bluuebunny/crossref_metadata_2025 huggingface dataset:
Storia di una ricerca
Authors: Paola Domingo , Franchi Riccardo , Ravera Lorenzo
Published: November 2022

L’attività didattica descritta ha avuto origine da un classico problema di calcolo combinatorio e probabilità che si sono posti due studenti di una quinta liceo scientifico, che sono anche due degli autori di questo articolo. Si descrivono i primi tentativi di risoluzione, l’uso della simulazione al computer per cercare di ottenere informazioni sulla soluzione, due diversi approcci per la ricerca di regolarità che aiutassero a risolvere il problema, la ricerca di conoscenze matematiche che aiutassero a dare un senso ai risultati delle simulazioni, il tentativo di spiegare alle compagne e ai compagni tutto il lungo e articolato processo di approccio al problema, che si configura come una vera e propria attività di ricerca.
Ci sono tanti modi per essere aleatori
Authors: Perrotta Anna , Rogora Enrico
Published: November 2022

Possiamo immaginare dei criteri che ci aiutino a distinguere sequenze binarie finite generate dal lancio ripetuto di una moneta da altre immaginate da un agente umano o simulate con una calcolatrice che usa un algoritmo deterministico? Si possono individuare proprietà caratteristiche delle sequenze delle diverse classi considerate?Intorno a queste domande abbiamo costruito un percorso, proposto in una classe terza di liceo scientifico, che ha stimolato gli alunni a riflettere criticamente sulle loro convinzioni relative alla probabilità e al caso.
STUDY OF WILDLIFE SPECIES WEALTH USING CAMERA TRAP IN SIPURAK HOOK AREA KERINCI SEBLAT NATIONAL PARK AREA
Authors: Pahlevi Farhan Reza , Susatya Agus , Suhartoyo Hery
Published: November 2022

Indonesia is known as one of the countries with the highest biodiversity in the world, this research was carried out from November 2020 to January 2021 in the Sipurak area, Merangin district, Jambi province. Camera traps are installed on tree trunks with an average height of 30 - 45 cm above the ground, the camera position is facing the path at a distance of 2.5 meters from the edge of the path and calculates the direction of light coming. The results of this study found 20 species of wild animals from 13 families, with a total of 201 independent event (IE) photos with the highest relative abundance of animals, namely, (Tupai javanica) of 12.95% and the lowest animal of Sumatran tiger (Panthera tigris sumatrae) by 0.72%.
Grass-weed challenges, herbicide resistance status and weed control practices across crop establishment systems in Ireland’s mild Atlantic climate
Authors: Vijayarajan Vijaya Bhaskar Alwarnaidu , Fealy Reamonn M. , Cook Sarah K. , Onkokesung Nawaporn , Barth Susanne , Hennessy Michael , Forristal Patrick D.
Published: November 2022

The challenges of grass-weed control in a mild Atlantic climate, added to by the use of non-inversion tillage and limited herbicide options necessitated on-farm knowledge acquisition on grass weeds in Ireland. We surveyed 103 farms from 2020 to 2021 of which, 62 were plough-based and 41 non-inversion tillage. The survey comprised a questionnaire to determine grower demographics, grass-weed challenges, and the adoption of integrated grass-weed control methods (IWM); a grid-square assessment of key grass weeds encountered in one or more cereal fields in both years using weed scores from 0 (absent) to 10 (total weed cover); with samples collected for herbicide-resistance testing. Across the 103 farms, Bromus spp., (62%) and Avena fatua (56%) were the most prevalent but with moderate resistance (8% acetolactate synthase (ALS)-resistant Bromus, 10% acetyl-CoA carboxylase (ACCase)-resistant A. fatua); Lolium multiflorum (13%) and Alopecurus myosuroides (16%) were found on fewer farms but with higher resistance levels (56% ACCase and/or ALS-resistant L. multiflorum, 43% ACCase/ALS-resistant A. myosuroides). Of those who adopted non-inversion tillage, a higher proportion of growers practiced crop rotation (88% cereal/non-cereal break or 83% alternate spring/winter-sown) and used cover crops (71%) than those ploughing (52-66% crop rotation or 19% cover crops), but herbicide use was similar in both systems. Despite higher levels of IWM practices, non-inversion tillage farms had higher weed scores (2.2 ± 0.2 or 3.8 ± 0.7) of B. sterilis and L. multiflorum than ploughing (1.2 ± 0.2 or 2.0 ± 0.7). Considering the complex resistance profile of high resistance-risk species, there is a need for urgent determination of and adoption of effective IWM across systems, specifically, non-inversion tillage. Most of the growers were aware of herbicide-resistant grass weeds (>80%) and most (>90%) used IWM practices (4 or more) to some extent. In our survey, non-inversion tillage farms tended to have younger growers with more formal education and larger farms. This is the first multi-component survey in Ireland establishing long-term monitoring of grass-weed challenges, grower characteristics and IWM practices.
Cell senescence alters responses of porcine trabecular meshwork cells to shear stress
Authors: Du Ruotian , Li Dongyan , Zhu Meng , Zheng Lisha , Ren Keli , Han Dong , Li Long , Ji Jing , Fan Yubo
Published: November 2022

Mechanical microenvironment and cellular senescence of trabecular meshwork cells (TMCs) are suspected to play a vital role in primary open-angle glaucoma pathogenesis. However, central questions remain about the effect of shear stress on TMCs and how aging affects this process. We have investigated the effect of shear stress on the biomechanical properties and extracellular matrix regulation of normal and senescent TMCs. We found a more significant promotion of Fctin formation, a more obvious realignment of F-actin fibers, and a more remarkable increase in the stiffness of normal cells in response to the shear stress, in comparison with that of senescent cells. Further, as compared to normal cells, senescent cells show a reduced extracellular matrix turnover after shear stress stimulation, which might be attributed to the different phosphorylation levels of the extracellular signal-regulated kinase. Our results suggest that TMCs are able to sense and respond to the shear stress and cellular senescence undermines the mechanobiological response, which may lead to progressive failure of cellular TM function with age.
Morphine-mediated release of astrocyte-derived extracellular vesicle miR-23a induces loss of pericyte coverage at the blood-brain barrier: Implications for neuroinflammation
Authors: Liao Ke , Niu Fang , Hu Guoku , Buch Shilpa
Published: November 2022

Opioids such as morphine are the most potent and efficacious drugs currently available for pain management. Paradoxically, opioids have also been implicated in inducing neuroinflammation and associated neurocognitive decline. Pericytes, a critical component of the neurovascular unit (NVU), are centrally positioned between endothelial cells and astrocytes, maintaining function of the blood-brain barrier (BBB) nd regulating neuroinflammation by controlling monocyte influx under various pathological conditions. The role of pericytes in morphine-mediated neuroinflammation however, has received less attention, especially in the context of how pericytes crosstalk with other central nervous system (CNS) cells. The current study was undertaken to examine the effect of miRNAs released from morphine-stimulated human primary astrocyte-derived extracellular vesicles (morphine-ADEVs) in mediating pericyte loss at the blood-brain barrier, leading, in turn, to increased influx of peripheral monocytes. Our findings suggest that the heterogeneous nuclear ribonucleoprotein complex A2/B1 (hnRNP A2/B1) plays role in morphine-mediated upregulation and release of miR-23a in ADEVs, and through action of morphine via mu opioid receptor.We further demonstrated that miR-23a in morphine-ADEVs could be taken up by pericytes, resulting in downregulation of PTEN expression, ultimately leading to increased pericyte migration. Furthermore, both overexpression of PTEN and blocking the miR-23a target site at PTEN 3UTR (by transfecting miR-23a-PTEN target protector), attenuated morphine-ADEV-mediated pericyte migration. We also demonstrated that in the microvessels isolated from morphine-administered mice, there were fewer PDGFβR + pericytes co-localizing with CD31+ brain endothelial cells compared with those from saline mice. In line with these findings, we also observed increased loss of pericytes and a concomitantly increased influx of monocytes in the brains of morphine-administered pericyte-labeled NG2-DsRed mice compared with saline mice. In conclusion, our findings indicate morphine-ADEVs mediated loss of pericyte coverage at the brain endothelium, thereby increasing the influx of peripheral monocytes in the central nervous system, leading to neuroinflammation.
Do we need to change our perspective about gut biomarkers? A public data mining approach to identify differentially abundant bacteria in intestinal inflammatory diseases
Authors: Vega Laura , Bohórquez Laura , Ramírez Juan David , Muñoz Marina
Published: November 2022

Introduction

The gut microbiome is involved in multiple processes that influence host physiology, and therefore, disruptions in microbiome homeostasis have been linked to diseases or secondary infections. Given the importance of the microbiome and the communities of microorganisms that compose it (microbiota), the term biomarkers were coined, which are bacteria correlated with disease states, diets, and the lifestyle of the host. However, a large field in the study of intestinal biomarkers remains unexplored because the bacterial communities associated with a given disease state have not been exactly defined yet.

Methods

Here, we analyzed public data of studies focused on describing the intestinal microbiota of patients with some intestinal inflammatory diseases together with their respective controls. With these analyses, we aimed to identify differentially abundant bacteria between the subjects with the disease and their controls.

Results

We found that frequently reported bacteria such as Fusobacterium, Streptococcus, and Escherichia/Shigella were differentially abundant between the groups, with a higher abundance mostly in patients with the disease in contrast with their controls. On the other hand, we also identified potentially beneficial bacteria such as Faecalibacterium and Phascolarctobacterium, with a higher abundance in control patients.

Discussion

Our results of the differentially abundant bacteria contrast with what was already reported in previous studies on certain inflammatory diseases, but we highlight the importance of considering more comprehensive approaches to redefine or expand the definition of biomarkers. For instance, the intra-taxa diversity within a bacterial community must be considered, as well as environmental and genetic factors of the host, and even consider a functional validation of these biomarkers through in vivo and in vitro approaches. With the above, these key bacterial communities in the intestinal microbiota may have potential as next-generation probiotics or may be functional for the design of specific therapies in certain intestinal diseases.
Metagenomic next-generation sequencing clinches the diagnosis of Legionella pneumonia in a patient with acute myeloid leukemia: A case report and literature review
Authors: Niu Siqiang , Zhao Limin
Published: November 2022

Legionella pneumonia caused by Legionella pneumophila is a multi-system disease that is a life-threatening, acute, and severe form of pneumonia. L. pneumophila is widespread and the clinical manifestations of Legionella pneumonia are similar to those of typical and atypical pneumonia. Current diagnostic scores and radiologic evidence have limited diagnostic value. Thus, it is likely that many cases of Legionella pneumonia remain unreported. We describe a woman with a medical history of acute myeloid leukemia who suffered from repeated fever, and no relief following initial empirical antibiotic treatment. Ultimately, she was diagnosed with Legionella pneumonia based on metagenomic next-generation sequencing (mNGS). We also performed a systematic review of the literature and identified 5 other patients who were diagnosed with Legionella pneumonia using mNGS, and reviewed their clinical characteristics, biological characteristics, epidemiological features, laboratory results, clinical findings, and treatments. This literature review showed that accurate etiological diagnosis is becoming increasingly essential for a definitive diagnosis and treatment strategies. The clinical manifestations of Legionella pneumonia are non-specific, and many routine laboratory diagnostic tests cannot identify Legionella. mNGS, an indispensable approach for identifying microorganisms, can provide a promising tool for the rapid and accurate etiological diagnosis methods contributing to early diagnosis, early treatment, and improved prognosis, especially for uncommon species such as L. pneumophila.
Mitral annular calcification in patients with significant mitral valve disease: An old problem with new solutions
Authors: Ascione Guido , Denti Paolo
Published: November 2022

Mitral annular calcification (MAC) is a chronic process involving mitral valve annulus, linked with an increased cardiovascular mortality and morbidity. Since its first autoptic description, a progressive evolution in diagnostic tools brought cardiac computed tomography (CT) scan to become the gold standard in MAC detection and classification. The treatment of significant mitral valve disease in patients with annular calcifications has always represented an issue for cardiac surgeons, being it linked with an increased risk of atrioventricular groove rupture, circumflex artery injury, or embolism. As a consequence, different surgical techniques have been developed over time in order to reduce the incidence of these fearsome complications. Recently, transcatheter mitral valve replacement (TMVR) has emerged as a valid alternative to surgery in high-risk patients. Both hybrid transatrial, transfemoral, or transapical approaches have been described to deliver balloon-expandable or self-expanding aortic transcatheter valves into the calcified annulus, with conflicting early and long-term results. Tendyne (Abbott Structural Heart, Santa Clara, CA, USA) is a promising transapical-delivered option. Early results have shown effectiveness and safety of this device in patients with MAC and severe mitral valve disease, with the lowest rate of embolization, mortality, and left ventricular outflow tract obstruction (LVOTO) reported so far.
Narrative update of clinical trials with antihypertensive drugs in children and adolescents
Authors: Redon Josep , Seeman Tomas , Pall Dénes , Suurorg Lagle , Kamperis Konstantinos , Erdine Serap , Wühl Elke , Mancia Giuseppe
Published: November 2022

Introduction

To date, our knowledge on antihypertensive pharmacological treatment in children and adolescents is still limited because there are few randomized clinical trials (CTs), hampering appropriate management. The objective was to perform a narrative review of the most relevant aspects of clinical trials carried out in primary and secondary hypertension.

Methods

Studies published in PubMed with the following descriptors: clinical trial, antihypertensive drug, children, adolescents were selected. A previous Cochrane review of 21 randomized CTs pointed out the difficulty that statistical analysis could not assess heterogeneity because there were not enough data. A more recent meta-analysis, that applied more stringent inclusion criteria and selected 13 CTs, also concluded that heterogeneity, small sample size, and short follow-up time, as well as the absence of studies comparing drugs of different classes, limit the utility.

Results

In the presented narrative review, including 30 studies, there is a paucity of CTs focusing only on children with primary or secondary, mainly renoparenchymal, hypertension. In trials on angiotensin converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARBs), calcium channel blockers (CCBs) and diuretics, a significant reduction of both SBP and DBP in mixed cohorts of children with primary and secondary hypertension was achieved. However, few studies assessed the effect of antihypertensive drugs on hypertensive organ damage.

Conclusions

Given the increasing prevalence and undertreatment of hypertension in this age group, innovative solutions including new design, such as ‘n-of-1', and optimizing the use of digital health technologies could provide more precise and faster information about the efficacy of each antihypertensive drug class and the potential benefits according to patient characteristics.
Plasma desmosine for prediction of outcomes after acute myocardial infarction
Authors: Ali Kashan , Israr Muhammad Zubair , Ng Leong L. , Mordi Ify , Lang Chim C. , Kuzmanova Elena , Huang Jeffrey T-J , Choy Anna-Maria
Published: November 2022

Background

Elastin degradation is implicated in the pathology of vulnerable plaque. Recent studies show promising results for plasma desmosine (pDES), an elastin-specific degradation product, as a marker of cardiovascular disease (CVD) outcomes. The aim of this study was to investigate the potential role of pDES as a marker of clinical outcome in patients with acute myocardial infarction (AMI).

Materials and methods

In this case-control study, we studied 236 AMI patients: 79 patients who had death and/or myocardial infarction (MI) at 2 years, and 157 patients who did not have an event at 2 years. pDES was measured using a validated liquid chromatography-tandem mass spectrometry method. Association of pDES with adverse outcomes, and the incremental value of pDES to global registry of acute coronary events (GRACE) score for risk stratification was assessed.

Results

pDES levels were elevated in patients with the composite outcome of death/MI at 2 years (p = 0.002). Logistic regression analyses showed pDES to be associated with death/MI at 2 years [Odds ratio (OR) 5.99 (95% CI 1.81–19.86) p = 0.003]. pDES remained a significant predictor of death/MI at 2 years even after adjustment for age, sex, history of CVD, revascularisation, blood pressure, medications on discharge, Troponin I, and NT-proBNP levels.[OR 5.60 (95% CI 1.04–30.04) p = 0.044]. In another multivariable model including adjustment for eGFR, pDES was significantly associated with the composite outcome at 6 months, but not at 2 years follow up. DES was also able to reclassify risk stratification for death/MI at 6 months, when added to the GRACE risk model [Net Reclassification Index (NRI) 41.2 (95% CI 12.0–70.4) p = 0.006].

Conclusion

pDES concentrations predict clinical outcomes in patients with AMI, demonstrating its potential role as a prognostic marker in AMI.
Adoption of electronic medical records in developing countries—A multi-state study of the Nigerian healthcare system
Authors: Akwaowo Christie Divine , Sabi Humphrey Muki , Ekpenyong Nnette , Isiguzo Chimaobi M. , Andem Nene Francis , Maduka Omosivie , Dan Emem , Umoh Edidiong , Ekpin Victory , Uzoka Faith-Michael
Published: November 2022

Electronic medical records (EMR) are extensively used in developed countries to manage patient records and facilitate consultations and follow-up of treatment. This has resulted in centralised databases where different services and clinicians can quickly access patient data to support healthcare delivery. However, adoption and usage of EMR in developing countries is not common and, in most cases, non-existent. Clinicians are dependent on patients keeping their own records manually with no centralised database to manage and control the patient medical history. The key objective of this study was to investigate the propensity of clinicians and senior management personnel in healthcare facilities to adopt EMR and evaluate the contextual factors that impact or impede adoption. Using Davis's technology adoption model extended with other factors, this study determined if contextual or situational factors are associated with barriers that impede adoption of EMRs in developing countries. Using a cross-sectional quantitative research approach, a questionnaire was designed to collect data across four states in the Niger Delta region of Nigeria. Stratified random sampling was used to select healthcare facilities that participated in the survey and selection of respondents from each healthcare facility. Data was collected by trained research assistants and a total of 1,177 valid responses were received and analysed using factor analysis and multiple regression analysis. The results from the analysis show that usefulness, critical success factors, awareness and relative advantage significantly influence clinicians' intention to adopt EMRs. Surprisingly, infrastructure availability was not statistically significant. Meanwhile, risk and data security both negatively influence adoption, indicating that user perception of risk and safety of their data decreases their propensity to adopt EMRs. The results from this study suggests that usefulness and anticipated success factors in facilitating operations within healthcare facilities have a great influence on user adoption of EMRs. Awareness, training and education of users on the effectiveness of EMRs and their usefulness will increase adoption. The results will be beneficial in helping government and healthcare leaders formulate policies that will guide and support adoption of EMR. Other policy recommendations and suggestions for future research were also proffered.
A data-driven artificial neural network model for the prediction of ground motion from induced seismicity: The case of The Geysers geothermal field
Authors: Prezioso Edoardo , Sharma Nitin , Piccialli Francesco , Convertito Vincenzo
Published: November 2022

Ground-motion models have gained foremost attention during recent years for being capable of predicting ground-motion intensity levels for future seismic scenarios. They are a key element for estimating seismic hazard and always demand timely refinement in order to improve the reliability of seismic hazard maps. In the present study, we propose a ground motion prediction model for induced earthquakes recorded in The Geysers geothermal area. We use a fully connected data-driven artificial neural network (ANN) model to fit ground motion parameters. Especially, we used data from 212 earthquakes recorded at 29 stations of the Berkeley–Geysers network between September 2009 and November 2010. The magnitude range is 1.3 and 3.3 moment magnitude (Mw), whereas the hypocentral distance range is between 0.5 and 20 km. The ground motions are predicted in terms of peak ground acceleration (PGA), peak ground velocity (PGV), and 5% damped spectral acceleration (SA) at T=0.2, 0.5, and 1 s. The predicted values from our deep learning model are compared with observed data and the predictions made by empirical ground motion prediction equations developed bySharma et al. (2013)for the same data set by using the nonlinear mixed-effect (NLME) regression technique. For validation of the approach, we compared the models on a separate data made of 25 earthquakes in the same region, with magnitudes ranging between 1.0 and 3.1 and hypocentral distances ranging between 1.2 and 15.5 km, with the ANN model providing a 3% improvement compared to the baseline GMM model. The results obtained in the present study show a moderate improvement in ground motion predictions and unravel modeling features that were not taken into account by the empirical model. The comparison is measured in terms of both theR2statistic and the total standard deviation, together with inter-event and intra-event components.
Quality management of higher education within the framework of the socio-investment model of economic growth: State audit and financial control
Authors: Yaroshchuk Anatoliy B. , Guliev Azamat Yu. , Mikhaylenko Mikhail N.
Published: November 2022

The article aims to study the contribution of quality management in higher education through state audit and financial control to the implementation of the socio-investment model of economic growth. The article is based on the scientific hypothesis that quality management in higher education should be based on university rankings. The article presents the authors’ view on the interpretation of recent results in the research field of quality management in higher education and reveals the strengths and weaknesses of the hypothesis. Systematization and critical analysis of the indicators of quality and effectiveness in higher education based on the leading university rankings for 2022—the Ministry of Education and Science of the Russian Federation—are performed. The case study method is used for the case analysis of the management of quality and effectiveness on the example of the leading Russian university, which has been the leader of these rankings for many years: Lomonosov Moscow State University (MSU). The scientific novelty and originality of the article are associated with a systematic view of the quality and effectiveness of higher education, which was first formed by the authors through a combination and grouping of indicators from the leading university rankings for 2022. The theoretical significance of the authors’ conclusions lies in the fact that the article clearly identifies a significant contribution of the quality control of education and the performance management of universities to the implementation of the socio-investment model of economic growth. The practical significance of the obtained results is that the scientific and methodological basis for monitoring and assessing quality and effectiveness in higher education based on the leading university ratings for 2022 makes it possible to improve the state audit and financial control of university activities in the implementation of the socio-investment model of economic growth.
Finnish teachers’ and students’ programming motivation and their role in teaching and learning computational thinking
Authors: Fagerlund Janne , Leino Kaisa , Kiuru Noona , Niilo-Rämä Mikko
Published: November 2022

Introduction

Despite the growing importance of teaching and learning computational thinking (CT) through programming in schools, research has shown major individual differences in teachers’ instruction emphasis and students’ skills in these topics.

Objective

This study aims to shed further light on the role that teachers’ and students’ programming motivation plays in CT.

Methods

The topic is approached from the viewpoint of the self-determination theory, which can help to understand teachers’ instruction and students’ learning. Our sample consisted of Finnish Grade 8 teachers (N = 1,853) and students (N = 2,546) who participated in the International Computer and Information Literacy Study (ICILS) in 2018. Focusing on teachers’ CT instruction emphasis, students’ CT test scores, and the Intrinsic Motivation Inventory, we investigate (1) distributions of teachers’ and students’ responses to intrinsic and extrinsic programming motivation questions, (2) associations between teachers’ and students’ programming motivation and their background factors, and (3) associations between programming motivation and teachers’ CT instruction emphasis and students’ CT test scores. The data was analyzed by examining descriptive statistics, computing mean differences and correlation coefficients and by performing (multiple) linear regression models.

Results

The results showed that teachers had high extrinsic programming motivation, but the extent of their intrinsic programming motivation varied widely based on their prior programming teaching experience, subject taught, and gender. Students, in turn, reported both high intrinsic and extrinsic motivation toward programming, but boys were generally more motivated for programming than girls. High programming motivation was moderately related to teachers’ higher CT instruction emphasis and students’ higher CT test scores.

Conclusion

The findings give a strong incentive to pay attention to increasing especially girls’ programming motivation and providing teachers with positive CT experiences relevant to their subject and with a particular objective to increase intrinsic motivation especially among teachers who lack prior programming teaching experience and interest in the topic.
Expression and structural analysis of human neuroligin 2 and neuroligin 3 implicated in autism spectrum disorders
Authors: Zhang Zhenzhen , Hou Mengzhuo , Ou Huaxing , Wang Daping , Li Zhifang , Zhang Huawei , Lu Jianping
Published: November 2022

The development of autism spectrum disorders (ASDs) involves both environmental factors such as maternal diabetes and genetic factors such as neuroligins (NLGNs). NLGN2 and NLGN3 are two members of NLGNs with distinct distributions and functions in synapse development and plasticity. The relationship between maternal diabetes and NLGNs, and the distinct working mechanisms of different NLGNs currently remain unclear. Here, we first analyzed the expression levels of NLGN2 and NLGN3 in a streptozotocin-induced ASD mouse model and different brain regions to reveal their differences and similarities. Then, cryogenic electron microscopy (cryo-EM) structures of human NLGN2 and NLGN3 were determined. The overall structures are similar to their homologs in previous reports. However, structural comparisons revealed the relative rotations of two protomers in the homodimers of NLGN2 and NLGN3. Taken together with the previously reported NLGN2–MDGA1 complex, we speculate that the distinct assembly adopted by NLGN2 and NLGN3 may affect their interactions with MDGAs. Our results provide structural insights into the potential distinct mechanisms of NLGN2 and NLGN3 implicated in the development of ASD.
The relationship between succession and reclamation of desertified areas in artificial forests of Calligonum spp. in an arid desert of southeastern Iran
Authors: Ebrahimi Mahdieh , Saberi Morteza
Published: November 2022

This research investigates the association between the succession and restoration of degraded land in the southeast of Iran with artificialCalligonumforests regarding vegetation changes, soil properties, carbon (C) and nitrogen (N) pools in vegetation and soil. Eight forestry sites were selected, aged 1, 4, 6, 9, 11, 16, 25, and 30 years. Observations indicated that vegetation percentage, density, frequency, richness, and diversity of species substantially increased (p< 0.01). The highest percentage of vegetation (80.30%), density (62.70 n ha−1), richness (14.15), and diversity (0.90) was observed in the 30-year site. At the end of the succession phase under study (the 25- and 30-year sites), the variation trend of vegetation was steady. As the age of the forests increased, the soil nutrient values increased significantly during succession (p< 0.01), even though acidity and electrical conductivity (EC) did not change significantly over time (p> 0.01). In the early stages of succession, the soil’s C and N pools (aerial biomass, root, and litter) did not increase significantly (p> 0.01). Over time, however, C and N pools of the soil and plants increased (the highest amounts were seen in the 30-year site). The results indicated a significant difference in the soil and vegetation properties in the forestry sites. In general, planting native species and the succession of vegetation can play an effective role in preserving the environment in degraded lands and increasing the C and N pools.
A depth-first search algorithm for oligonucleotide design in gene assembly
Authors: Liang Hanjie , Chen Zengrui , Fang Gang
Published: November 2022

When synthesizing a gene with a long DNA sequence, it is usually necessary to divide it into several fragments. Based on these fragments, a set of oligonucleotides for gene assembly is produced. Each oligonucleotide is synthesized separately by the chemical reaction, and then the obtained oligonucleotides are assembled into the full gene sequence, in a specific environment, by polymerase chain reaction (PCR) or ligase chain reaction (LCR). In this paper, an effective and efficient algorithm to divide long genes into oligonucleotide sets is presented. First, according to the length of the overlapping oligonucleotide region, the long DNA sequence to be synthesized is divided into fragments of approximately equal length. Second, the length of these fragments is iterated to dynamically optimize the length of the overlapping regions to reduce melting temperature fluctuations. Then, the improved depth-first search algorithm is used according to the design principle of pruning optimization to obtain a uniform set of oligonucleotides with very close melting temperatures. This will decrease the errors in gene assembly with PCR or LCR. Lastly, the oligonucleotides that have homologous melting temperatures needed for PCR-based synthesis and two-step assembly of the target gene are deduced and outputted.
Identification of a novel AIFM1 variant from a Chinese family with auditory neuropathy
Authors: Wang Rongrong , Bai Xiaohui , Yang Huiming , Ma Jingyu , Yu Shudong , Lu Zhiming
Published: November 2022

Background: Auditory neuropathy (AN) is a specific type of hearing loss characterized by impaired language comprehension. Apoptosis inducing factor mitochondrion associated 1 (AIFM1) is the most common gene associated with late-onset AN. In this study, we aimed to screen the pathogenic variant of AIFM1 in a Chinese family with AN and to explore the molecular mechanism underlying the function of such variant in the development of AN.

Methods: One patient with AN and eight unaffected individuals from a Chinese family were enrolled in this study. A comprehensive clinical evaluation was performed on all participants. A targeted next-generation sequencing (NGS) analysis of a total of 406 known deafness genes was performed to screen the potential pathogenic variants in the proband. Sanger sequencing was used to confirm the variants identified in all participants. The pathogenicity of variant was predicted by bioinformatics analysis. Immunofluorescence and Western blot analyses were performed to evaluate the subcellular distribution and expression of the wild type (WT) and mutant AIFM1 proteins. Cell apoptosis was evaluated based on the TUNEL analyses.

Results: Based on the clinical evaluations, the proband in this family was diagnosed with AN. The results of NGS and Sanger sequencing showed that a novel missense mutation of AIFM1, i.e., c.1367A > G (p. D456G), was identified in this family. Bioinformatics analysis indicated that this variant was pathogenic. Functional analysis showed that in comparison with the WT, the mutation c.1367A > G of AIFM1 showed no effect on its subcellular localization and the ability to induce apoptosis, but changed its protein expression level.

Conclusion: A novel variant of AIFM1 was identified for the first time, which was probably the genetic cause of AN in a Chinese family with AN.
Circulating tumour cell combined with DNA methylation for early detection of hepatocellular carcinoma
Authors: Liang Wenjin , Xu Zhigao , Kong Fangyu , Huang Xiao , Xiao Yuxin , Zhou Wei , Ye Shaojun , Ye Qifa
Published: November 2022

Background: The inadequate early detection strategies makes hepatocellular carcinoma (HCC) patients with poor prognisis. Therefore, more effective detection methods are urgently needed for early detection and early intervention of HCC.

Methods: 17 cases of suspected HCC patients and 11 cases of HBV-related decompensated cirrhosis (HBV-DeCi) patients were enrolled. For each patient, 5 ml blood sample was separated into circulating tumor cells (CTCs) and plasma, CTCs were stained with Diff staining for counting. Plasma was used for extracting cell free DNA (cfDNA) and then analyzed by qMSP assay. Ct values were recorded for GNB4 and Riplet as target genes and β-actin as an endogenous reference gene. Finally, clinical efficacy of CTC count combined with GNB4/Riplet methylation detection for early diagnosis of HCC was analyzed.

Results: The CTC of HCC patients has pleomorphic characteristics, but it is difficult to distinguish from other blood cells with non-obviously pleomorphic of CTC. Although a small number of CTCs can also be detected in HBV-DeCi patients (control group), the number is significantly lower than that in HCC patients, the sensitivity and specificity of CTC for HCC detection were 70.6% and 90.9% (AUC = 0.81). The Ct values of GNB4 and Riplet methylation were significantly different between HCC patients and control group patients. When CTC combined with two genes, the AUC value was significantly increased to 0.98, the sensitivity was 88.2%, and the specificity was 100%.

Conclusion: Our study has developed a novel test that CTC count combined with GNB4/Riplet methylation detection and showed its high performance for early diagnosis of HCC.
High-content CRISPR screening in tumor immunology
Authors: Holcomb Erin A. , Pearson Ashley  N. , Jungles Kassidy M. , Tate Akshay , James Jadyn , Jiang Long , Huber Amanda  K. , Green Michael D.
Published: November 2022

CRISPR screening is a powerful tool that links specific genetic alterations to corresponding phenotypes, thus allowing for high-throughput identification of novel gene functions. Pooled CRISPR screens have enabled discovery of innate and adaptive immune response regulators in the setting of viral infection and cancer. Emerging methods couple pooled CRISPR screens with parallel high-content readouts at the transcriptomic, epigenetic, proteomic, and optical levels. These approaches are illuminating cancer immune evasion mechanisms as well as nominating novel targets that augment T cell activation, increase T cell infiltration into tumors, and promote enhanced T cell cytotoxicity. This review details recent methodological advances in high-content CRISPR screens and highlights the impact this technology is having on tumor immunology.
Molecular subtypes and a prognostic model for hepatocellular carcinoma based on immune- and immunogenic cell death-related lncRNAs
Authors: He Mingang , Gu Wenchao , Gao Yang , Liu Ying , Liu Jie , Li Zengjun
Published: November 2022

Background

Accumulating evidence shows that immunogenic cell death (ICD) enhances immunotherapy effectiveness. In this study, we aimed to develop a prognostic model combining ICD, immunity, and long non-coding RNA biomarkers for predicting hepatocellular carcinoma (HCC) outcomes.

Methods

Immune- and immunogenic cell death-related lncRNAs (IICDLs) were identified from The Cancer Genome Atlas and Ensembl databases. IICDLs were extracted based on the results of differential expression and univariate Cox analyses and used to generate molecular subtypes using ConsensusClusterPlus. We created a prognostic signature based on IICDLs and a nomogram based on risk scores. Clinical characteristics, immune landscapes, immune checkpoint blocking (ICB) responses, stemness, and chemotherapy responses were also analyzed for different molecular subtypes and risk groups.

Result

A total of 81 IICDLs were identified, 20 of which were significantly associated with overall survival (OS) in patients with HCC. Cluster analysis divided patients with HCC into two distinct molecular subtypes (C1 and C2), with patients in C1 having a shorter survival time than those in C2. Four IICDLs (TMEM220-AS1, LINC02362, LINC01554, and LINC02499) were selected to develop a prognostic model that was an independent prognostic factor of HCC outcomes. C1 and the high-risk group had worse OS (hazard ratio > 1.5, p < 0.01), higher T stage (p < 0.05), higher clinical stage (p < 0.05), higher pathological grade (p < 0.05), low immune cell infiltration (CD4+ T cells, B cells, macrophages, neutrophils, and myeloid dendritic cells), low immune checkpoint gene expression, poor response to ICB therapy, and high stemness. Different molecular subtypes and risk groups showed significantly different responses to several chemotherapy drugs, such as doxorubicin (p < 0.001), 5-fluorouracil (p < 0.001), gemcitabine (p < 0.001), and sorafenib (p < 0.01).

Conclusion

Our study identified molecular subtypes and a prognostic signature based on IICDLs that could help predict the clinical prognosis and treatment response in patients with HCC.
Early vascular endothelial complications after hematopoietic cell transplantation: Role of the endotheliopathy in biomarkers and target therapies development
Authors: Moreno-Castaño Ana Belén , Salas María Queralt , Palomo Marta , Martinez-Sanchez Julia , Rovira Montserrat , Fernández-Avilés Francesc , Martínez Carmen , Cid Joan , Castro Pedro , Escolar Gines , Carreras Enric , Diaz-Ricart Maribel
Published: November 2022

This work aims to review the role of endothelial dysfunction underlying the main complications appearing early after autologous and allogeneic hematopoietic cell transplantation (HCT). The endothelial damage as the pathophysiological substrate of sinusoidal obstruction syndrome (SOS) is well established. However, there is growing evidence of the involvement of endothelial dysfunction in other complications, such as acute graft-versus-host disease (aGVHD) and transplant-associated thrombotic microangiopathy (TA-TMAs). Moreover, HCT-related endotheliopathy is not only limited to the HCT setting, as there is increasing evidence of its implication in complications derived from other cellular therapies. We also review the incidence and the risk factors of the main HCT complications and the biological evidence of the endothelial involvement and other linked pathways in their development. In addition, we cover the state of the art regarding the potential use of the biomarkers of endotheliopathy in the prediction, the early diagnosis, and the follow-up of the HCT complications and summarize current knowledge points to the endothelium and the other linked pathways described as potential targets for the prevention and treatment of HCT-complications. Lastly, the endothelium-focused therapeutic strategies that are emerging and might have a potential impact on the survival and quality of life of post-HCT-patients are additionally reviewed.
Cholesterol: An important actor on the cancer immune scene
Authors: Halimi Hossein , Farjadian Shirin
Published: November 2022

Based on the structural and signaling roles of cholesterol, which are necessary for immune cell activity, high concentrations of cholesterol and its metabolites not only trigger malignant cell activities but also impede immune responses against cancer cells. To proliferate and evade immune responses, tumor cells overcome environmental restrictions by changing their metabolic and signaling pathways. Overexpression of mevalonate pathway enzymes and low-density lipoprotein receptor cause elevated cholesterol synthesis and uptake, respectively. Accordingly, cholesterol can be considered as both a cause and an effect of cancer. Variations in the effects of blood cholesterol levels on the outcome of different types of cancer may depend on the stage of cancer. However, positive effects of cholesterol-lowering drugs have been reported in the treatment of patients with some malignancies.
Identification of immune cell function in breast cancer by integrating multiple single-cell data
Authors: Zhang Liyuan , Qin Qiyuan , Xu Chen , Zhang Ningyi , Zhao Tianyi
Published: November 2022

Breast cancer has now become the most commonly diagnosed cancer worldwide. It is a highly complex and heterogeneous disease that comprises distinct histological features and treatment response. With the development of molecular biology and immunology, immunotherapy has become a new field of breast cancer treatment. Identifying cell-type-specific genes critical to the immune microenvironment contributes to breast cancer treatment. Single-cell RNA sequencing (scRNA-seq) technology could serve as a powerful tool to analyze cellular genetic information at single-cell resolution and to uncover the gene expression status of each cell, thus allowing comprehensive assessment of intercellular heterogeneity. Because of the influence of sample size and sequencing depth, the specificity of genes in different cell types for breast cancer cannot be fully revealed. Therefore, the present study integrated two public breast cancer scRNA-seq datasets aiming to investigate the functions of different type of immune cells in tumor microenvironment. We identified total five significant differential expressed genes of B cells, T cells and macrophage and explored their functions and immune mechanisms in breast cancer. Finally, we performed functional annotation analyses using the top fifteen differentially expressed genes in each immune cell type to discover the immune-related pathways and gene ontology (GO) terms.
Functional molecular expression of nature killer cells correlated to HBsAg clearance in HBeAg-positive chronic hepatitis B patients during PEG-IFN α-2a therapy
Authors: Cao Weihua , Lu Huihui , Zhang Luxue , Wang Shiyu , Deng Wen , Jiang Tingting , Lin Yanjie , Yang Liu , Bi Xiaoyue , Lu Yao , Zhang Lu , Shen Ge , Liu Ruyu , Chang Min , Wu Shuling , Gao Yuanjiao , Hao Hongxiao , Xu Mengjiao , Chen Xiaoxue , Hu Leiping , Xie Yao , Li Minghui
Published: November 2022

Objective

To explore whether the frequencies and functional molecules expression of Natural Killer cells (NK cells) are related to hepatitis B surface antigen (HBsAg) disappearance in hepatitis B e envelope antigen (HBeAg)-positive patients with chronic hepatitis B (CHB) throughout peginterferon alpha-2a (PEG-IFN α-2a) treatment.

Methods

In this prospective research, HBeAg-positive patients with CHB received PEG-IFN α-2a treatment, completing 4-year follow-up. After PEG-IFN α-2a treatment, undetectable HBV DNA, HBsAg loss, and HBeAg disappearance were defined as functional cure. Proportions of NK, CD56dim, CD56bright, NKp46+, NKp46dim, NKp46high, and interferon alpha receptor 2 (IFNAR2)+ NK cells, and the mean fluorescence intensity (MFI) of NK cell surface receptors IFNAR2 and NKp46 were detected.

Results

66 patients were enrolled into the study in which 17 patients obtained functional cure. At baseline, hepatitis B virus desoxyribose nucleic acid (HBV DNA) titer in patients with functional cure was remarkably lower than that in Non-functional cure group. Compared with baseline, HBV DNA levels, HBsAg levels, and HBeAg levels significantly declined at week 12 and 24 of therapy in patients with functional cure. At baseline, the negative correlation between CD56bright NK% and HBV DNA and the negative correlation between CD56dim NK% and HBV DNA was showed; CD56bright NK% and IFNAR2 MFI in patients with functional cure were remarkably higher than those in patients without functional cure. After therapy, CD56bright NK% and NKp46high NK% in patients with functional cure were higher than those in patients without functional cure. In Functional cure group, after 24 weeks of treatment NK%, CD56bright NK%, IFNAR2 MFI weakly increased, and NKp46high NK% and NKp46 MFI significantly increased, meanwhile, CD56dim NK% and NKp46dim NK% decreased. Only NKp46 MFI increased after therapy in patients without functional cure.

Conclusion

The lower HBV DNA load and the higher CD56bright NK% before therapy, and the higher the post-treatment CD56bright NK%, IFNAR2 MFI, NKp46high NK%, the easier to achieve functional cure.