bluuebunny/crossref_metadata_2025 huggingface dataset:
KEPEMIMPINAN DAN OPTIMALISASI FUNGSI LEMBAGA PENDIDIKAN ISLAM NON FORMAL
Authors: Mubarok Ramdanil
Published: May 2023

Penelitian ini dilakukan untuk menggambarkan kepemimpinan di lembaga pendidikan Islam non formal, dan menganalisa optimalisasi fungsi lembaga pendidikan Islam non formal. Artikel ini diharapkan biasa memberikan saran dan masukan yang positif bagi pemimpin lembaga pendidikan non formal untuk mengoptimalkan fungsi lembaga yang dipimpinnya. Metode penelitiannya adalah menggunakan metode penelitian kualitatif. Salah satu jenis dalam penelitian kualitatif adalah penelitian kepustakaan (Library research). Peneliti mengumpulkan data-data penelitian dengan membaca buku, makalah, artikel jurnal, dan penelitian-penelitian yang relevan dan menguraikan dan mengkaji secara kritis serta menyatukan ide-ide yang berkaitan dengan kepemimpinan dan optimalisasi fungsi lembaga pendidikan non formal. Hasilnya adalah kepemimpinan di lembaga pendidikan Islam non formal harus mampu membangun relasi, menjalankan roda organisasi, mempengaruhi orang lain, mengarahkan dan mengkoordinasikan, melakukan pengawasan, melaksanakan proses dan tindakan yang berorientasi pada tercapainya tujuan yang telah direncanakan. Sedangkan optimalisasi fungsi lembaga pendidikan Islam Non formal dapat dilakukan dengan mengembangkat bakat, melestarikan budaya sekitarnya, dan membina keterampilan. Optimalisasi fungsi lembaga pendidikan islam non formal yaitu dengan berbakti kepada orang tua, dan mempertahankan sistem sosial masyarakat.
Opportunities and Challenges of Using FinTech in Takaful Financial Services
Authors: Faqih Rijalul , Nurhayati Nurhayati
Published: May 2023

Fintech is currently part of the development of takaful, the results of research and studies related to this problem are still very limited, on the other hand all financial services industries are starting to shift to fintech, including the Islamic financial services industry. So it is necessary to explore the potential use of fintech in the sharia insurance industry, especially in terms of opportunities and challenges in the future. In particular, big data analytics and robo-advisory are explored and how  takaful  operators can combine  them for better customer experience  and gathering  competitive intelligence.  To  stay  competitive in  a  rapidly changing business environment, takaful operators need to identify and adopt fintechs that can positively impact customer experience and optimize cost efficiency.
ANALISIS PENGELOLAAN WAKAF PRODUKTIF DALAM EFEKTIVITAS PEMBERDAYAAN SOSIAL EKONOMI MASYARAKAT KOTA MEDAN
Authors: Kausar Al , Soemitra Andri , Batubara Chuzaimah
Published: May 2023

The purpose of this study was to examine and find out the management of waqf in an effort to effectively empower the socio-economic community of the city of Medan. The type of research used is field research (field research) with a qualitative descriptive approach which describes data and information based on data obtained in the field. In this case the author conducted a case study on 3 foundations, namely the H. Anif Foundation, the Al-Jihad Mosque Foundation , and the Ar-Raudatul Hasanah Foundation. The results of the research showed that the implementation of productive waqf management in Medan was a case study of 3 foundations, only 2 foundations had productive waqf and 1 still emphasized infaq and alms. 2 foundations that have productive endowments emphasize social and economic aspects.
Unleashing the Power of Family Education in the Post-Covid-19 Era: Quranic and Hadith Perspective
Authors: Salam Mukhtar Muhammad , Hasan Muhammad
Published: May 2023

The aim of this study is to analyze education in the post-COVID-19 era from the perspective of the Quran and Hadith. In the post-pandemic era, the strength of the family is crucial in facing various challenges. In this context, family education plays a vital role in shaping a strong and resilient family. With the perspective of the Quran and Hadith, family education can be optimized to produce a more robust, resilient, and positively contributing family in society. Family education can cover various aspects, including character education, religious education, and social skills, all of which can be linked to the perspective of the Quran and Hadith. By utilizing the perspective of the Quran and Hadith, families can become centers of learning, support each other, and have a strong sense of responsibility in building a better society. Therefore, the revitalization of family education in the post-COVID-19 era is essential to create stronger and more resilient families in facing an uncertain future. The method used is a literature review and content analysis of verses from the Quran and Hadith related to family and education. The data collected were analyzed using a qualitative approach and interpreted according to the current context. The results of this study show that the Quran and Hadith provide clear and practical guidance for forming strong and resilient families in the post-COVID-19 era. The perspective of the Quran and Hadith can help families build confidence, a spirit of mutual respect, and strengthen the sense of responsibility and unity within the family. Moreover, family education based on the perspective of the Quran and Hadith can also help families face various challenges and complex situations in the post-COVID-19 era.
Creativity in Philosophy: A Multifaceted Approach to Education with Mulla Sadra's Thinking
Authors: Hosseini Afzal Sadat
Published: May 2023

Solving today's problems and preparing for future uncertainties requires creativity. Creativity has been placed as one of the main axes of educational reforms in many advanced educational systems of the world. The current research, which is of a fundamental type and descriptive-analytical method, seeks to explain the solid philosophical foundations for the multifaceted theory of educational creativity presented by the author of this article based on Mulla Sadra. Mulla Sadra is one of the great Muslim philosophers. According to the findings of the present research, the theory of multifaceted educational creativity, which has environmental-social, emotional-cognitive, intellectual, educational-teaching and physical dimensions for creativity, can be based on the anthropological philosophy of Mulla Sadra, which attributes "becoming" to human nature. In this article, several practical suggestions for teachers based on the theory of multifaceted educational creativity have been presented so that teachers can take more effective steps to foster students' creativity. Also, suggestions for future researches have been provided.
The Effects of Extracted Peptide from Skin of Iraqi Frog (Rana ridibunda) on Human Leukemic Lymphocytes
Authors: Al-Khafaji Ali Jabbar Oleiwi
Published: May 2023

The purified frog skin peptides were tested on leukemic patients lymphocytes, which revealed effects of cytotoxicity. Four frogs (Rana ridibunda) were stimulated by single intra-peritoneal injection of norepinephrine-HCl . Five different peptides;1(18) A, 2(19) L, 3(20) I,4(21) E and 5(22) Y were isolated and quantified. The peptide 3(20)I had 5.87% of hemolysis, while healthy human lymphocytes cytotoxic activity was for 2(19)L with inhibition( -10.4%).All peptides were subjected to polyacrylamide gel electrophoresis. The results revealed peptides 1(18)A, 2(19)L, 3(20)I which appeared as low as 10 KDa  marker. Theoretically, the whole polypeptide had a molecular weight 7488.61 Dalton and contained on 62.405 amino acid (a.a). The peptide 4(21)E had a highest inhibitory effect(46%) on tumor cell line L20B. Furthermore , peptides effects on acute  and  chronic  myeloid  lymphocytic  leukemia  patients cell cultures  revealed  peptides selectivity  in  their  action according  to  their net charge  and functional  group as  reactant  proton  donor by the  evidence  of peptide 5(22)Y, 16.22 Dalton  so  it  was  either N—terminus (--NH2) or  C—terminus (--OH)  that  led  to  cross  cell  membrane then acted as antigen mediated and activated  cells in a high significant  value (-142.37± 47.69)for acute myeloid  lymphocytic leukemia .Both  of peptides  3(20) I  and  2(19) L were revealed  a  highly significant  differences  within  Chr.40  and Chr. 22 of  inhibition  effects  by testing  volumes 15 µl and 10 µl . Those inhibition  effects  were due to  peptides  reaction  with  mitochondrial  membrane  which  led  to apoptosis . Conclusion; Frog skin peptides have a therapeutically worth for malignant diseases. Also some of peptides were activated lymphocytes may to cure immunodeficiency.
Hydrochemistry of Groundwater in Northeast Part of Anbar Governorate – West of Iraq
Authors: Al-Sudani Hussein Ilaibi Zamil
Published: May 2023

A groundwater quality assessment has been carried out in northeast part of Anbar governorate in western Iraq. We analyzed hydrochemical parameters such as pH, electrical conductivity, total dissolved solids presence of ions to describe groundwater quality. The study area has the only confined aquifer within the geological formation extended in area. Values of groundwater hydrochemical parameters were ranged from (7) to (7.9) for ph, (1599) to (6800) µmhos/cm for electrical conductivity (EC) and (1048) to (4446) mg/l for total dissolved solids (TDS). The origins and types of groundwater in the area were of marine origin and MgCl2 water type while only (6) samples were of continental origin and Na2SO4 water type. Groundwater utilization indicated that it can't be used for drinking purposes, while few groundwater wells can be used for agricultural and (33) groundwater samples can be used for animal purposes. However, the nature of the soil in the area and the depth of the groundwater qualified water for agricultural uses in significant and wide ranges.
A Preliminary Study for Solving the Gap Problems in Protein Sequence Alignment
Authors: El-Lakkani Ali , El-Sherif Seham
Published: May 2023

Protein sequence alignment has many applications in molecular biology. The existing algorithms produce imperfect alignments, because of two factors: 1) the proposed gap penalty function and its parameter values 2) the gap problems. The present work is an attempt to obtain correct alignments using a novel alignment method based on the harmonic identical words present in the sequences to be aligned. To prove the accuracy of this approach, our method is applied to three pairs of sequences. The results are compared with the corresponding results obtained from three alignment programs; the EMBL-EBI EMBOSS Needle program with minimum number of gaps, the MSAEMBL-EBI MUSCLE and Clustal Omega programs. The comparison shows that, in case of highly similar protein sequences the identity and the maximum score value of our alignment method is higher than that of the EMBL-EBI EMBOSS Needle, MUSCLE and Clustal Omega programs. In case of distantly related sequences, the maximum score value of our alignment is much higher than that of the EMBL-EBI EMBOSS Needle, MUSCLE and Clustal Omega programs and the obtained percent identity is shifted from the twilight zone to the safe zone.Our results also show that the gap lengths distribution follows a power law, and this is not achieved by many current alignment programs.
Fire-resistant bio-based polyurethane foams designed with two by-products derived from sugarcane fermentation process
Authors: Capêto Ana Paula , Amorim Manuela , Sousa Sérgio , Costa Joana R. , Uribe Braian , Guimarães Ana Sofia , Pintado Manuela , Oliveira Ana L. S.
Published: May 2023

There is a great interest in replacing conventional fossil-based polymers and composites with inorganic or organic waste-based materials and filler-type additives, to promote environmental sustainability and circularity. The main objective of this study was the design of water-blown polyurethane rigid foams integrating two by-products derived from the Amyris fermentation process of production of β-farnesene. The distillation residue (FDR) was used as main polyol component in the neat formulation of the foams (PF) that it was supplemented (PFA) with 4.5% of sugarcane bagasse ash (SCBA) added as a filler with fire-retardant properties. The impact of both by-products on the foam density and morphology, and in the thermal, mechanical, and flame-retardant properties was assessed. SCBA presence led to a reduction in apparent density, cells size, and glass transition, delaying the thermal decomposition. The differences observed in the thermal conductivity and flammability test parameters suggest a visible impact of the ash incorporation, thus meeting the fire protection standard UL 94, class HB.
Highlighting the need for further optimization, this work presents a practical example of the integration of different wastes derived from the same fermentation process in the formulation of sustainable PUR foams with reduced flammability.
Characterization of UV sex chromosomes and synteny-guided phylogenomic resolution of subgenomes in Bryopsida mosses
Authors: Gao Bei , Li Xiaoshuang , Liang Yuqing , Zhang Jianhua , Oliver Melvin , Zhang Daoyuan
Published: May 2023

The UV chromosomal sex-determination system primarily found in bryophytes, together with the XY and ZW chromosomal sex-determination systems, constitute the three principal types of chromosomal sex determination systems in nature. In this report, the genome of the moss Bryum argenteum was sequenced and assembled into 11 chromosomes containing 17,721 protein coding genes. A giant female U sex chromosome demonstrated conspicuously lower gene density, higher repeat coverage, and higher GC content compared to the ten autosomes. By further characterizing the sex-chromosomes and sex-linked genes in seven chromosomal-scale Bryopsida genomes, lower gene densities and distinct GC contents were revealed to be common in all moss sex chromosomes, likely resulting from degeneration. Weaker purifying selection, as evidenced by lower codon usage preference in sex-linked genes, was shared in most but not all Bryopsida mosses. Retained genomic syntenies between U/V sex chromosomes and ancestral Bryopsida chromosome 4 provided new evidence to support an autosomal origin for sex chromosomes. The seven ancestral Bryopsida chromosomes were reconstructed to decipher and depict chromosomal evolution; Dicranidae and Bryidae mosses demonstrated one and three chromosomal fusions and evolved 13 and 11 ancestral chromosomes, respectively. Ancient whole genome duplications characterized many plant lineages including the psi polyploidy event that occurred in the early diversification of Bryopsida. By aligning the modern chromosomes to the seven reconstructed ancestral chromosomes, genomic synteny-guided phylogenomic analyses provided strong evidence for the ancestral psi event shared by Dicranidae, Bryidae and P. patens. Furthermore, ancestral chromosomal projections and a phylogenomic resolution of Bryopsida subgenomes revealed distinct and lineage-specific chromosomal loss patterns in Dicranidae and Bryidae following the psi event. Our reconstructions reinforced the evolutionary significance and phylogenetic timing of the psi event and provided systemic insights into the sex and chromosomal evolution in mosses.
Atypical Presentation of a Right Atrial Myxoma: A Case Report
Authors: Molina Guarina , Contreras Rafael , Alvarez Melissa , Goodman Jason , Yekta Arshad
Published: May 2023

BACKGROUND
Primary cardiac tumors are rare, with a reported incidence of approximately 0.02% and atrial myxomas account for approximately 15-20% of the cases. Most of these are located in the left atrium and unusually involve the right side of the heart.
CASE PRESENTATION
We present a case of a 52-year-old man who presented with chest pain, initially presumed to be acute coronary syndrome, and found to have a right atrial tumor of 6.3 cm, with a hospital course complicated by neurologic symptoms. Definite treatment included surgical removal. Pathology analysis of the mass confirmed the histology of myxoma.
CONCLUSIONS
Differential diagnoses for atrial myxomas include thrombus and other tumors such as rhabdomyomas. Clinical manifestations include fatigue, peripheral edema, ascites, and diastolic murmur similar to tricuspid stenosis. More than half of these tumors rise in the left atrium and may be complicated by neurologic symptoms secondary to embolization. Right atrial myxomas are rare and described in the literature with a myriad of symptoms, while in some cases, asymptomatic. Given the low incidence and variety in clinical picture, careful documentation of these cases is suggested for early prevention and guideline of management.
Design and Modelling the Compressive Strength of High-Performance Concrete with Silica Fume: A Soft Computing Approach
Authors: Adebanjo Abiola , Shafiq Nasir , Razak Siti Nooriza Abd , Kumar Vicky , Ahmad Farhan Syed , Singh Priyanka , Abubakar Adamu Sanni
Published: May 2023

Soft computing methods were used in this research to design and model the compressive strength of high-performance concrete (HPC) with silica fume. Box-Behnken design-based response surface methodology (RSM) was used to develop 29 HPC mixes with a target compressive strength of 80 ± 10 MPa. Cement (450–500 kg/m3), aggregates (1500–1700 kg/m3), silica fume (SF) (20–45% weight of cement) and water-binder (w/b) ratio of (0.24–0.32) were provided as input factors while the compressive strength at 7 and 28 days were analysed as responses. Datasets for the artificial neural network (ANN) prediction were generated from 87 experimental observations from the compressive strength test. Performance indicators such as p-value, coefficient of determination (R2), and mean square error (MSE) were used to assess the models. Results demonstrated that RSM worked relatively well in projecting compressive strength with model p-values < 0.05 and R2 values of 0.913 and 0.892 for compressive strength at 7 and 28 days, respectively. In addition, RSM performed better in detecting the synergistic effects of the variables on the responses. On the other hand, ANN best generalised the relationship between independent and dependent variables considering the low MSE of 12.32 and 14.60, and high R2 values of 0.912 and 0.946 for compressive strength at 7 and 28 days, respectively. Model equations were developed to predict the compressive strength of silica-based HPC after 7 and 28 days. It is considered that adopting components from both approaches could help the design process for developing consistent mixes of HPC with supplementary cementitious materials (SCMs).
An Effective Straightforward Protocol for the Treatment of Graves’ Hyperthyroidism for Primary Care Providers
Authors: Eugenio Felisha , Raza Syed M. Kazim , Hasan Ishmum , Moldovan Christina , Zopey Mohan , Davidson Mayer B. , Friedman Theodore
Published: May 2023

Background – The prevalence of hyperthyroidism is very common in the United States (approximately 1.2%) with Graves’ Disease (GD) being the most common non-iatrogenic cause. The limited number of endocrinologists and their concentration in larger cities means that primary care providers (PCPs) must treat a large number of these patients. This paper provides an effective, straightforward protocol for them to do so.Material & Methods – Patients with GD hyperthyroidism were referred to a county endocrinology clinic by PCPs in clinics that cared for medically underserved, mostly minority patients, a challenging population to treat. Hyperthyroidism was diagnosed by elevated free T4 and/or free T4 concentrations, euthyroidism by normal concentrations of both and hypothyroidism by low free T4 or elevated TSH concentrations. Patients were treated with methimazole with initial doses and up-titration based on free T4 and free T3 concentrations and down-titration by free T4 and TSH concentrations.Results – At the initial visit, 155 patients were, and 54 patients were not, respectively, taking an anti-thyroid drug. At the initial visit, patients either remained on methimazole, were started on the drug or were switched to it from propylthiouracil. The 209 patients were followed for up to 18 months. The protocol rapidly reversed the hyperthyroidism in most patients and at the end of the study, 72% were euthyroid, 19% were hyperthyroid and 9% were hypothyroid. Medication non-adherence probably accounted for those who were hyperthyroid at that time.Conclusion – PCPs following this protocol will enable them to effectively treat patients with GD hyperthyroidism.
The effect of work-family conflict on fertility intentions: evidence from China
Authors: Shi XiaoJuan , Mo FuRong
Published: May 2023

We constructed two indicators to measure work-family conflict, work-home conflict and work-family responsibility. Data from the 2019 China Integrated Social Conditions Survey Project are also used to causally estimate the effect of work-family conflict on fertility intentions. Our findings suggest that work-home conflict promotes population fertility intentions, while work-family responsibility conflict has a dampening effect on fertility intentions. The effect of work-family conflict on fertility intentions was heterogeneous in terms of gender, household registration, and educational attainment. Based on the study findings, we believe that the Chinese government should promote the population's willingness to have children in three ways: encouraging couples to share household chores, sharing family responsibilities, and shortening the number of years of education.
Elevated Serum Uric Acid in norovirus-associated Benign Convulsions with Mild Gastroenteritis in Children
Authors: Jiang Daoju , Shi Kaili , Li Suyun , Liu Guangming , Liu Zheng , Shen Jun , Li Peiqing
Published: May 2023

Background Recent studies have shown that serum uric acid levels are associated with gastroenteritis-associated benign seizures (CWG), but the diagnosis of CWG is an exclusive diagnosis. This study explored the clinical characteristics of norovirus-associated CWG to provide evidence for reducing unnecessary tests.Methods Medical records of children admitted to the Department of Emergency of Guangzhou Women and Children′s Medical Center with Stool etiology was positive for norovirus between January 2019 and January 2020 were divided into CWG group and simple gastroenteritis group ,and were reviewed and analyzed.Results A total of 89 norovirus cases were enrolled. Age of onset, male/female ratio of CWG group and simple gastroenteritis group were 49 cases, mean 20.84 ± 5.83 months and 27:22, 40 cases, mean 19.00 ± 13.48 months and, 26:14, respectively.Serum uric acid levels in CwG and simple gastroenteritis groups increased in 43 (87.8%) and 9 (22.5%) cases, respectively. The average serum uric acid level in the CwG group was significantly higher than that in the simple gastroenteritis group (564.36 ± 125.28umol/L vs 338.42 ± 141.03umol/L [mean ± standard deviation], p < 0.0001) .The potential of hydrogen(PH), bicarbonate༈HCO3–), BE bases excess༈BE༉ of CWG group were also lower than those of simple gastroenteritis group, the differences were statistically significant.Conclusion Norovirus-associated CWG should be considered in children with norovirus-associated gastroenteritis and recurrent seizures, significantly increased serum uric acid and acidosis. Lumbar puncture and cranial imaging may not be recommended.
Deciphering the Immune Landscape of Head and Neck Squamous Cell Carcinoma: A Single-Cell Transcriptomic Analysis of Regulatory T Cell Responses to PD-1 Blockade Therapy
Authors: Feriz Adib Miraki , Bahraini Fatemeh , Khosrojerdi Arezou , Azarkar Setareh , Sajjadi Seyed Mehdi , Lotfollahi Mohammad , HosseiniGol Edris , Honardoost Mohammad Amin , Saghafi Samira , Silvestris Nicola , Leone Patrizia , Safarpour Hossein , Racanelli Vito
Published: May 2023

Immunotherapy is changing the Head and Neck Squamous Cell Carcinoma (HNSCC) landscape and improving outcomes for patients with recurrent or metastatic HNSCC. A deeper understanding of the tumor microenvironment (TME) is required in light of the limitations of patients' responses to immunotherapy. Here, we aimed to examine how Nivolumab affects infiltrating Tregs in the HNSCC TME. We used single-cell RNA sequencing data from eight tissues isolated from four HNSCC donors before and after Nivolumab treatment. Interestingly, the study found that Treg counts and suppressive activity increased following Nivolumab therapy. We also discovered that changes in the CD44-SSP1 axis, NKG2C/D-HLA-E axis, and KRAS signaling may have contributed to the increase in Treg numbers. Furthermore, our study suggests that decreasing the activity of the KRAS and Notch signaling pathways, and increasing FOXP3, CTLA-4, LAG-3, and GZMA expression, may be mechanisms that enhance the killing and suppressive capacity of Tregs. Additionally, the result of pseudo-temporal analysis of the HNSCC TME indicated that after Nivolumab therapy, the expression of certain inhibitory immune checkpoints including TIGIT, ENTPD1, and CD276 and LY9, were decreased in Tregs, while LAG-3 showed an increased expression level. The study also found that Tregs had a dense communication network with cluster two, and that certain ligand-receptor pairs, including SPP1/CD44, HLA-E/KLRC2, HLA-E/KLRK1, ANXA1/FPR3, and CXCL9/FCGR2A, had notable changes after the therapy. These changes in gene expression and cell interactions may have implications for the role of Tregs in the TME and in response to Nivolumab therapy.
Efficient dispersion of organic fluorophores by size matching with a new di-functionalized spacer interleaved into layered double hydoxide
Authors: ZERBIB Guillaume , BOYER Damien , CHADEYRON Geneviève , REVERET François , LEROUX Fabrice
Published: May 2023

Strongly luminescent when diluted in aqueous solution, Sulforhodamine B (SRB) is an organic fluorescent molecule suffering from aggregation caused quenching (ACQ) in its solid state. Its co-intercalation in very small quantities (0.12 mol%) in a layered double hydroxide (LDH) matrix with phenylenedipropionate (PPA) anions, a di-functionalized new spacer matching its size, is found to be highly effective, with more than 99% of the SRB molecules uptaken. The resulting hybrid material enables luminescence with an absolute quantum yield (PLQYabs) reaching 39% under UV excitation and even reaching 60% at its maximum. The dispersion of the luminescent hybrid powder constituted of SRB molecules intercalated into LDH platelets in silicone results in homogeneous composite films with loading as high as 40 wt.% useable as masterbatch. The optical properties are found to remain after thermal treatment up to 120°C with a decrease in PLQYabs of 5% only, making it a good candidate for the development of rare-earth-free phosphors.
The thioredoxin system determines CHK1 inhibitor sensitivity via redox-mediated regulation of ribonucleotide reductase activity
Authors: Zhang Junran , Prasad Chandra , Oo Adrian , Qiu Zhaojun , Li Na , Singh Deepika , Xin Xiwen , Cho Young-Jae , Li Zaibo , Zhang Xiaoli , Yan Chunhong , Zheng Qingfei , Shao Jimin , Wang Qi-En , Kim Baek
Published: May 2023

Checkpoint kinase 1 (CHK1) is critical for cell survival under replication stress (RS). CHK1 inhibitors (CHK1i’s) in combination with chemotherapy have shown promising results in preclinical studies but minimal efficacy with substantial toxicity in clinical trials. To explore novel combinational strategies that can overcome these limitations, we performed an unbiased high-throughput screen in a non-small cell lung cancer (NSCLC) cell line and identified thioredoxin1 (Trx1), a major component of the mammalian antioxidant-system, as a novel determinant of CHK1i sensitivity. We established a role for redox recycling of RRM1, the larger subunit of ribonucleotide reductase (RNR), and a depletion of the deoxynucleotide pool in this Trx1-mediated CHK1i sensitivity. Further, the TrxR1 inhibitor auronafin, an anti-rheumatoid arthritis drug, shows a synergistic interaction with CHK1i via interruption of the deoxynucleotide pool. Together, these findings identify a new pharmacological combination to treat NSCLC that relies on a redox regulatory link between the Trx system and mammalian RNR activity.
Circulation of highly pathogenic avian influenza virus H5N1 clade 2.3.4.4b in highly diverse wild bird species from Peru
Authors: Castro-Sanguinetti Gina , Gonzalez-Veliz Rosa , Callupe-Leyva Alonso , Apaza-Chiara Ana , Jara Javier , Silva Walter , Icochea Eliana , More-Bayona Juan
Published: May 2023

Highly pathogenic avian Influenza virus (HPAIV) has emerged in unprecedented records in recent years. Despite the large reports of cases in Asia, Europe, and North America, little is known about its circulation in South America. Here, we describe the isolation, and whole genome characterization of HPAIV obtained from sampling 26 wild bird species in Peru, representing one of the largest studies in our region. Out of 147 samples analyzed, 20 were positive for detection of avian influenza virus using a qRT-PCR-based assay. Following inoculation into embryonated chicken eggs, fourteen viral isolates were obtained from which six isolates were selected for genome characterization, based on their host relevance. Our results identified the presence of HPAIV H5N1 subtype. Phylogenetic analysis revealed that these isolates correspond to the clade 2.3.4.4b, sharing a common ancestor with North American isolates and forming a novel subclade along with isolates from Chile. Altogether, changes at the amino acid levels compared to their closest relatives indicates the virus is evolving locally, highlighting the need for constant genomic surveillance. This data evidence the chances for spillover events increases as the virus spreads into large populations of immunologically naïve avian species and adding conditions for cross species transmission.
LSTM-Based Recurrent Neural Network Provides Effective Short Term Flu Forecasting
Authors: Amendolara Alfred B , Sant David , Rotstein Horacio G. , Fortune Eric
Published: May 2023

Background Influenza virus is responsible for a yearly epidemic in much of the world. To better predict short-term, seasonal variations in flu infection rates and possible mechanisms of yearly infection variation, we trained a Long Short-Term Memory (LSTM)-based deep neural network on historical Influenza-Like-Illness (ILI), climate, and population data.
Methods Data were collected from the Centers for Disease Control and Prevention (CDC), the National Center for Environmental Information (NCEI), and the United States Census Bureau. The model was initially build in Python using the Keras API and tuned manually. We explored the roles of temperature, precipitation, local wind speed, population size, vaccination rate and vaccination efficacy. The model was validated using K-fold cross validation as well as forward chaining cross validation and compared to several standard algorithms. Finally, simulation data was generated in R and used for further exploration of the model.
Results We found that temperature is the strongest predictor of ILI rates, but also found that precipitation increased the predictive power of the network. The model was able to outperform comparison models at several prediction points. Additionally, the model accurately predicted simulation data. To test the role of temperature in the network, we phase-shifted temperature in time and found a predictable reduction in prediction accuracy.
Conclusions The results of this study confirm that flu forecasting may be effectively accomplished using architectures traditionally reserved for time series analysis, specifically LSTM-based neural networks. Additionally, this model provided insight into the week-to-week effects of climatic and biotic factors and revealed potential patterns in data series. Specifically, we found that temperature is the strongest predictor of seasonal flu infection rates. This information may prove to be especially important for flu forecasting given the uncertain long-term impact of the SARS-CoV-2 pandemic on seasonal influenza.
Resilience and Its Associations in Children with Systemic Lupus Erythematosus and Juvenile Idiopathic Arthritis
Authors: Trachtman Rebecca , Samuels Julie , Wojtal Emma , Feldman Brian M
Published: May 2023

Background: In this study, we aimed to evaluate resilience and its association with disease activity and health-related quality of life (HRQOL) in children with Systemic Lupus Erythematosus (SLE) and Juvenile Idiopathic Arthritis (JIA).
Findings: Using a cross-sectional design, patients with diagnoses of SLE or JIA were recruited between 8/2019 and 12/2022 in a pediatric rheumatology outpatient setting. At a single study visit we collected: demographic data, medical history and physical examination, physician global health assessment, patient global health assessment, Patient Reported Outcome Measurement Information System questionnaires, Connor Davidson Resilience Scale 10 (CD-RISC 10), Systemic Lupus Erythematosus Disease Activity Index, and clinical Juvenile Arthritis Disease Activity Score 10. Descriptive statistics were calculated. Using standard software, raw scores for PROMIS measures were converted to T-scores. Spearman’s correlations were performed, with statistical significance set to p<0.05.
47 study subjects were recruited. The average CD-RISC 10 score in SLE was 24.4, and in JIA was 25.2. In children with SLE, CD-RISC 10 was correlated with disease activity and inversely correlated with anxiety. In children with JIA, resilience was inversely associated with fatigue, and positively correlated with mobility and peer relationships.
Conclusions: In children with SLE and JIA, resilience is lower than in the general population. Further, our results suggest that interventions to increase resilience may improve the HRQOL of children with rheumatic disease. Ongoing study of the importance of resilience in this population, as well as interventions to increase resilience, will be an important area of future research in children with SLE and JIA.
Direct Relithiation and Efficient Regeneration of Spent LiFePO4 Materials through Thermochemical Healing
Authors: Zhu Yaunyi , Jiao Xiaojuan , Bian Haidong , Lu Xiaoying , Zhang Zheming
Published: May 2023

The environmentally friendly and low-cost recycling of spent LiFePO4 (LFP) cathode materials has become an urgent problem. This paper aims to employ eutectic Li+ molten-salt assisted roasting approach to relithiation and regenerating of spent LFP materials under ambient conditions. Via Li+ compensation and structure reshaping, LiFePO4 cathode material with various degradation conditions can be successfully regenerated, which enables the renovation of the electrochemical performance (the capacity, cycling stability, and rate capability) to the levels of the pristine LFP. It opens a door to the prospect of recycling and remanufacturing degraded cathode materials by this new method, having a strong potential for industrial application.
Is Heavy Metal Pollution in River Ganga: A Risk Factor for Amyotrophic Lateral sclerosis?
Authors: Mishra Bhargawi , Patil Sooraj , Gautam Geeta J. , Gautam Priyanka , Srivast Niraj Kumar , Singh Vineeta , Pathak Abhishek , Singh Varun Kumar , Kumar Anand , Chaurasia R. N. , Joshi Deepika , Mishra Vijaya Nath
Published: May 2023

The association between heavy metals and Amyotrophic Lateral Sclerosis (ALS) patients was explored with respect to the longest and pious Indian river Ganga. This study is designed to investigate the severity and heavy metal contamination in the blood of Gangetic (within 25 km from river Ganga) and non-Gangetic (> 25 km from river Ganga) ALS patients. Out of 65 recruited ALS patients, 36 from the Gangetic belt and 29 from the Non-Gangetic belt. Amyotrophic Lateral Sclerosis functional rating Scale (ALSFRS), Mini-Mental State Examination (MMSE) and Frontal Assessment Battery (FAB) were calculated to study disease progression. Lead (Pb), Manganese (Mn) and Cadmium (Cd) concentrations were estimated in the whole blood of 23 subjects from Gangetic belt, 19 subjects from Non Gangetic belt and 23 heathy controls via Inductively coupled plasma mass spectrometry (ICP-MS) technique. A significantly lower FAB score was obtained in Gangetic patients. Pb concentration was significantly higher in both the diseased group than control and Cd concentration was detected significantly higher in Gangetic ALS patients than non Gangetic patients and control group.
The effect of neuter status on longevity in the Rottweiler dog
Authors: Joone Carolynne Jane , Konovalov Dmitry A.
Published: May 2023

Surgical sterilization or neutering of dogs is a commonly performed procedure in veterinary practices in many countries. In recent decades, concerns have been raised regarding possible side effects of neutering, including increased risk of certain neoplastic, musculoskeletal and endocrinological conditions. Considering that age serves as a significant confounding factor for some of these conditions, evaluating longevity statistics could provide valuable insights into the impact of neutering. The aim of this study was to compare longevity between neutered and sexually intact male and female Rottweilers, using electronic patient records collected by the VetCompass Australia database. Male and female Rottweilers neutered before 4.5 years of age demonstrated an expected lifespan 1.5 years and 1 year shorter, respectively, than their intact counterparts (p < 0.05).Similarly, the sub-population of male and female Rottweilers neutered at some point beyond the age of 4.5 years demonstrated reduced longevity by the age of 7 and 8 years for females and males, respectively, in comparison to their intact counterparts.These findings suggest that neutering has a negative impact on the lifespan of Rottweiler dogs, regardless of the age at which it is performed.
Prediction of osteoporosis in patients with rheumatoid arthritis using machine learning
Authors: Im Hyeonseung , Moon Ki Won , Lee Chaewon , Shin Seunghun , Joo Gihun
Published: May 2023

Osteoporosis is a serious health concern in patients with rheumatoid arthritis (RA). Machine learning (ML) models have been increasingly incorporated into various clinical practices, including disease classification, risk prediction, and treatment response. However, only a few studies have focused on predicting osteoporosis using ML in patients with RA. We aimed to develop an ML model to predict osteoporosis using a representative Korean RA cohort database. The KORean Observational study Network for Arthritis (KORONA) database, established by the Clinical Research Center for RA in Korea, was used in this study. Among the 5,077 patients registered in KORONA, 2,374 patients were included in this study. Four representative ML algorithms were used for the prediction: logistic regression (LR), random forest, XGBoost (XGB), and LightGBM. The accuracy, F1 score, and area under the curve (AUC) of each model were measured. AUC was the highest in the LR group at 0.750, and accuracy was the highest in the XGB group at 0.682. Body mass index, age, menopause, waist and hip circumferences, RA surgery, and monthly income were risk factors of osteoporosis. In conclusion, ML algorithms are a useful option for screening for osteoporosis in patients with RA.
Perspectives of health professionals and patients on implementation of a predictive model of response to immunotherapies in advanced melanoma
Authors: Salam Rehana A , Gide Tuba N , Cust Anne E , Scolyer Richard A , Long Georgina V , Silva Ines P da , Ferguson Peter , Mann Graham J , Watts Caroline , Wilmott James S , Smith Andrea L
Published: May 2023

Background
Immunotherapies have significantly improved the overall survival for patients with advanced melanoma. However, almost half of such patients either do not respond to the therapy or develop resistance to it, subjecting patients to ineffective treatments and unnecessary costs. Predictive biomarker testing can ensure that the patient receives the most effective therapy thereby reducing costs and toxicities. This study was conducted prior to and alongside a clinical validation study of routine predictive biomarker testing for patients with advanced melanoma to gain an insight into the factors associated with successful implementation of this intervention.
Methods
We conducted semi-structured interviews (n=25) with health professionals and patients guided by the EPIS (Exploration, Preparation, Implementation, and Sustainment) framework to understand enablers and barriers of implementation. Data analysis involved inductive and deductive thematic analysis using the Consolidated Framework for Implementation Research (CFIR).
Results
Health providers and patients consistently reported ‘clinical utility of predictive biomarker test’ as a major enabler, recognising that an effective test would assist in identifying likely non-responders and consequently avoid the side effects and other costs of ineffective treatment. Trust in data scientists, adaptability of the test platform, pre-existing organisational infrastructure, and supportive organisational implementation culture were also identified as factors that would support implementation. Lack of validated predictive biomarkers, resources and costs required to implement the test, and health providers’ knowledge, beliefs and concerns around the test were the principal factors that would impede implementation.
Conclusion
This study identifies factors influencing implementation of biomarkers as predictors of treatment response to immunotherapy for melanoma and potential strategies to overcome barriers impeding their transition from discovery to the clinic.
Xenon postconditioning attenuates neuronal injury after spinal cord ischemia/reperfusion injury by targeting endoplasmic reticulum stress- associated apoptosis
Authors: Luo Lan , Wang Yuqing , Tong Jiaqi , Li Lu , Zhu Yanbing , Jin Mu
Published: May 2023

Purpose: To explore the underlying mechanisms of xenon (Xe) protect against spinal cord ischemia/reperfusion injury (SCIRI).
Materials and methods: A SCIRI rat model was induced by abdominal artery occlusion for 85 min and reperfusion. Xe postconditioning (50% Xe) was administered 1 h after 1 h of reperfusion. At reperfusion time points (2, 4, 6, and 24 h), rats were treated with spinal cord scans by MRI to assess the time of peak spinal cord injury after SCIRI. Subsequently, endoplasmic reticulum (ER) stress inhibitor sodium 4-phenylbutyrate (4-PBA) was administered by daily intraperitoneal injection (50 mg/kg) for 5 days before SCIRI. At 4 hours after reperfusion, motor function, immunofluorescence staining, hematoxylin and eosin (HE) staining, Nissl staining, TUNEL staining, real-time reverse transcription polymerase chain (RT-PCR) reaction, and Western blot analyses were performed to investigate the protective effects of Xe against SCIRI.
Results: In the rat I/R model, spinal cord edema peaked at reperfusion 4 h. SCIRI activated ER stress, which was located in neurons. Xe postconditioning remarkably alleviated hind limb motor function, reduced neuronal apoptosis rate, increased the number of normal neurons, inhibited the expression of ER stress related protein in spinal cord. Furthermore, administration of the ER stress inhibitor 4-PBA strongly decreased ER stress-induced apoptosis following SCIRI.
Conclusions: Xe postconditioning inhibits ER stress activation, which contributes to alleviate SCIRI by suppressing neuronal apoptosis.
Macrophage-derived extracellular DNA initiates heterotopic ossification
Authors: Han Xiaoxiao , Gao Changhe , Lu Weicheng , Yan Jianfei , Xu Haoqing , Guo Zhenxing , Qin Wenpin , Lu Naining , Gao Jialu , Zhu Weiwei , Fu Yutong , Jiao Kai
Published: May 2023

Heterotopic ossification (HO) severely affects people's lives; however, its pathological mechanism remains poorly understood. Although extracellular DNA (ecDNA) has been shown to play important roles in pathological calcification, its effects in HO development and progression remain unknown. The in vivo rat Achilles tendon injury model and in vitro collagen I calcification model were used to evaluate the effects of ecDNA in the ectopic calcifications and the main cell types involved in those pathological process. Histology, immunofluorescent staining, reverse transcriptase-polymerase chain reaction analysis and micro-computed tomography were used to identify the distribution of macrophage-derived ecDNA and elucidate their roles in HO. The results showed that the amount of ecDNA and ectopic calcification increased significantly and exhibited a strong correlation in the injured tendons of HO model compared with those of the controls, which was accompanied by a significantly increased number of M2 macrophages in the injured tendon. During in vitro co-culture experiments, M2 macrophages calcified the reconstituted type I collagen and ectopic bone collected from the injured tendons of HO rats, while those effects were inhibited by deoxyribonuclease. More importantly, deoxyribonuclease reversed the pathological calcification in the injured rat tendon HO model. The present study showed that ecDNA from M2 macrophages initiates pathological calcification in HO, and the elimination of ecDNA might be developed into a clinical strategy to prevent ectopic mineralization diseases. The use of deoxyribonuclease for the targeted degradation of ecDNA at affected tissue sites provides a potential solution to treat diseases associated with ectopic mineralization.
Anti-leukemia effects of Omipalisib in Acute Myeloid Leukemia: inhibition of PI3K-AKT-mTOR signaling and suppression of Mitochondrial Biogenesis
Authors: Lin Liang-In , Tseng Chi-Yang , Fu Yu-Hsuan , Ou Da-Liang , Lu Jeng-Wei , Hou Hsin-An
Published: May 2023

Omipalisib (GSK2126458), a potent dual PI3K/mTOR inhibitor, is reported to exhibit anti-tumor effect in several kinds of cancers. More than 50% of acute myeloid leukemia (AML) patients display a hyperactivation of PI3K/AKT/mTOR signaling. We investigated the anti-proliferative effect of omipalisib in AML cell lines with varied genetic backgrounds. The OCI-AML3 and THP-1 cell lines had a significant response to omipalisib, with IC50 values of 17.45 nM and 8.93 nM, respectively. We integrated transcriptomic profile and metabolomic analyses, and followed by gene set enrichment analysis (GSEA) and metabolite enrichment analysis. Our findings showed that in addition to inhibiting PI3K/AKT/mTOR signaling and inducing cell cycle arrest at the G0/G1 phase, omipalisib also suppressed mitochondrial respiration and biogenesis. Furthermore, omipalisib downregulated several genes associated with serine, glycine, threonine, and glutathione metabolism, and decreased their protein and glutathione levels. In vivo experiments revealed that omipalisib significantly inhibited tumor growth and prolonged mouse survival without weight loss. Gedatolisib and dactolisib, another two PI3K/mTOR inhibitors, exerted similar effects without affecting mitochondria biogenesis. These results highlight the multifaceted anti-leukemic effect of omipalisib, revealing its potential as a novel therapeutic agent in AML treatment.