bluuebunny/crossref_metadata_2025_split huggingface dataset:
Remnant cholesterol is an additional risk factor for cardiovascular disease beyond LDL cholesterol; Nationwide cohort study
Authors: Jung Han Na , Huh Ji Hye , Han Kyung-Do , Roh Eun , Kang Jun Goo , Lee Seong Jin , Ihm Sung-Hee 
Published: June 2023

Abstract
Background
Although elevated remnant cholesterol (remnant-C) level is considered an independent predictor of cardiovascular disease (CVD), it was not established in relatively healthy individuals. We investigated whether elevated remnant-C is a risk factor for CVD in the general population.
Methods
In total 8,874,254 Korean adults with unknown history of CVD were recruited in 2009 and followed until the date of incident myocardial infarction (MI) or ischemic stroke or December 31, 2018. Multivariate Cox regression models were used to estimate the risk for incident CVD associated with remnant-C.
Results
There were 184,771 individuals with incident CVD consisting of MI and ischemic stroke during 8.3 years of follow-up. The adjusted hazard ratios in the highest quartile of remnant-C were 1.681 (95% confidence interval, 1.636–1.726) for MI and 1.433 (1.407–1.46) for stroke. This pattern persisted when patients were stratified by age, sex, statin or fibrate use, and other cholesterol levels. Increased risk of MI or stroke owing to high concentrations of remnant-C was profound in patients with fewer traditional CVD risks (e.g. young age, women, non-obese, and those without hypertension, metabolic syndrome, chronic kidney disease, and diabetes). A remnant-C level ≥ 30 mg/dL was associated with an increased risk of CVD regardless of low-density lipoprotein cholesterol (LDL-C) levels being on target (LDL-C < 100mg/dL).
Conclusions
Elevated remnant-C is associated with an increased risk of CVD independent of traditional risk factors, including LDL-C. This finding suggests that remnant-C is an important CVD risk factor even in individuals with relatively low risk of atherosclerotic cardiovascular disease.
Certification of novel lncRNA based on analysis of ceRNA network in digestive system pan-cancer and characteristics of tumor immune microenvironment
Authors: He Zikang , Liang Shuang , Li Guoli , Wang Xueyan , Shen Ping , Wang Huan , Cui Rongjun 
Published: June 2023

AbstractBackground:Based on analysis of competitive endogenous RNA (ceRNA) and immune microenvironment, we screened their specific Long non-coding RNA (lncRNA) from the perspective of digestive system pan-cancer, and performed preliminary experimental validation.Methods:The transcriptome data of were downloaded from The Cancer Genome Atlas (TCGA) database, including esophageal carcinoma(ESCA), stomach adenocarcinoma (STAD), colorectal carcinoma (CRC) and liver hepatocellular adenocarcinoma (LIHC). We screened and predicted co-expressed differentially lncRNAs, miRNAs, and mRNAs of four tumors using R language. CeRNA networks were constructed by Cytoscape software.LASSO and Cox regression analysis were used to construct prognostic model. The application value of the prognostic model was assessed by combining clinicopathological features. The relationship between prognostic models and immune micro-environment was evaluated using Wilcoxon signed rank test. CCK8, scratch and Transwell assays were performed to analyze the effects of overexpression of lncRNA on CRC cells lines SW837 and SW620. The effect of overexpression of lncRNA on target proteins was detected using western blot.Results:Co-expressed lncRNAs 256, miRNAs 36, mRNAs 921 were obtained to construct the ceRNA network. LncRNA (WDFY3-AS2 and HOTAIR), miRNA (hsa-miR-21), and mRNA (OSR1) were screened using LASSO and Cox regression analysis to construct prognostic model. The survival rate of patients in the low-risk group was better than that in the high-risk group (P<0.001). The risk score and clinical stage could be used as independent prognostic factors for the digestive system pan-cancer. The risk score was positively correlated with the infiltration of multiple immune cells. The high-risk groups of CRC and LIHC were positively correlated with the expression of CD274, CTLA4, PDCD1, and HAVCR2 (P<0.05). Cellular experiments showed that the overexpression of WDFY3-AS2 reduced the survival rates of colorectal cancer cells, increased the healing time of scratched cells, and decreased the passage rate of transwell cells. Western blot assay suggested that WDFY3- AS2 can positively regulated the expression of OSR1.Conclusions:The prognostic model constructed based on the WDFY3-AS2/HOTAIR /hsa-miR-21/OSR1 ceRNA regulatory axis was able to assess the prognosis of pan-cancer of the digestive system, and the specific LncRNA WDFY3-AS2 inhibited the proliferation, invasion and metastasis of colon cancer cells.
Uncovering the Neuroprotective Effect of Vitamin B12 in Pneumococcal Meningitis: Insights into Its Pleiotropic Mode of Action at the Transcriptional Level
Authors: Cassiano Larissa Marcely Gomes , Oliveira Marina da Silva , Queiroz Karina Barbosa , Amancio Alice Muglia Thomaz da Silva , Salim Anna Christina de Matos , Fernandes Gabriel da Rocha , Carneiro Cláudia Martins , Coimbra Roney Santos 
Published: June 2023

Abstract
Background
The interplay between bacterial virulence factors and the host innate immune response in pneumococcal meningitis (PM) can result in uncontrolled neuroinflammation, which is known to induce apoptotic death of progenitor cells and post-mitotic neurons in the hippocampal dentate gyrus, resulting in cognitive impairment. Vitamin B12 attenuates hippocampal damage and reduces the expression of some key inflammatory genes in PM, by acting as an epidrug that promotes DNA methylation, with increased production of S-adenosyl-methionine, the universal donor of methyl.
Objective
This study aimed to investigate the effects of adjuvant therapy with vitamin B12 on microglial activation, inflammatory infiltrate within the central nervous system, as well as the hippocampal transcriptome and histone markings in infant rats with PM
Material and Methods
Elven-day-old rats were infected with S. pneumoniae via intracisternal injection and then administered either vitamin B12 or a placebo. After 24 hours of infection, the animals were euthanized, and apoptosis in the hippocampal dentate gyrus, microglia activation, and the inflammatory infiltrate were quantified in one brain hemisphere. The other hemisphere was used for RNA-Seq and RT-qPCR analysis.
Results
In this study, adjuvant therapy with B12 was found to modulate the hippocampal transcriptional signature induced by PM in infant rats, mitigating the effects of the disease in canonical pathways related to the recognition of pathogens by immune cells, signaling via NF-kB, production of pro-inflammatory cytokines, migration of peripheral leukocytes into the central nervous system, and production of reactive species. Phenotypic analysis revealed that B12 effectively inhibited microglia activation in the hippocampus and reduced the inflammatory infiltrate in the central nervous system of the infected animals. These pleiotropic transcriptional effects of B12 that lead to neuroprotection are partly regulated by alterations in histone methylation markings. No adverse effects of B12 were predicted or observed, reinforcing the well-established safety profile of this epidrug.
Conclusion
B12 effectively mitigates the impact of PM on pivotal neuroinflammatory pathways. This leads to reduced microglia activation and inflammatory infiltrate within the central nervous system, resulting in the attenuation of hippocampal damage. The anti-inflammatory and neuroprotective effects of B12 involve the modulation of histone markings in hippocampal neural cells.
Stochastic equilibrium of free trade under a FIGARCH volatility
Authors: boughabi houssam 
Published: June 2023

Abstract
Free trade for some economists gains so much attention, the horrible thing is though when a nation doesn't knit relations with other countries because this would harm the future gains almost if land or property is rare: what i had tried to mention is the importance of free trade as far as consumption is concerned, if the national tissue is almost based upon expenditures that's a farce, more than a farce; it's a black resort getting economists warry about the well being of their nations.
I had resolved for a complicated situation when almost no free trade is alive, when i give consumption as a benchmark for welfare.
Afterward i had dived into debt when proposing a model for the level of debt that takes in ation into account; just after we got a numerical resolution for the behavior of our model. Under the absence of arbitrage i have made an approximation that looks great for econometrics and finance.
JEL Classification. B27, C01.
KEZUHUDAN ISA AL-MASIH DALAM KITAB AL-ZUHD WA’L-RAQĀ’IQ DAN AL-ZUHD
Authors: Muhammad Hasyim 
Published: June 2023

The ascetisc of Isa al-Masih is the most polular model in strengtening the ascetism doctrines among tasawwuf experts in clasical periods. At least it was depicted in clasical sunnite sufism that narrated the messages and stories about the escatism of Isa al-Masih. Above all, the more valid source, i.e. al-Qur’an and al-hadits are more than enough to strengten the doctrine of ascetism for the tasawwuf experts (sufi). Ascetism of Isa al-Masih was conformable to the concept of ascetismof the sufi, which meant that have nothing and belong to nothing (lā yamliku shaian walā yamlikuhu shaiun). Ascetism is not only merely spiritual position which is depicted in tasawuf, but ascetisme in this context is the spiritual it self.***Asketisme Isa al-Masih merupakan model yang paling populer dalam mem­perkuat doktrin asketisme di kalangan ahli tasawuf dalam periode klasik. Setidaknya itu digambarkan dalam sufisme sunni klasik yang menarasikan pesan dan kisah mengenai asketisme Isa al-Masih. Di luar itu semua, sumber yang lebih valid, yaitu al-Qur’an dan hadits lebih dari cukup untuk memperkuat doktrin asketisme bag para ahli tasawuf (sufi). Asketisme Isa al-Masih sesuai dengan konsep asketisme sufi yang artinya tidak memiliki apa-apa dan bukan milik siapa-siapa (lā yamliku shaian walā yamliku shaiun). Asketisme bukan sekedar posisi spiritual yang digambarkan di dalam tasawuf, tetapi asketisme dalam konteks ini adalah spiritual itu sendiri.
PENGALAMAN BERSUA TUHAN: PERSPEKTIF WILLIAM JAMES DAN AL-GHAZALI
Authors: Komarudin Komarudin 
Published: June 2023

Experience of meeting God constitutes an interresting phenomenon and become the focus of interrest of many disciplines. Psychology and tasawuf are two disciplines which focusedly study this phenomenon applying different approaches. Ghazali is the representative of the dicsipline of tasawwuf and William James is the representative of the dicsipline of psychology. The both experts applied the different approaches in studying the religious experiences. Epistemological base on which William James used , has the scientific accountability but less accurate in the source of knowledge. In other side, Ghazali has a deep source of knowledge but less of rationality. An effort to compromise the both approach in order to study about the experience of meeting God will result in a comprehensive, deep, and objective depiction.***Pengalaman bersua Tuhan merupakan fenomena yang menarik dan menjadi titik perhatian banyak disiplin ilmu. Psikologi dan tasawuf merupakan dua disiplin ilmu yang memfokuskan kajiannya pada fenomena ini dengan menerapkan pendekatan yang berbeda. Ghazali adalah representasi dari disiplin ilmu tasawuf dan William James adalah representasi disiplin ilmu psikologi. Kedua ahli tersebut menggunakan pendekatan yang berbeda dalam mengkaji pengalaman keagamaan. Basis epistimologi yang digunakan oleh James memiliki akuntabilitas ilmiah namun kurang akurat dalam sumber pengetahuannya. Di sisi lain Ghazali memiliki sumber pengetahuan yang dalam namun kurang dari sisi rasionalitas. Upaya untuk mengkompromikan kedua pendekatan dalam rangka untuk mengkaji pengalaman bersua Tuhan akan menghasilkan penggambaran yang dalam dan obyektif.
POLITIK DAKWAH DAN DAKWAH POLITIK DI ERA REFORMASI INDONESIA
Authors: Rosa Andi 
Published: June 2023

This research activity parse dzikir majelis Susilo Bambang Yudhoyono (SBY) "Nurussalam" which has a strategic role in the democratic era. His status as a society organizations (NGOs) are positioned optimally by interest groups, political organizations and even into the container. By analyzing the dataobtained through interviews and documentation, the results of this study indicate that this council makes verses of the Qur’an that deals with the concept of al-‘ummah, al-ukhuwwah al-islamiyya, and al-ta'āwun as a cornerstone in interpreting para­graph integrative social which is then used as a propaganda entity. Proselytizing as mass communication, political communication line with more likely to use communication as a way to mobilize the masses massif. Even activities have been able to carry out the functions of political propaganda as part of the interest-group system.
MULTIKULTURALISME DAN HEGEMONI POLITIK PERNIKAHAN ENDOGAMI: IMPLIKASI DALAM DAKWAH ISLAM
Authors: Rahmaniah Syarifah Ema 
Published: June 2023

This paper described a variety of views on the dynamics of endogamy marriage practiced by sharif community in Pontianak. This paper used the theory of hege­mony to analyze Surah al-Ahzab: 33 as the cause of endogamy among the descendants of 'Isa al-Muhajir (Ba ‘Alawi) that have migrated to the archipelago. One of her off spring grew and spread in Pontianak was called sharif or syarifah of Pontianak. The results of this study explained that there are three different attitudes about endogamous marriage, they are accept, reject and moderate thinking. The three different attitudes came out as the result of modernization, contact with foreign cultures, the influence of education, socio-economic, and the existing settlement pattern. There is a socio-political implications of the verses of hegemony that is keeping the values of the potential political kinship as social capital to raise awareness and political culture in the context of community participation and representation of sharif in local and national politics. But in sociocultural context. Once endogamy was understood as an absolute system that must be run so it may open space of social stratification that threatens women’s freedom and will open the spaces for subordination.
Novel bone Morphogenetic Protein (BMP)-2/4 Consensus Peptide (BCP)
for the Osteogenic Differentiation of C2C12 Cells
Authors: Hwang Jin Wook , Han Youn Ho 
Published: June 2023

Background:
Despite the promising clinical potential of bone morphogenetic protein
(BMP)-related therapies for bone formation, their side effects warrant the need for alternative therapeutic
peptides. BMP family members can aid in bone repair; however, peptides derived from BMP2/
4 have not yet been investigated.

Methods:
In this study, three candidates BMP2/4 consensus peptide (BCP) 1, 2, and 3 were identified
and their ability to induce osteogenesis in C2C12 cells was analyzed. First, an alkaline phosphatase
(ALP) staining assay was performed to evaluate the osteogenic effects of BCPs. Next, the
effects of BCPs on RNA expression levels and protein abundances of osteogenic markers were explored.
Furthermore, the transcriptional activity of ALP by BCP1 and in silico molecular docking
model on BMP type IA receptor (BRIA) were performed.

Results:
BCP1-3 induced higher RUNX2 expression than BMP2. Interestingly, among them,
BCP1 significantly promoted osteoblast differentiation more than BMP2 in ALP staining with no
cytotoxicity. BCP1 significantly induced the osteoblast markers, and the highest RUNX2 expression
was observed at 100 ng/mL compared to other concentrations. In transfection experiments,
BCP1 stimulated osteoblast differentiation via RUNX2 activation and the Smad signaling pathway.
Finally, in silico molecular docking suggested the possible binding sites of BCP1 on BRIA.

Conclusion:
These results show that BCP1 promotes osteogenicity in C2C12 cells. This study
suggests that BCP1 is the most promising candidate peptide to replace BMP2 for osteoblast differentiation.
Deep-RPA: Vulnerability Classification of a Genome for CRISPR/Cas9 Off-targets
Authors: Saddique Tausif Ur Rehman , Saloum Said S. , Razzaq Abdul , Husain Aamir , Baig Irfan Ahmad , Ali Zulqurnain , Khan Zulqurnain 
Published: June 2023

Background:
Researchers working in genome engineering are making fast strides to precising the techniques of site-specific gene editing. CRISPR-Cas (Clustered Regularly Interspaced Short Palindromic Repeats) is one of the most recent gene editing techniques. It consists of a Cas9 nuclease and a single guided RNA (sgRNA) that targets DNA at the required target site. Consequently, along with on-targets, genomes may also have multiple off-targets, which is a potential drawback of gene editing techniques. Lab-based assays are used to examine the off-target effects of sgRNA. This challenge makes the technique questionable in terms of cost, time and efficacy. Deep learning techniques have been used efficiently to analyze biological data and calculate off-target sites in the genome.
This research aims to identify CRISPR off-targets within the genome as well as predict genome vulnerability for unexpected mutations using a deep learning approach.

Method:
This study presents a two-step data preprocessing and off-target prediction method that may be used to determine genome instability. A raw DNA sequence was initially preprocessed and subdivided into 20-bp long multiple substrings. These substrings were further categorized into perfect matches and mismatches. Secondly, average weights were assigned based on the CFD (Cutting Frequency Determination) of the off-targets that showed the genome's vulnerability. Finally, the deep neural network model was trained using random genomic data. To identify off-targets and predict genome vulnerability, a Deep-RPA model was trained and tested on the DNA sequence of the Arabidopsis model plant.

Results:
The results demonstrated the accuracy and validity of Deep-RPA by accurately predicting off-targets and genome vulnerabilities on different sample sequences. The proposed model was evaluated through stratified five-fold cross-validation, which attained an average accuracy of 99 percent for predicting genome vulnerability. The results illustrated satisfactory improvement compared to existing solutions.

Conclusion:
The proposed design using a 1D CNN has shown significant improvement in text-based sequence analysis and has outperformed current methods by a wide margin.
ПРОФІЛАКТИКА ТА КОРЕКЦІЯ ТИРЕОЇДНОЇ ДИСФУНКЦІЇ У ПІДЛІТКІВ ІЗ ЦУКРОВИМ ДІАБЕТОМ 1 ТИПУ НА ЕТАПАХ СТАТЕВОГО ДОЗРІВАННЯ
Authors: Турчина Світлана , Костенко Тетяна , Нікітіна Лариса , Вародова Ольга , Косовцова Ганна , Чумак Світлана , Шушляпіна Олена , Філіппова Неоніла , Левчук Людмила , Юдченко Ольга 
Published: June 2023

Мета дослідження – удосконалити методи профілактики та лікування порушень функціонального стану гіпофізарно-тиреоїдної системи у підлітків, хворих на цукровий діабет 1 типу (ЦД1).
Матеріали та методи. Обстежено 114 пацієнтів із ЦД1 у віці 9-16 років (основна група) та 149 практично здорових однолітків (група порівняння). У всіх підлітків у сироватці крові імуноферментним методом визначено рівень тиреотропіну (ТТГ), вільних фракцій тиреоїдних гормонів (fT4 і fT3) та розраховано їх співвідношення (fT3/fT4 та ТТГ/fТ4). Аналіз отриманих показників проведено з урахуванням рівня статевого розвитку підлітків.
Результати обстеження об’єднано в електронний банк даних, математична обробка яких була проведена за допомогою пакетів програм «SPSS Statistics 17,0», «Microsoft Excel-2007». Критичний рівень значущості для перевірки статистичних гіпотез приймався рівним 0,05.
Результати. У підлітків обох груп на початку статевого дозрівання відбувається збільшення рівня ТТГ на тлі зменшення рівня fТ4 та збільшення співвідношення ТТГ/fТ4. Показники співвідношень ТТГ/fТ4 та fТ3/fТ4 були вірогідно більшими у хворих на ЦД1, ніж в групі порівняння.
При індивідуальному аналізі встановлено, що ознаки тиреоїдной недостатності найчастіше визначали в період раннього пубертату серед підлітків обох груп (60,0% серед хворих на ЦД1 та 43,9% – в групі порівняння, p<0,05). На всіх етапах статевого дозрівання частота пацієнтів із гіпотиреозом була вірогідно більшою серед підлітків із ЦД1, ніж в групі порівняння (препубертат:16,0% проти 6,6%, p<0,05, ранній пубертат: 23,5% проти 0%, p<0,05, власно пубертат: 8,9% проти 2,9%, p<0,05). Обґрунтовано включення до схеми лікування препаратів калію йодиду (препарат ЙодомаринÒ 100 або препарат ЙодомаринÒ 200) та левотироксину (L-Тироксин Берлін-Хемі) при профілактики та лікування тиреоїдної дисфункції.
Висновки. У підлітків із ЦД1 вірогідно збільшується відсоток хворих, які мають ознаки тиреоїдної дисфункції завдяки підвищенню рівня ТТГ на тлі зменшення показників fТ4 та збільшення fТ3. Найчастіше ознаки тиреоїдної недостатності діагностують в період раннього пубертату. Профілактика та корекція тиреоїдної дисфункції є обов'язковою складовою реабілітаційної програми дітей та підлітків із цукровим діабетом 1 типу.
The Impact of Agricultural Credit on Banana cultivation in Valle del Cauca, Colombia
Authors: Rivera-Acosta Javier , Xiuchuan Xu 
Published: June 2023

This study aimed to explore the use and effect of agricultural credit disbursed from banks and financial institutions on banana yield in farmers from Valle del Cauca (Colombia) using data from the National Agricultural Census (2014). Additionally, it evaluated whether the effect of credit differs according to the items in which the farmer prefers to invest. For this purpose, because credits are not granted randomly, this research used the Propensity Score Matching (PSM) methodology to manage selection bias. Initially, it was found through the probit model that having one's own agricultural machinery, using chemical fertilization to improve soil fertility, not belonging to an ethnic minority, and having some type of basic or higher education, increases the probability of obtaining an agricultural credit. On the other hand, the results suggest that credit has positive and significant effects on crop yield (6.2%), but the effect is greater if it is invested in land purchase and post-harvest processes, with an increase of 39% and 37% in yield, respectively. On the other hand, this study also suggests that, if credit is invested in items not related to agricultural activity, yields can be affected with a 10% reduction. Finally, it is recommended that a public policy be implemented to encourage greater participation of banana farmers in Valle del Cauca in agricultural credit programs, given their low participation (10%) despite the high acceptability rate (86%).
Bridging the Gap: Design Suggestions and Remediation Insights from a Curriculum Change in the Financial Accounting Series
Authors: Brockbank Bryan G. , Sisneros Craig A. , Spencer Angela Wheeler , Stroud W. Adam 
Published: June 2023

ABSTRACT
As part of a revision to the undergraduate business core curriculum, the typical two-course introductory series was condensed into one class, and an additional “bridge” course was created for students continuing to intermediate accounting. The transition period created a natural experiment to examine student success and retention in intermediate accounting and beyond. Compared with students who had completed six hours of principles courses and a gateway exam, students who completed this new course sequence scored higher on an incoming assessment in the new and more advanced first intermediate course. Further, the performance advantage is evident in higher exam grades in the first intermediate course, higher GPA in future accounting courses, greater retention of accounting majors, and gains in conversion to accounting. Although this curriculum change is somewhat unique, the results lend insights to accounting educators on how to address success and retention/gains of accounting students throughout intermediate accounting and beyond.