bluuebunny/crossref_metadata_2025 huggingface dataset:
Educação
Authors: Paes de Barros Rafael
Published: April 2022

O presente artigo discorre acerca da repartição de competências dos entes federativos e respectiva competência de oferta do ensino público. A partir da Constituição Federal de 1988 que regula a base do ordenamento jurídico brasileiro e organiza a atuação do estado perante a sua população. Neste sentido, a constituição brasileira prevê a educação como um direito de todos e dever do estado e da família. Por conta disso, o objetivo deste trabalho é apresentar a relação entre a repartição de competência da educação e a oferta da educação na esfera pública nos níveis fundamental I e II, médio e superior. A metodologia adotada é uma pesquisa documental com a base na Constituição Federal de 1988 e legislação extravagante sobre a educação aliada a uma revisão de literatura. Por fim, conclui-se que a legislação vigente prevê a divisão de oferta do ensino público prioritariamente para a união na oferta de ensino superior, para o estado na oferta de ensino médio e fundamental II e para o município a oferta do ensino fundamental I.
Guest Editorial: Aging US Shale Wells: Years of Remaining Opportunities or Growing Asset Retirement Obligations?
Authors: Freeman Laura
Published: April 2022

A year ago, I wrote a JPT Guest Editorial on stripper wells in the US. It was the result of data analysis that I personally found shocking and the result of frustration I was having with clients looking for acquisitions at that time.

The piece was written right before oil prices started an incredible climb and when natural gas prices had been under $3.00/Mcf for an extended period. On the acquisition and divestiture front, although corporate consolidation was ongoing, deal counts were at a decade low, and it was extremely hard to transact. With oil prices at $45/bbl and the so-called “shale bust” of the past few years, many investors would not even consider an unconventional asset.

Given this backdrop, I had clients on the hunt for conventional assets with stable base cash flow and limited risk. One client was a very serious buyer; however, some decision makers were adamant about certain asset characteristics, namely conventional, onshore US, certain states, operated working interest, proved producing (PDP), and no stripper wells. Despite this seeming like a reasonable set of criteria, asset after asset kept getting screened out. Finally, I had a call with the CFO and in frustration told him, “They’re all stripper wells.”

Something about saying that out loud stuck in my head and got me thinking. I started wondering “how many stripper wells are there?” I began to think about the well count across the US, well IPs (initial production or starting flow rates), and the approximate rates at which I generally saw most wells go uneconomic in financial modeling. Given about 1 million active wells in the US, it seemed like there ought to be a decent percentage of active, producing, conventional wells over the 20–30 BOPD mark. I started pulling well data and found that for many US regions, 95% or more of the active vertical wells were producing 15 BOPD or less.

The article generated a lot of interest as it brought to light something many people think is a problem in the back of their mind but had not seen quantified in a simple way. The follow-up question I got over and over was “What about horizontal wells?”

The US Energy Information Administration (EIA) estimates that about 80% of US oil and gas wells are producing less than 15 BOEPD. For horizontal wells, EIA estimates about half are 50 BOEPD or less (the use of 6:1 BOE tends to improve the overall daily rate in an amount that is disproportionate to the value and economic impact of adding the gas stream). This rate includes both conventional and unconventional wells. It is natural to assume that the older conventional wells bring down the average and that more recent production from the hottest US shale plays is much higher.
Distributed Fiber-Optic Sensing Enhances Flow Diagnostics in Gas Condensate Well
Authors: Carpenter Chris
Published: April 2022

This article, written by JPT Technology Editor Chris Carpenter, contains highlights of paper SPE 205435, “Flow Diagnostics in High-Rate Gas Condensate Well Using Distributed Fiber-Optic Sensing and Its Validation With Conventional Production Log,” by Fuad Aziz Atakishiyev, SPE, BP, and Alessandro Delfino and Cagri Cerrahoglu, Lytt, et al. The paper has not been peer reviewed.

The authors describe a machine-learning (ML) approach for processing distributed-fiber-optic-sensing (DFOS) data that enables dynamic flow-profile monitoring using a fiber-optic electric-line cable deployed in a gas condensate well and compare the method with a conventional approach. DFOS technology has the potential to provide more-efficient and dynamic flow profiles compared with traditional methods, particularly in high-rate gas wells where production logs (PL) are recorded at reduced rates to avoid tool lifting.

Technology and Field Introduction

DFOS surface acquisition systems launch short pulses of light into an optical fiber, then receive its backscatter and convert it into physical measurements: temperature in the case of distributed temperature sensing (DTS) and acoustic intensity in the case of distributed acoustic sensing (DAS). These systems essentially turn a fiber-optic cable into a long array of thermometers (DTS) or multifrequency microphones (DAS). The DFOS systems record the backscatter signal continuously and measure at multiple points along the fiber. The major advantage of DFOS acquisition is the ability to record data throughout time at a very high sampling frequency.

Unlike traditional PL tools, insights provided by DFOS offer a real-time view of changes in production without intervention.

A successful trial was performed in a high-rate gas-producing well to test the quantitative inflow profiling algorithm on DFOS data. As part of the work, conventional PL data were acquired in high-rate gas production Well A01. An electric-line cable with built-in multimode and single-mode fiber-optic line was used to acquire conventional PL data. DAS and DTS data were acquired simultaneously for approximately 30 minutes while the well produced at a gas rate of approximately 70 MMscf/D.

No sand-control completions were planned for Well A01 or for other wells in the field; therefore, in addition to the identification of a quantitative inflow profile, another main objective of the study was to identify intervals with sand production.
Damage Potential, Proppant-Transport Traits of High-Viscosity Friction Reducers
Authors: Carpenter Chris
Published: April 2022

This article, written by JPT Technology Editor Chris Carpenter, contains highlights of paper SPE 199736, “High-Viscosity Friction Reducers: Potential for Fracture Damage and Impact of Brines on Proppant-Transport Capability,” by Barry Hlidek, SPE, and Robert Duenckel, SPE, Stim-Lab. The paper has not been peer reviewed.

High-viscosity friction reducer (HVFR) fracturing fluids are used widely for unconventional reservoir development. HVFRs are easy to apply and can reduce chemical costs. The objective of the study described in the complete paper is to measure polymer cleanup in both propped and unpropped fractures using multiple methods. Additionally, the study compares rheological measurements in proppant-transport observations in brines using a large-scale slot-flow device.

Potential for Formation Damage

High-polymer-concentration crosslinked fracturing-fluid systems often have been supplanted by linear (i.e., noncrosslinked) guar systems of lower-polymer loading (e.g. 20 lbm/1,000 gal or less) or slickwater systems often thought to be nondamaging. Recently, HVFRs have been used regularly not only to provide friction reduction during pumping of the fracture stimulation but also to offer some degree of proppant transport. These usually are polyacrylamides with concentrations of 2–3 gal/1,000 gal, but concentrations may be as high as 6 gal/1,000 gal. The potential for damage from these HVFRs is the subject of the authors’ study. The complete paper discusses evaluation of proppant-pack damage in conventional reservoirs as well, but this synopsis will focus on evaluation of proppant-pack damage in unconventional reservoirs.
Utilizing Thermally Controlled Fluid to Improve Cluster Uniformity and Efficiency
Authors: Almarri Misfer J. , AlTammar Murtadha J. , Fowler Garrett , Alruwaili Khalid M.
Published: April 2022

This paper investigates how thermoelasticity effects may impact cluster stimulation uniformity and fracture initiation and growth in horizontal, multifractured laterals. Thermal cooling has been previously shown to lower the minimum principal stress and induce fracturing in conventional reservoirs. In the current study, cool fluid is injected prior to the primary stimulation to investigate whether local minimum principal stress can be reduced. In the base case without pre-treatment, fractures are propagated in non-uniform manner after the primary stimulation. This results in few clusters being the dominant ones leaving the rest of the reservoir’s hydrocarbon unstimulated. The pre-treatment period can be utilized to reduce the in-situ stress at the entry of the clusters. Simulation results show that clusters with a pre-cooling period have more uniform fractures compared to the base case. Utilizing thermally controlled fluid is a novel method for improving cluster uniformity and efficiency.
The value of preoperative nutritional status, the systemic inflammation index and a nomogram for the prognosis of patients with esophageal cancer after radical resection
Authors: Wang Huike , Yang Yalan , Meng Xiangrui , Luo Xi , Wang Feng
Published: April 2022

Background
Controlling nutritional status (CONUT), prognostic nutritional index (PNI), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) are new parameters that reflect the immune-nutritional status in some cancers.
Purpose
To investigate the relationship between preoperative nutritional status and systemic inflammatory indexes on the clinicopathological prognosis of patients with stage I-IV esophageal cancer and to clarify the predictive value of nutritional status and inflammatory indexes on tumor recurrence, metastasis and long-term survival after radical resection.
Methods
The clinical data of 381 patients who underwent radical esophagectomy at the First Affiliated Hospital of Zhengzhou University from August 5, 2013, to August 1, 2021, were analyzed retrospectively. The preoperative clinical characteristics and hematological examination results were collected, the data on nutritional and immune status were analyzed, tumor recurrence and survival were evaluated by telephone follow-up, and overall survival (OS) and progression-free survival (PFS) were calculated. Nutritional data and the immune status, clinical data and survival information were also analyzed.
Results
Analysis of the clinical data of 381 patients with esophageal cancer undergoing radical esophagectomy revealed that preoperative nutritional status was related to preoperative complications, neoadjuvant therapy, TNM stage, tumor location, pathological type, vascular invasion, nerve invasion and regional lymph node metastasis, and the indexes of systemic inflammation were related to neoadjuvant therapy, TNM stage, tumor location, pathological type and nerve invasion. In univariate analysis, vascular invasion, preoperative CONUT, PNI and SII were identified as important factors affecting prognosis. In multivariate analysis, vascular invasion, preoperative CONUT, PNI, and SII were identified as important factors showing an independent correlation with survival time. A nomogram was developed, and the statistically significant influencing factors from the multivariate Cox regression model were included to predict the 2-, 3- and 5-year overall survival rates of patients with lung metastasis from gastric cancer.
Conclusion
CONUT, PNI and SII are independent risk factors for predicting overall survival and recurrence-free survival after radical resection of esophageal cancer. The proposed nomogram prediction model can aid in individualized analysis of the prognosis of these patients.
Novel Source for Tooth Regeneration: Human induced Pluripotent Stem Cells derived Odontogenic Mesenchymal Stem Cells
Authors: Kim Ji-Hye , Yang Jihye , Ki Min-Gi , Jeon Dae Hyun , Kim Jae-Won , Jang Mi , Lee Gene
Published: April 2022

Backgroud: Research on tooth regeneration using human-induced pluripotent stem cells (hiPSCs) is valuable for autologous dental recovery. Acquiring mesenchymal and epithelial cells as a resource for dental regeneration is necessary because mesenchyme-epithelium interactions play an essential role in dental development. However, the generation of dental mesenchyme from hiPSCs has not yet been reported. Objectives: This study attempts to establish hiPSC-derived mesenchymal stem cells (MSCs) with odontogenic potential. Since most dental MSCs are derived from the neural crest, hiPSCs were induced to differentiate into MSCs through neural crest formation to acquire the properties of dental MSCs. Methods: To differentiate into the neural crest, established human iPSCs were cultured and differentiated on PA6 stromal cells, and differentiated hiPSCs formed neurospheres on ultralow attachment plates. Neurospheres were cultured in serum-supplemented medium and differentiated into MSCs. The properties of neural crest-mediated MSCs (NC-MSCs) were verified by characterization of MSC markers and coculture with Hertwig's epithelial root sheath/epithelial cell rests of Malassez (HERS/ERM). Results: The results showed that NC-MSCs continuously expressed MSC markers for 15 passages. NC-MSCs and HERS/ERM cocultured under odontogenic induction conditions expressed odontogenic/osteogenic-related genes and DSPP proteins and yielded calcium deposits. Under in vivo conditions, NC-MSCs cocultured with HERS/ERM expressed DSPP proteins and formed dentin-like structures after 12 weeks. Conclusion: These results indicated that NC-MSCs established from hiPSCs are a novel cell source for dental recovery.
Deep Learning Approach for Classifying the Aggressive Comments on Social Media: Machine Translated Data Vs Real Life Data
Authors: akter shapna , Ahmed Nova
Published: April 2022

Aggressive comments on social media negatively impact human life. Such offensive contents are responsible for depression and suicidal-related activities. Since online social networking is increasing day by day, the hate content is also increasing. Several investigations have been done on the domain of cyberbullying, cyberaggression, hate speech, etc. The majority of the inquiry has been done in the English language. Some languages (Hindi and Bangla) still lack proper investigations due to the lack of a dataset. This paper particularly worked on the Hindi, Bangla, and English datasets to detect aggressive comments and have shown a novel way of generating machine-translated data to resolve data unavailability issues. A fully machine-translated English dataset has been analyzed with the models such as Long Short term memory model (LSTM), Bidirectional Long-short term memory model (BiLSTM), LSTM-Autoencoder, word2vec, Bidirectional Encoder Representations from Transformers (BERT), and generative pre-trained transformer (GPT-2) to make an observation on how the models perform on a machine-translated noisy dataset. We have compared the performance of using the noisy data with two more datasets, such as raw data, which does not contain any noises, and semi-noisy data, which contains a certain amount of noisy data. We have classified both the raw and semi-noisy data using the aforementioned models. To evaluate the performance of the models, we have used evaluation metrics such as F1-score, accuracy, precision, and recall. We have achieved the highest accuracy on raw data using the gpt2 model, semi-noisy data using the BERT model, and fully machine-translated data using the BERT model. Since many languages do not have proper data availability, our approach will help researchers create machine-translated datasets for several analysis purposes.
Necdin inhibits the proliferation of osteosarcoma cells by regulating the expression of VEGFA
Authors: Wu Zhuangzhuang , Chen Shiwei , Jin Wenxuan , Feng Yi , Li Pengcui , Guo Li , Bai Junjun , Qiao Xiaochen , Yang Meiju , Lv Zhi
Published: April 2022

Necdin (NDN) acts as a tumor suppressor gene in some malignant tumors, but it is unclear about the role of NDN in osteosarcoma (Osteosarcoma, OS). The results show that the expression level of NDN is low, while that of vascular endothelial growth factor A (VEGFA) is significantly up-regulated in OS cells and tissues. Overexpression of NDN can accelerate apoptosis of OS cells making them less invasiveness, and reduce the tubular shape of human umbilical vein endothelial cells. Meanwhile, the overexpression of NDN can inhibit the expression of VEGFA. Bioinformatics analysis demonstrates that there is no noticeable relationship between NDN and VEGFA and no statistical significance. The studies in vivo further confirmed that NDN could inhibit tumor growth and angiogenesis in xenograft nude mice. Our results show that NDN is a potential tumor suppressor in OS, and it can inhibit tumor angiogenesis by regulating VEGFA. Therefore, NDN may be a new biomarker for the prognosis and a new target for treatment of OS.
Amyotrophic Lateral Sclerosis and Cerebellum
Authors: Kabiljo Renata , Iacoangeli Alfredo , Al-Chalabi Ammar , Rosenzweig Ivana
Published: April 2022

Amyotrophic lateral sclerosis (ALS) is a devastating, heterogeneous neurodegenerative neuromuscular disease that leads to a fatal outcome within two to five years, and yet, a precise nature of the association between its major phenotypes and the cerebellar role in ALS pathology remains unknown. Recently, repeat expansions in several genes in which variants appreciably contribute to cerebellar pathology, including C9orf72, NIPA1, ATXN2 and ATXN1, have been found to confer a significant risk for ALS. To better define this relationship, we performed MAGMA gene-based analysis and tissue enrichment analysis using genome-wide association study (GWAS) summary statistics based on a study of 27205 people with ALS and 110881 controls. Our preliminary results imply a striking cerebellar tissue specificity and further support increasing calls for re-evaluation of the cerebellar role in the ALS pathology.
Redox-dependent Structural Origin of the Temperature Threshold and Sensitivity in the TRPV3 Thermometer
Authors: Wang Guangyu
Published: April 2022

The DNA hairpin with a limited size is sensitive to temperature. However, it is unclear if thermosensitive TRP channels also use temperature-dependent hairpin sizes to govern their activation temperature thresholds and sensitivity. Here, graph theory, together with redox- and state-dependent cryo-electron microscopy structures of TRPV3 with or without the Y564A mutation at different temperatures, was to test this hypothesis. The results showed that the largest hairpin topological loop size and a change in total hairpin sizes along the channel gating pathway control the temperature threshold and sensitivity, respectively. This size-dependent hairpin thermodynamics may mediate the thermal activity of biological macromolecules.
Amplification of integrated microscopic motions of high-density [2]rotaxanes in mechanically interlocked networks
Authors: Yang Xue , Cheng Lin , Zhang Zhaoming , Zhao Jun , Bai Ruixue , Guo Zhewen , Yu Wei , Yan Xuzhou
Published: April 2022

Integrating individual microscopic motion to perform tasks in macroscopic sale is common in living organisms. However, developing artificial materials in which molecular-level motions could be amplified to behave macroscopically is still challenging. Herein, we present a class of mechanically interlocked networks (MINs) carrying densely rotaxanated backbones as a model system to understand macroscopic mechanical properties stemmed from the integration and amplification of intramolecular motion of the embedded [2]rotaxane motifs. On the one hand, the motion of mechanical bonds introduces the original dangling chains into the network, and the synergy of numerous such microscopic motions leads to an expansion of entire network, imparting good stretchability and puncture resistance to the MINs. On the other hand, the dissociation of host−guest recognition and subsequent sliding motion represent a peculiar energy dissipation pathway, whose integration and amplification result in the bulk materials with favorable toughness and damping capacity. Thereinto, we develop a continuous stress-relaxation method to elucidate the microscopic motion of [2]rotaxane units, which contributes to the understanding of the relationship between cumulative microscopic motions and amplified macroscopic mechanical performance. The fundamental insights gained from the study of high-density mechanically bonded networks would facilitate the fabrication and application of mechanically interlocked materials.
Two novel Erwinia amylovora bacteriophages Loshitsa2 and Micant, isolated in Belarus
Authors: Besarab Natalya , Letarov Andrey V. , Kulikov Eugene E. , Babenko Vladislav V. , Belalov Ilya S. , Lagonenko Alexander L. , Golomidova Alla K. , Evtushenkov Anatoly N.
Published: April 2022

The complete genomes of new Erwinia amylovora bacteriophages, Loshitsa2 and Micant, are 43092 bp and 43028 bp, respectively, encode 51 putative proteins and have two tRNA genes. Comparative analysis with Caudovirales representatives suggests that Loshitsa2 and Micant bacteriophages are related to LIMElight bacteriophage within the family Autographiviridae, and could be proposed to share novel subfamily.
A de novo assembled high-quality chromosome-scale Trifolium pratense genome and fine-scale phylogenetic analysis
Authors: Yan Zhenfei , Sang Lijun , Ma Yue , He Yong , Sun Juan , Ma Lichao , Li Shuo , Miao Fuhong , Zhang Zixin , Wang Zengyu , Yang Guofeng
Published: April 2022

Background: Red clover (Trifolium pratense L.) is a diploid perennial temperate legume with 14 chromosomes (2n=14) native to Europe and West Asia, with high nutritional and economic value. It is a very important forage grass and is widely grown in marine climates, such as the United States and New Zealand. Genetic research and molecular breeding are limited by the lack of high-quality reference genomes. In this study, we used Illumina, PacBio HiFi, and Hi-C to obtain a high-quality chromosome-scale red clover genome and used genome annotation results to analyze evolutionary relationships among related species. Results: The red clover genome obtained by PacBio HiFi assembly sequencing was 423 M. The assembly quality was the highest among legume genome assemblies published to date. The contig N50 was 13 Mb, scaffold N50 was 55 Mb, and BUSCO completeness was 97.9%, accounting for 92.8% of the predicted genome. Genome annotation revealed 44,588 gene models with high confidence and 52.81% repetitive elements in red clover genome. Based on a comparison of genome annotation results, red clover was closely related to Trifolium medium and distantly related to Glycine max, Vigna radiata, Medicago truncatula, and Cicer arietinum among legumes. Analyses of gene family expansions and contractions and forward gene selection revealed gene families and genes related to environmental stress resistance, protein synthesis, and energy metabolism.Conclusions: We report a high-quality de novo genome assembly for the red clover at the chromosome level, with a substantial improvement in assembly quality over those of previously published red clover genomes. These annotated gene models can provide an important resource for molecular genetic breeding and legume evolution studies. Furthermore, we analyzed the evolutionary relationships among red clover and closely related species, providing a basis for evolutionary studies of clover leaf and legumes, genomics analyses of forage grass, the improvement of agronomic traits.
Strong linkage of carbon and nitrogen mineralization in rhizosphere soils along an altitudinal forest gradient of Changbai Mountain
Authors: Huo changfu , Lu Jiayu , Yin Liming , Wang Peng , Cheng Weixin
Published: April 2022

Aims
Rhizosphere is a hotspot for soil C and N biogeochemical cycling in terrestrial ecosystems. Our understanding of interaction between C and N mineralization mainly comes from the bulk soils, yet it is unknown the interaction in the rhizosphere soils. The study aimed to identify interactions between soil C and N mineralization in paired rhizosphere soils and bulk soils.
Methods
We used the “soil adhering to fine roots after shaking” method to collect paired rhizosphere soils and bulk soils along an altitudinal forest gradient. Soil C mineralization rates (Cmin) and net N mineralization rates (Nmin) were determined with laboratory incubation.
Results
We found a strong positive relationship between Cmin and Nmin in the rhizosphere soils across sites, whereas Cmin was not correlated with Nmin in the bulk soils. Furthermore, soil properties, microbial biomass C (MBC) and extracellular enzyme activities showed substantial paths affecting Cmin and Nmin using structural equation model. The coupling of Cmin and Nmin in rhizosphere soils could be triggered by root-soil interactions, resulting in the higher level of MBC, soil total C, soil total N, extracellular enzyme activities and specific microbial community structure. By contrast, the decoupling of Cmin and Nmin in the bulk soils might be attributed to the lower level of MBC and extracellular enzyme activities.
Conclusions
Our results demonstrated that soil C and N mineralization coupled in the rhizosphere rather than the bulk soils. These results highlight the need to distinguish rhizosphere from bulk soils for simulating soil C and N cycling in terrestrial ecosystems.
Evidence-based analysis of the SARS-CoV-2 furin site origin
Authors: Romeu Antonio R.
Published: April 2022

The origin of the SARS-CoV-2 is still unclear. Simply said, its emergence is due to the acquisition of the polybasic furin cleavage site on the S protein in one of its closest relatives. The recent discovery in Laos of bat Rhinolophus coronaviruses that contain receptor binding domains almost identical to that of SARS-CoV-2, and despite not having the furin site, they can therefore infect human cells (1), is the cornerstone to identify the SARS-CoV-2 progenitor. However, it is not yet known where the insertion of the furin site at the S1/S2 junction in the S protein of the pandemic virus came from. Not only from where, but also how, where and when of such acquisition. The most surprising was: (i) that the polybasic furin cleavage site is unique to SARS-CoV-2 among Sarbecovirus (2), and (ii) that the inserted four amino acid motif has a CGG-CGG encoded arginine pair which is rare in coronaviruses (3). So, my question is if the SARS-CoV-2 insert in the S gene insert would match to human transcripts. Here, I address this issue by using NCBI and GISAID databases, the NCBI Human Genome Resources, sequence analysis tools and in-house developed bioinformatic tools. I found that the 12-nucleotide insert encoding SARS-CoV-2 furin site 100% match to several human transcripts. Taken together the presence of these human transcripts and the expression patterns their genes, results provide insight into human potential recombination link to SARS-CoV-2 furin cleavage site, during undetected human-to-human virus transmission. Other PRRA-like insertions in the SARS-CoV-2 spike protein are shown.
Chemokine CCL5 immune subtypes of human liver cancer with prognostic significance
Authors: Xia Yin , Zhou Linlin , Yang Hung-Chih , Yu Chen-Wei
Published: April 2022

Background The immunogenicity of the liver tumor microenvironment is clinically heterogeneous and mysterious. The insight into the role of immune cells including tumor-infiltrating lymphocytes (TILs) and chemokine networks, might enable optimal patient selection for immunotherapy. In this study, we aimed at characterizing the liver cancer immune subtypes linked to chemokines and associating with the patient characteristics and clinical outcomes. Methods We analyzed the immune cells and chemokine signatures of human liver cancer using The Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) database profiling of 110 normal liver tissues and 369 liver tumor patients. We performed hierarchical clustering to the chemokine expression by applying immune cells status to categorize the CCL5-related chemokine in liver tumors. The separation was characterized by dividing the liver tumor patients into CCL5-high and low subtypes. Results Our results showed that the high expression of myeloid-derived suppressor cells (MDSCs) is associated with a decrease in effector T cells expressing PRF1 in liver tumor progression. The chemokines and immune cells in CCL-5-high subtype including CCR5, MDSCs and effector T cells, are significantly associated with CCL5 and a potential predictive clinical benefit. The estimated odds for CCL5-low subtype liver tumors were higher than CCL5-high subtype liver tumors particularly in the stage IV tumors (OR = 3.54; 95 % CI: 0.36, 34.92). Our data demonstrated that the CCL5-high subtype significantly improved OS (p = 0.0379, hazard ratio 0.67; 95% CI 0.43, 0.98), DFI (p = 0.0104, hazard ratio 0.63; 95% CI 0.44, 0.90), PFI (p = 0.0066, hazard ratio 0.64; 95% CI 0.46, 0.89) and working performance status when compared to the CCL5-low subtype. Conclusion Our findings provide a novel perspective of liver cancer chemokine subtypes linked to immune cells. A suitable therapy that can effectively activate effector T cells and inhibit MDSCs targeting chemokines might support the magnitude of lymphocytic infiltration in liver tumors, and should be considered for the design of precision therapies targeting the tumor and its immune microenvironment. The chemokine signatures in the CCL5-subtype are a valuable resource for future research to help identify clinically relevant biomarkers.
Dyslipidemia and its association with early mortality in children with hemophagocytic lymphohistiocytosis：a retrospective cohort study of 353 Chinese patients
Authors: Xiao Li , Xu Ximing , Zhang Zhiling , Dou Ying , Guan Xianmin , Guo Yuxia , Wen Xianhao , Shen Yali , Meng Yan , Liao Meiling , Hu Qinshi , Yu Jie
Published: April 2022

Background
Hemophagocytic lymphohistiocytosis (HLH) is a rapidly progressive and potentially life-threatening disorder. Identifying risk factors and timely adjustment of the given treatment regimens is critical to reducing the early mortality in HLH patients. Hypocholesterolemia has been reported to be associated with poor prognosis in a variety of critical illnesses. However, serum cholesterol is rarely studied in HLH patients, and its prognostic value is unclear.
Methods
We conducted a retrospective cohort study in National Clinical Research Center for Child Health and Disorders (Chongqing), identifying pediatric HLH patients diagnosed with the HLH-2004 protocol and treated with immunochemotherapy between January 2008 and December 2020. The patients’ blood lipid levels at initial diagnosis of HLH, including triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein- cholesterol (LDL-C), were reviewed based on electronic medical records. Both Cox and logistic regression models were used to estimate the effects of blood lipid indicators on early death (within 30 days after diagnosis).
Results
The observed 30-day mortality rate of the 353 included patients was 19.05% (64/336, 17 were lost to follow-up). The Kaplan-Meier-estimated 3-year survival rate was 61.67% (95% CI, 56.27%-67.59%). Lipid panel was performed in 349 patients: 91.98% (321/349) had TG ≥ 1.80 mmol/L, 92.84% (324/349) had HDL-C ≤ 1.04 mmol/L, 58.74% (205/349) had LDL-C ≤ 1.30 mmol/L and 24.64% (86/349) had TC ≤ 3.11 mmol/L. TC ≤ 3.11 mmol/L and BUN ≥ 7.14 mmol/L were the independent risk factors for 30-day mortality [HR(95%CI): 2.85(1.46, 5.57) and 2.90(1.48, 5.68), respectively]. Compared with the low-risk group (no risk factors present), the patients had a nearly 10-fold increased risk of early death [HR = 9.98, 95%CI: (4.23, 23.56)] in the high-risk group (two risk factors were present) and a 6-fold increased risk of early death [HR = 6.24, 95%CI: (3.18, 12.22)] in the intermediate-risk group (one risk factor was present).
Conclusion
Severe derangement of lipoproteins is common in children with HLH, and decreased TC is an independent risk factor for early death. More attention needs to be paid to hypocholesterolemia during the diagnosis and management of HLH patients.
Advancing small-animal perfusion models: Normothermic dual-vessel ex vivo rat liver machine perfusion based on a clinical setup
Authors: Strobl Felix , Michelotto Julian , Muth Vanessa , Moosburner Simon , Knaub Kristina , Zimmer Maximilian , Pratschke Johann , Sauer Igor Maximilian , Raschzok Nathanael , Gassner Joseph Maria George Vernon
Published: April 2022

Normothermic ex vivo liver machine perfusion (NEVLP) has been developed to address organ shortage in liver transplantation. To establish new therapeutic concepts for the expansion of the donor pool, standardized animal models are needed, that simulate clinical NEVLP. Rat liver grafts were perfused in a dual-vessel NEVLP system using varying doses of the clinically used vasodilator epoprostenol, with and without the addition of the Kupffer cell inhibitor glycine. Cell culture medium supplemented with rat plasma was compared to SteenTM-based perfusion solution, which is used in clinical NEVLP. Perfusion pressures and bile production were recorded, perfusate transaminases levels were measured and tissue was analyzed for cytokines and 8-Isoprostane. Increasing levels of epoprostenol and the addition of glycine resulted in a stepwise decrease of transaminase secretion and improved bile production. SteenTM significantly decreased transaminase secretion as well as IL-1β production, resulting in lowest levels of oxidative stress and best-preserved liver integrity. In conclusion, high doses of epoprostenol seem to ameliorate liver function and prevent cellular damage, with glycine acting synergistically. SteenTM as perfusion basis seems superior. Our rodent NEVLP system may be used to rapidly test new agents for pharmacologic conditioning of livers and to translate these findings from bench-to-bedside.
Incompatible insect technique mass rearing infrastructure cost calculator for the control of Culex quinquefasciatus in Hawaiʻi
Authors: Vorsino Adam E. , Xi Zhiyong
Published: April 2022

BackgroundHawaiʻi’s native forest avifauna is experiencing drastic declines due to climate change induced increases in temperature encroaching on their upper elevation montane rainforest refugia. Increasing temperature supports higher avian malaria infection rates due to increasing densities of its primary vector, the southern house mosquito C. quinquefasciatus, and an increase in developmental success of the avian malaria parasite Plasmodium relictum. Here we propose the use of the Incompatible Insect Technique (IIT) or the combined IIT/Sterile Insect Technique (SIT) for the landscape scale control of C. quinquefasciatus, and have developed a calculator to estimate the costs of IIT and IIT/SIT applications at various sites in Hawaiʻi.MethodsThe calculator described here links the infrastructure, personnel and space necessary to deploy a larval rearing unit (or units) that can rear ~ 1 million Culicid/week. We assessed the rearing costs and needs for effective control at various elevations in Hawaiʻi using approximations of the overflooding ratio at each elevation. The calculator derives a rate describing the number of Culicid needed to control wild-type mosquitoes at each site/elevation, in relation to the number of larval rearing units. This rate is a constant from which other costs are quantified. With minor modifications, the calculator described here can be applied to other areas, mosquito species, and techniques.ResultsAs a proof of concept, we have used the calculator to estimate rearing infrastructure costs for an application of IIT in the Alakaʻi Wilderness Reserve on the island of Kauaʻi. Our analysis estimates an initial investment of at least $1,338,874.00 with subsequent yearly costs of approximately $751,764.00. We also present supplemental examples of infrastructure costs needed to control C. quinquefasciatus in the home range of ʻiʻiwi Drepanis coccinea, and the yellow fever vector Aedes aegypti.ConclusionsThe linear relationship of rearing infrastructure to cost used in this calculator is a simplified metric that can be useful for the development of initial Culicid mass rearing infrastructure cost estimates. Users of the calculator can modify the inputs to reflect project specific parameters.
The value of myocardial work in assessment of ventricular function in patients with hypertrophic cardiomyopathy
Authors: Yang Chenguang , Guo Ying , Wang Xiang , Zhang Ruisheng , Wang Fang , Zhu Huolan
Published: April 2022

Background: To evaluate myocardial work using speckle tracking echocardiography in patients with hypertrophic cardiomyopathy (HCM). Methods: Fifty patients with HCM and 50 normal controls were included. Left ventricular ejection fraction (LVEF) was quantified using the bi-plane Simpson’s method. Myocardial work parameters, which included global work index (GWI), global constructive work (GCW), global waste work (GWW), and global work efficiency (GWE), were derived from the 2D strain-pressure loop. Results: The patient group was older (49.19 ± 14.69 versus 37.16 ± 7.49 years old) and had a higher body mass index (24.93 ± 3.67 versus 23.26 ± 3.32 kg/m2) and systolic blood pressure (121.81 ± 16.50 versus 115.30 ± 11.01 mmHg) (P < 0.05). The mean LVEF in patients was 51%, with 54% of patients had LVEF ≤ 50%. Compared to controls, GWI (946.42 ± 360.64 versus 1639.72 ± 204.56 mmHg%), GCW (1176.94 ± 373.23 versus 1960.16 ± 255.72 mmHg%), and GWE (83.96 ± 7.68 versus 95.26 ± 1.98%) were significantly decreased, while GWW (158.17 ± 82.47 versus 79.12 ± 40.26 mmHg%) was significantly increased (P < 0.05) in the patient group. In patients, GWE showed a trend of positive correlation with LVEF (r = 0.276, P = 0.06), while GWW had a trend of negative correlation with LVEF (r = -0.241, P = 0.09). There was no correlation between LVEF and GWI or GCW. Conclusions: Assessing myocardial work adds useful information of LV function in patients with HCM.
Estimated global cost of treating COVID-19, HIV, Hepatitis B and Hepatitis C with approved effective oral medications
Authors: Ellis Leah , Wang Junzheng , Pilkington Victoria , Levi Jacob , Heath Katherine , Hill Andrew
Published: April 2022

Background
High drug prices can limit treatment access. Patented drugs can be sold for prices far higher than the costs of production. This analysis aimed to determine prices currently feasible to treat COVID-19, HIV, and Hepatitis B or C, with WHO/FDA/NICE approved oral medications assuming competitive generic manufacture.
Methods
Data on Active Pharmaceutical Ingredients (API) exported from India were collected from the Panjiva database ( www.panjiva.com ) – an online database of global exports – and were used to calculate current weighted mean cost/kg of API. Target prices were calculated based on the per-pill cost of API, plus costs of manufacture ($0.01/pill), 10% profit margin, and assumed 27% tax on profit. We selected a range of the most commonly used oral treatments based on WHO guidelines for treatment of COVID-19, HIV, HBV and HCV. Current lowest global prices were obtained from public reports and the Pan American Health Organization Antiretroviral Report. Our target prices were compared with national pricing data from a range of low, middle, and high-income countries.
Results
The main results table shows current prices of antiretrovirals for SARS-CoV-2 (5–14-day course), HIV or HBV (per 365-day course), and HCV treatments (per 12-week course). COVID-19 can be treated with molnupiravir for $12.40, baricitinib for $0.60, or dexamethasone for $0.19 per course. HIV can be treated with DRV/r for $286 per year, ATV/r for $140 per year, TDF/3TC/DTG for $74 per year, TAF/FTC/DTG for $89 and TDF/FTC for $59. HBV can be treated with TDF for $23 per year and TAF for $38 per year. HCV could be cured with sofosbuvir/daclatasvir for $35 per patient and sofosbuvir/velpatasvir for $79 per patient. Maximum list prices (typically from US) were up to 600 times higher than costs of production (e.g. for TDF).
Conclusions
Key viral infections can be treated or cured with generic drugs at prices far below those of branded equivalents. Use of branded drugs at high prices can limit the potential for countries to achieve the UNAIDS 95-95-95 targets.
PERCEPTION OF RIBA ACCORDING TO MTR-MASYARAKAT TANPA RIBA (A COMMUNITY WITHOUT USURY)
Authors: Wigati Sri
Published: April 2022

ABSTRAK

Lahirnya komunitas Masyarakat Tanpa Riba (MTR) ini dilatarbelakangi adanya dua alasan utama yaitu: pertama, keprihatinan atas Indonesia, negeri yang penduduknya mayoritas muslim namun secara sistemik dan massif melegalkan riba melalui adanya bank konvensional. Kedua, gerakan ini dilatarbelakangi dengan adanya kesadaran atas dasar konsep pemikiran cemerlang (akidah Islam) untuk membangkitkan umat muslim Indonesia dari keterpurukan multidimensi, khususnya jebakan dan jeratan ribawi.

Penelitianinimerupakanpenelitiankualitatif dan menggunakanpenelitianlapangan (field research).Pendekatan yang digunakanadalahfenomenologi.Dalampengamatanmelihatperubahancaraberfikirmasyarakatdalamkehidupan. Teknikpengumpulan data denganobservasipastisipatif, wawancara dan dokumentasi. Hasil penelitian menunjukkan bahwa: .Tidak ada konsistensi terhadap sejarah munculnya MTR meskipun tidak sepakat terhadap bank, baik bank syariah maupun bank konvensional. Akan tetapi MTR juga tidak menunjukkan lembaga keuangan yang menurut MTR anti riba dan tetap memakai bank di Indonesia sebagai alat untuk sarana kegiatan MTR seperti bentuk transfer peserta dll.
PERFORMANCE ANALYSIS OF WAQF INSTITUTION USING BALANCED SCORECARD ANALYSIS: CASE STUDY AT LAZNAS YATIM MANDIRI
Authors: Febriandika Nur Rizqi
Published: April 2022

This research aims to measure the performance of the waqf institution (LAZNAS Yatim Mandiri) using a balanced scorecard (BSC). This study uses quantitative and qualitative analysis or mixed-method by using a balanced scorecard (BSC). The Balanced Scorecard is used to measure performance from both a financial perspective and a non-financial perspective, which includes four main perspectives: (1) finance, (2) customers, (3) internal business processes, and (4) learning and growth. The study found that an overall BSC score of 85,6% shows that the performance of LAZNAS Yatim Mandiri is categorized as very good. From each perspective, customer perspective is the highest BSC score, followed by financial perspective and internal business while learning and growth perspective gain the lowest score. The BSC suggests a direction of priority to improve each strategic goal of perspective. Customer satisfaction becomes the first place, followed by waqf collection and distribution as the second priority. The next priority is employee satisfaction while keeping other strategic goals to be maintained. The findings of this study could help Islamic philanthropic institutions define their vision and strategy, as well as change their vision and strategy into specific activities, by implementing measures that are accurate and comprehensive, as well as providing information that is accurate and correct for managers to make business decisions.
BERKAH DALAM PERILAKU KONSUMSI MASYARAKAT MUSLIM PERUMAHAN TULUNGAGUNG
Authors: Nurohman Dede
Published: April 2022

This study aims to reveal the interpretation of the Muslim housing community about the meaning of blessings in their lives and relate it to their consumption behavior, especially in determining the criteria for sellers that contain blessings. This study used a qualitative approach and data mining was carried out using interview, observation and FGD techniques. This study found that their interpretation of blessings was divided into three, namely; blessing as a transcendent value, blessing as a condition, and blessing as a means. In the context of consumption activities, their understanding of the seller's criteria states that the seller's blessing lies with three criteria, namely; sellers who are elderly and serve honestly and friendly, sellers who have the status of students, have the title hajj/hajah, and sellers are male. This finding is expected to provide consideration for the importance of the blessing factor in the formulation of the theory of consumption behavior in Islam.
Nilai-nilai Murni Dalam Cerita Legenda di Lembangan Sungai Pengkalan Datu, Kelantan
Authors:   Faculty of Creative Technology and Heritage, Universiti Malaysia Kelantan, Kelantan, Malaysia, Che Yaacob Mohd Firdaus
Published: April 2022

Legendary stories are historical tales about figures and places among the local community in the past. This study was conducted because the average society today is not aware of the existence of legendary stories which are rich in values and become a symbol of historical splendour among the community in Kelantan. Society also considers legendary stories as mere entertainment, untrue, imaginary and fantasy. This study aims to identify and analyse the values in legendary stories in the Lembangan Sungai Pengkalan Datu, Kelantan. This study is qualitative in nature, involving library methods, interviews and study analysis. In addition, the spiritual concepts approach contained in the National Education Philosophy is used as a deductive study to ensure a more robust analysis of the study. The findings of this study can be proven through the discovery of legendary stories that are rich in positive values such as kind-heartedness, humility, respect and love among humankind, all of which can be used as a guide for life among the local community. Thus, these positive values can be internalised as practices and lessons to form a civilised society.