cell-based periodontal tissue engineering.
Chloroquine Suppresses Effector B-Cell Functions and Has Differential Impact on Regulatory B-Cell Subsets
Authors: Ma Xin , Dai Yang , Witzke Oliver , Xu Shilei , Lindemann Monika , Kribben Andreas , Dolff Sebastian , Wilde Benjamin
Published: February 2022

Objectives

Chloroquine (CQ) is approved for treatment of B-cell mediated diseases such as rheumatoid arthritis and systemic lupus erythematosus. However, the exact mode of action in these diseases has not been studied and it remains unclear which effect CQ has on B-cells. Thus, it was the aim of this study to investigate to which extent CQ affects functionality of effector and regulatory B-cell.

Methods

For this purpose, B-cells were isolated from peripheral blood of healthy controls and renal transplant patients. B-cells were stimulated in presence or absence of CQ and Interleukin-10 (IL-10) and Granzyme B (GrB) secretion were assessed. In addition, effector functions such as plasma cell formation, and Immunoglobulin G (IgG) secretion were studied.

Results

CQ suppressed Toll-Like-Receptor (TLR)-9 induced B-cell proliferation in a dose-dependent manner. IL-10pos regulatory B-cells were suppressed by CQ already at low concentrations whereas anti-IgG/IgM-induced GrB secreting regulatory B-cells were less susceptible. Plasma blast formation and IgG secretion was potently suppressed by CQ. Moreover, purified B-cells from renal transplant patients were also susceptible to CQ-induced suppression of effector B-cell functions as observed by diminished IgG secretion.

Conclusion

In conclusion, CQ had a suppressive effect on IL-10 regulatory B-cells whereas GrB secreting regulatory B-cells were less affected. Effector functions of B-cells such as plasma blast formation and IgG secretion were also inhibited by CQ. Effector B-cells derived from renal transplant patients already under immunosuppression could be suppressed by CQ. These findings may partly explain the clinical efficacy of CQ in B-cell mediated autoimmune diseases. The application of CQ in other disease contexts where suppression of effector B-cells could offer a benefit, such as renal transplantation, may hypothetically be advantageous.
Astrocytes and Inflammatory T Helper Cells: A Dangerous Liaison in Multiple Sclerosis
Authors: Kunkl Martina , Amormino Carola , Tedeschi Valentina , Fiorillo Maria Teresa , Tuosto Loretta
Published: February 2022

Multiple Sclerosis (MS) is a neurodegenerative autoimmune disorder of the central nervous system (CNS) characterized by the recruitment of self-reactive T lymphocytes, mainly inflammatory T helper (Th) cell subsets. Once recruited within the CNS, inflammatory Th cells produce several inflammatory cytokines and chemokines that activate resident glial cells, thus contributing to the breakdown of blood-brain barrier (BBB), demyelination and axonal loss. Astrocytes are recognized as key players of MS immunopathology, which respond to Th cell-defining cytokines by acquiring a reactive phenotype that amplify neuroinflammation into the CNS and contribute to MS progression. In this review, we summarize current knowledge of the astrocytic changes and behaviour in both MS and experimental autoimmune encephalomyelitis (EAE), and the contribution of pathogenic Th1, Th17 and Th1-like Th17 cell subsets, and CD8+T cells to the morphological and functional modifications occurring in astrocytes and their pathological outcomes.
The Predictive Potential of the Baseline C-Reactive Protein Levels for the Efficiency of Immune Checkpoint Inhibitors in Cancer Patients: A Systematic Review and Meta-Analysis
Authors: Han Cheng-Long , Meng Guang-Xiao , Ding Zi-Niu , Dong Zhao-Ru , Chen Zhi-Qiang , Hong Jian-Guo , Yan Lun-Jie , Liu Hui , Tian Bao-Wen , Yang Long-Shan , Xue Jun-Shuai , Li Tao
Published: February 2022

Background

The relationship between baseline C-reactive protein (CRP) level and the prognosis of cancer patients receiving immune checkpoint inhibitor (ICI) treatment remains controversial. The aim of this meta-analysis was to clarify whether baseline CRP level can serve as a biomarker to predict the efficiency of ICI therapy.

Methods

All associated articles published in the Cochrane Library, EMBASE, and PubMed databases from the inception of the database to December 30, 2021, were retrieved. Progression-free survival (PFS) and overall survival (OS) outcomes were meta-analyzed using the random-effects model and adjusted using the trim-and-fill method because of publication bias.

Results

Thirty-three studies (6,124 patients) conducted between 2013 and 2021 were identified. The pooled outcomes implied that high baseline CRP level patients had significantly worse OS (adjusted pooled value for univariate and multivariate analysis outcomes: HR = 1.48, 95% CI = 1.41–1.56; HR = 1.46, 95% CI = 1.34–1.59) and PFS (adjusted pooled value for univariate and multivariate analysis outcomes: HR = 1.29, 95% CI = 1.15–1.45; HR = 1.20, 95% CI = 1.02–1.40) than low baseline CRP level patients, irrespective of cancer or ICI type. Further analysis indicated that 1 mg/dl was appropriate as a cutoff value for determining the low or high level of baseline CRP to predict the OS or PFS of cancer patients receiving ICI treatment (univariate analysis: HR = 1.56, 95% CI = 1.24–1.97, P = 0.909; multivariate analysis: HR = 1.58, 95% CI = 1.23–2.03, P = 0.521).

Conclusions

High baseline CRP level (>1 mg/dl) may be an indicator for worse OS and PFS of cancer patients treated with ICIs. More high-quality prospective studies are warranted to assess the predictive value of CRP for ICI treatment.
The Role of Eddies in the North Atlantic Decadal Variability
Authors: Yang Chunxue , Bricaud Clément , Drévillon Marie , Storto Andrea , Bellucci Alessio , Santoleri Rosalia
Published: February 2022

The role of eddies in the North Atlantic decadal variability is investigated in this study by using two ocean reanalyses, including an eddy permitting (or eddy poor) reanalysis with horizontal resolution of 0.25 degree and 75 vertical levels and an eddy resolving (or eddy rich) reanalysis with horizontal resolution of 1/12 degree and 50 vertical levels. The prominent mid-1990s warming and post-2005 cooling trend as part of the North Atlantic decadal variability is well displayed in both reanalyses with no significant difference between them. The main driver of the mid-1990s warming and post-2005 cooling trend is the increase and reduction of the meridional ocean heat transport showing similar patterns in both reanalyses. The relative contribution of the heat transport anomalies from eddies to the total heat transport anomalies is slightly larger in eddy resolving than in eddy permitting ocean reanalysis. However, the total mean ocean meridional heat transport increases by 10% in eddy resolving reanalysis with respect to eddy permitting reanalysis and is mainly due to the associated increase of the mean states (temperature and velocity). Therefore, the increase of eddy population due to the increase of horizontal resolution, found by comparing the two datasets, does not affect the MHT anomalies significantly and, consequently, the North Atlantic decadal variability. It is found that the importance of the model horizontal resolution for the North Atlantic decadal variability depends on the interaction between the eddies (small scale) and the mean state (large scale) at decadal time scales. Although the fast increase of computational power will allow soon for eddy-resolving predictions, the need to use high resolution modeling tools for decadal predictions depends on the importance of initialization methods and the interaction between small scale and large-scale variabilities. This study has pivotal implications for the development of North Atlantic decadal prediction systems.
Benchmarking Autonomous Scattering Experiments Illustrated on TAS
Authors: Teixeira Parente Mario , Schneidewind Astrid , Brandl Georg , Franz Christian , Noack Marcus , Boehm Martin , Ganeva Marina
Published: February 2022

With the advancement of artificial intelligence and machine learning methods, autonomous approaches are recognized to have great potential for performing more efficient scattering experiments. In our view, it is crucial for such approaches to provide thorough evidence about respective performance improvements in order to increase acceptance within a scientific community. Therefore, we propose a benchmarking procedure designed as a cost-benefit analysis that is applicable to any scattering method sequentially collecting data during an experiment. For a given approach, the performance assessment is based on how much benefit, given a certain cost budget, it is able to acquire in predefined test cases. Different approaches thus get a chance for comparison and can make their advantages explicit and visible. Key components of the procedure, i.e., cost measures, benefit measures, and test cases, are made precise for the setting of three-axes spectrometry (TAS) as an illustration. Finally, we discuss neglected aspects and possible extensions for the TAS setting and comment on the procedure’s applicability to other scattering methods. A Python implementation of the procedure to simplify its utilization by interested researchers from the field is also provided.