bluuebunny/crossref_metadata_2025_split huggingface dataset:
First report of Serotype-1 Marek’s disease virus (MDV-1) with oncogenic form in backyard turkeys in Turkey: a molecular analysis study
Authors: Ongor Hasan , Timurkaan Necati , Abayli Hasan , Karabulut Burak , Kalender Hakan , Tonbak Sukru , Eroksuz Hatice , Çetinkaya Burhan 
Published: January 2022

Abstract
Background
Marek’s disease (MD) is a lymphoproliferative disease caused by Gallid alphaherpesvirus 2 (GaHV-2, MDV-1), which primarily affects chickens. However, the virus is also able to induce tumors and polyneuritis in turkeys, albeit less frequently than in chickens.

Results
This is the first study in Turkey reporting the molecular characterization of a MDV-1 strain detected in a flock of backyard turkeys exhibiting visceral lymphoma. Here, MEQ, vIL-8, pp38 and 132-bp tandem repeat regions, which are frequently preferred in the pathotyping of MDV-1, were examined. It was determined that the MEQ gene of MDV-1/TR-21/turkey strain obtained in the present study encoded 339 amino acids (1020 nt) and had four proline-rich repeat regions (PPPP). Based on the nucleotide sequence of the MEQ gene of the MDV-1/TR-21/turkey strain, a phylogenetic tree was created using the MEGA-X software with the Maximum Likelihood Method (in 1000 replicates). Our strain was highly identical (> 99.8) to the Italian/Ck/625/16, Polish (Polen5) and some Turkish (Layer-GaHV-2-02-TR-2017, Tr/MDV-1/19) MDV-1 strains. Also, nt and aa sequences of the MEQ gene of our strain were 99.1 and 99.41% identical to another Turkish strain (MDV/Tur/2019) originated from chickens. Sequence analysis of pp38 and vIL-8 genes also supported the above finding. The identity ratios of nucleotide and amino acid sequences of vIL-8 and pp38 genes of MDV-1/TR-21/turkey strain were 99.64–100% and 99.79–100%, respectively, when compared with those of the Polish strain. According to 132-bp tandem repeat PCR results, the MDV-1/TR-21/turkey strain had five copies.

Conclusions
These results suggested that the MDV-1/TR-21/turkey strain obtained from backyard turkeys can be either very virulent or very virulent plus pathotype, though experimental inoculation is required for precise pathotyping.
The role of m6A RNA methylation in cancer metabolism
Authors: An Yuanyuan , Duan Hua 
Published: January 2022

AbstractMetabolic reprogramming is one of the main characteristics of malignant tumors, which is due to the flexible changes of cell metabolism that can meet the needs of cell growth and maintain the homeostasis of tissue environments. Cancer cells can obtain metabolic adaptation through a variety of endogenous and exogenous signaling pathways, which can not only promote the growth of malignant cancer cells, but also start the transformation process of cells to adapt to tumor microenvironment. Studies show that m6A RNA methylation is widely involved in the metabolic recombination of tumor cells. In eukaryotes, m6A methylation is the most abundant modification in mRNA, which is involved in almost all the RNA cycle stages, including regulation the transcription, maturation, translation, degradation and stability of mRNA. M6A RNA methylation can be involved in the regulation of physiological and pathological processes, including cancer. In this review, we discuss the role of m6A RNA methylation modification plays in tumor metabolism-related molecules and pathways, aiming to show the importance of targeting m6A in regulating tumor metabolism.
Extracellular vesicles derived from glioblastoma promote proliferation and migration of neural progenitor cells via PI3K-Akt pathway
Authors: Pan Jiabin , Sheng Shiyang , Ye Ling , Xu Xiaonan , Ma Yizhao , Feng Xuanran , Qiu Lisha , Fan Zhaohuan , Wang Yi , Xia Xiaohuan , Zheng Jialin C. 
Published: January 2022

Abstract
Background
Glioblastomas are lethal brain tumors under the current combinatorial therapeutic strategy that includes surgery, chemo- and radio-therapies. Extensive changes in the tumor microenvironment is a key reason for resistance to chemo- or radio-therapy and frequent tumor recurrences. Understanding the tumor-nontumor cell interaction in TME is critical for developing new therapy. Glioblastomas are known to recruit normal cells in their environs to sustain growth and encroachment into other regions. Neural progenitor cells (NPCs) have been noted to migrate towards the site of glioblastomas, however, the detailed mechanisms underlying glioblastoma-mediated NPCs’ alteration remain unkown.

Methods
We collected EVs in the culture medium of three classic glioblastoma cell lines, U87 and A172 (male cell lines), and LN229 (female cell line). U87, A172, and LN229 were co-cultured with their corresponding EVs, respectively. Mouse NPCs (mNPCs) were co-cultured with glioblastoma-derived EVs. The proliferation and migration of tumor cells and mNPCs after EVs treatment were examined. Proteomic analysis and western blotting were utilized to identify the underlying mechanisms of glioblastoma-derived EVs-induced alterations in mNPCs.

Results
We first show that glioblastoma cell lines U87-, A172-, and LN229-derived EVs were essential for glioblastoma cell prolifeartion and migration. We then demonstrated that glioblastoma-derived EVs dramatically promoted NPC proliferation and migration. Mechanistic studies identify that glioblastoma-derived EVs achieve their functions via activating PI3K-Akt-mTOR pathway in mNPCs. Inhibiting PI3K-Akt pathway reversed the elevated prolfieration and migration of glioblastoma-derived EVs-treated mNPCs.

Conclusion
Our findings demonstrate that EVs play a key role in intercellular communication in tumor microenvironment. Inhibition of the tumorgenic EVs-mediated PI3K-Akt-mTOR pathway activation might be a novel strategy to shed light on glioblastoma therapy.
The role and possible mechanism of the long noncoding RNA LINC01260 in nonalcoholic fatty liver disease
Authors: Ge Xiaoxiao , Sun Tao , Zhang Yanmei , Li Yongqing , Gao Peng , Zhang Dantong , Zhang Bingyang , Wang Peijun , Ma Wanshan , Lu Sumei 
Published: January 2022

Abstract
Objective
To investigate the differential expression profile of lncRNAs in the nonalcoholic fatty liver disease (NAFLD) model induced by oleic acid (OA) and to further explore the role of LINC01260 (ENST00000255183) in NAFLD, providing theoretical support for the clinical value of lncRNAs in NAFLD.

Methods
OA (50 μg/mL) was used to induce steatosis in normal human LO2 hepatocytes for 48 h and was verified by Oil red O staining. Differential expression profiles of lncRNAs were obtained by eukaryotic circular sequencing (RNA/lncRNA/circRNA-seq) techniques. A gain-of-function (GOF) strategy for LINC01260 was adopted, Oil red O staining and semiquantitative analysis were combined to explore whether the GOF of LINC01260 affects LO2 cell steatosis. CeRNA-based bioinformatics analysis of lncRNAs was performed, and the enriched mRNAs were further verified. RXRB siRNAs were applied and verify its role in LINC01260 regulated OA-induced hepatocytes steatosis.

Results
Lipid droplets of different sizes were observed in the cells of the OA group. Absorbance in the OA group was significantly increased after isopropanol decolorization (P < 0.05). Compared with those in the control group, there were 648 lncRNAs with differential expression greater than 1 time in the OA group, of which 351 were upregulated and 297 were downregulated. Fluorescence quantitative PCR showed that the expression of LINC01260 in the OA group was downregulated by 0.35 ± 0.07-fold (P < 0.05). The formation of lipid droplets in LO2 cells of the LINC01260 GOF group decreased significantly (P < 0.05). CeRNA analysis indicated that the mRNA levels of RXRB, RNPEPL1, CD82, MADD and KLC2 were changed to different degrees. Overexpression of LINC01260 significantly induced RXRB transcription (P < 0.05) and translation, and RXRB silence attenuated the lipids decrease induced by LINC01260 overexpression.

Conclusion
The OA-induced NAFLD cell model has a wide range of lncRNA differential expression profiles. LINC01260 participates in the regulation of the lipid droplet formation process of NAFLD, and its overexpression can significantly inhibit the steatosis process of LO2 cells. Mechanistically, LINC01260 may act as a ceRNA to regulate the expression of RXRB, thereby affecting the adipocytokine signaling pathway.
A deep generative model for multi-view profiling of single-cell RNA-seq and ATAC-seq data
Authors: Li Gaoyang , Fu Shaliu , Wang Shuguang , Zhu Chenyu , Duan Bin , Tang Chen , Chen Xiaohan , Chuai Guohui , Wang Ping , Liu Qi 
Published: January 2022

AbstractHere, we present a multi-modal deep generative model, the single-cell Multi-View Profiler (scMVP), which is designed for handling sequencing data that simultaneously measure gene expression and chromatin accessibility in the same cell, including SNARE-seq, sci-CAR, Paired-seq, SHARE-seq, and Multiome from 10X Genomics. scMVP generates common latent representations for dimensionality reduction, cell clustering, and developmental trajectory inference and generates separate imputations for differential analysis and cis-regulatory element identification. scMVP can help mitigate data sparsity issues with imputation and accurately identify cell groups for different joint profiling techniques with common latent embedding, and we demonstrate its advantages on several realistic datasets.
Efficacy of repetitive transcranial magnetic stimulation (rTMS) for reducing consumption in patients with alcohol use disorders (ALCOSTIM): study protocol for a randomized controlled trial
Authors: Petit Benjamin , Soudry-Faure Agnès , Jeanjean Ludovic , Foucher Jack , Lalanne Laurence , Carpentier Maud , Jonval Lysiane , Allard Coralie , Ravier Mathilde , Mohamed Amine Ben , Meille Vincent , Trojak Benoit 
Published: January 2022

Abstract
Background
The number of people with an alcohol use disorder (AUD) was recently estimated to be 63.5 million worldwide. The global burden of disease and injury attributable to alcohol is considerable: about 3 million deaths, namely one in 20, were caused by alcohol in 2015. At the same time, AUD remains seriously undertreated.
In this context, alternative or adjunctive therapies such as brain stimulation could play an important role. The early results of studies using repetitive transcranial magnetic stimulation (rTMS) suggest that stimulations delivered to the dorsolateral prefrontal cortex significantly reduce cravings and improve decision-making processes in various addictive disorders. We therefore hypothesize that rTMS could lead to a decrease in alcohol consumption in patients with AUD.

Methods/design
We report the protocol of a randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the efficacy of rTMS on alcohol reduction in individuals diagnosed with AUD. The study will be conducted in 2 centers in France. Altogether, 144 subjects older than 18 years and diagnosed with AUD will be randomized to receive 5 consecutive twice-daily sessions of either active or sham rTMS (10 Hz over the right DLPFC, 2000 pulses per day). The main outcomes of the study will be changes in alcohol consumption within the 4 weeks after the rTMS sessions. Secondary outcome measures will include changes in alcohol consumption within the 24 weeks, alcohol cravings, clinical and biological improvements, effects on mood and quality of life, and cognitive and safety assessments, and, for smokers, an assessment of the effects of rTMS on tobacco consumption.

Discussion
Several studies have observed a beneficial effect of rTMS on substance use disorders by reducing craving, impulsivity, and risk-taking behavior and suggest that rTMS may be a promising treatment in addiction. However, to date, no studies have included sufficiently large samples and sufficient follow-up to confirm this hypothesis. The results from this large randomized controlled trial will give a better overview of the therapeutic potential of rTMS in AUD.

Trial registration
ClinicalTrials.gov NCT04773691. Registered on 26 February 2021
https://clinicaltrials.gov/ct2/show/NCT04773691?term=trojak&draw=2&rank=5.
Comparison of insertion time, pull-out strength, and screw-media interface area of customized pedicle screw with different core and thread design against commercial pedicle screw: a pilot study on Indonesian Population
Authors: Magetsari Rahadyan , Rukmoyo Tedjo , Saputra Marda Ade , Sakti Yudha Mathan 
Published: January 2022

Abstract
Objective
This research aimed to developing customized pedicle screw based on Indonesian vertebral anatomy and compare the insertion time, pull-out strength, and screw-media interface area of different screw design. We have developed 3 different types of pedicle screws (v-thread cylinder-core, square-thread cylinder-core and square-thread conical-core). The thread diameter was calculated from pedicle width of Indonesian population (6 mm). We used commercially available pedicle screw as control group (6.2 mm).

Result
The insertion time were significantly difference between v-thread cylinder-core pedicle screw (22.94 s) with commercially available pedicle screw (15.86 s) (p < 0.05). The pull-out strength was significantly difference between commercially available pedicle screw (408.60 N) with square-thread conical pedicle screw (836.60 N) (p < 0.05). The square-thread conical-core group have the highest interface area (1486.21 mm2). The data comparison showed that the square-thread conical-core customized pedicle screw group has comparable insertion time and has better pull-out strength than commercially available pedicle screw.
Improving low-resource Tibetan end-to-end ASR by multilingual and multilevel unit modeling
Authors: Qin Siqing , Wang Longbiao , Li Sheng , Dang Jianwu , Pan Lixin 
Published: January 2022

AbstractConventional automatic speech recognition (ASR) and emerging end-to-end (E2E) speech recognition have achieved promising results after being provided with sufficient resources. However, for low-resource language, the current ASR is still challenging. The Lhasa dialect is the most widespread Tibetan dialect and has a wealth of speakers and transcriptions. Hence, it is meaningful to apply the ASR technique to the Lhasa dialect for historical heritage protection and cultural exchange. Previous work on Tibetan speech recognition focused on selecting phone-level acoustic modeling units and incorporating tonal information but underestimated the influence of limited data. The purpose of this paper is to improve the speech recognition performance of the low-resource Lhasa dialect by adopting multilingual speech recognition technology on the E2E structure based on the transfer learning framework. Using transfer learning, we first establish a monolingual E2E ASR system for the Lhasa dialect with different source languages to initialize the ASR model to compare the positive effects of source languages on the Tibetan ASR model. We further propose a multilingual E2E ASR system by utilizing initialization strategies with different source languages and multilevel units, which is proposed for the first time. Our experiments show that the performance of the proposed method-based ASR system exceeds that of the E2E baseline ASR system. Our proposed method effectively models the low-resource Lhasa dialect and achieves a relative 14.2% performance improvement in character error rate (CER) compared to DNN-HMM systems. Moreover, from the best monolingual E2E model to the best multilingual E2E model of the Lhasa dialect, the system’s performance increased by 8.4% in CER.
Generalizations of the Jensen functional involving diamond integrals via Abel–Gontscharoff interpolation
Authors: Bibi Rabia , Nosheen Ammara , Bano Shanaz , Pečarić Josip 
Published: January 2022

AbstractIn this paper we obtain several refinements of the Jensen inequality on time scales by generalizing Jensen’s functional for n-convex functions. We also investigate the bounds for the identities related to the new improvements obtained.
Common deficiencies found in generic Finished Pharmaceutical Product (FPP) applications submitted for registration to the South African Health Products Regulatory Authority (SAHPRA)
Authors: Moeti Lerato , Litedu Madira , Joubert Jacques 
Published: January 2022

Abstract
Background
The aim of the study was to investigate the common deficiencies observed in the Finished Pharmaceutical Product (FPP) section of generic product applications submitted to SAHPRA. The study was conducted retrospectively over a 7-year period (2011–2017) for products that were finalised by the Pharmaceutical and Analytical pre-registration Unit.

Methods
There were 3148 finalised products in 2011–2017, 667 of which were sterile while 2089 were non-sterile. In order to attain a representative sample for the study, statistical sampling was conducted. Sample size was obtained using the statistical tables found in literature and confirmed by a sample size calculation with a 95% confidence level. The selection of the products was according to the therapeutic category using the multi-stage sampling method called stratified-systematic sampling. This resulted in the selection of 325 applications for non-sterile products and 244 applications for sterile products. Subsequently, all the deficiencies were collected and categorised according to Common Technical Document (CTD) subsections of the FPP section (3.2.P).

Results
A total of 3253 deficiencies were collected from 325 non-sterile applications while 2742 deficiencies were collected from 244 sterile applications. The most common deficiencies in the FPP section for non-sterile products were on the following sections: Specifications (15%), Description and Composition (14%), Description of the Manufacturing Process (13%), Stability Data (7.6%) and the Container Closure System (7.3%). The deficiencies applicable to the sterile products were quantified and the subsection, Validation and/or Evaluation (18%) has the most deficiencies. Comparison of the deficiencies with those reported by other agencies such as the USFDA, EMA, TFDA and WHOPQTm are discussed with similarities outlined.

Conclusions
The overall top five most common deficiencies observed by SAHPRA were extensively discussed for the generic products. The findings provide an overview on the submissions and regulatory considerations for generic applications in South Africa, which is useful for FPP manufacturers in the compilation of their dossiers and will assist in accelerating the registration process.
Comparative analysis of proficiencies of various textures and geometric features in breast mass classification using k-nearest neighbor
Authors: Singh Harmandeep , Sharma Vipul , Singh Damanpreet 
Published: January 2022

AbstractThis paper introduces a comparative analysis of the proficiencies of various textures and geometric features in the diagnosis of breast masses on mammograms. An improved machine learning-based framework was developed for this study. The proposed system was tested using 106 full field digital mammography images from the INbreast dataset, containing a total of 115 breast mass lesions. The proficiencies of individual and various combinations of computed textures and geometric features were investigated by evaluating their contributions towards attaining higher classification accuracies. Four state-of-the-art filter-based feature selection algorithms (Relief-F, Pearson correlation coefficient, neighborhood component analysis, and term variance) were employed to select the top 20 most discriminative features. The Relief-F algorithm outperformed other feature selection algorithms in terms of classification results by reporting 85.2% accuracy, 82.0% sensitivity, and 88.0% specificity. A set of nine most discriminative features were then selected, out of the earlier mentioned 20 features obtained using Relief-F, as a result of further simulations. The classification performances of six state-of-the-art machine learning classifiers, namely k-nearest neighbor (k-NN), support vector machine, decision tree, Naive Bayes, random forest, and ensemble tree, were investigated, and the obtained results revealed that the best classification results (accuracy = 90.4%, sensitivity = 92.0%, specificity = 88.0%) were obtained for the k-NN classifier with the number of neighbors having k = 5 and squared inverse distance weight. The key findings include the identification of the nine most discriminative features, that is, FD26 (Fourier Descriptor), Euler number, solidity, mean, FD14, FD13, periodicity, skewness, and contrast out of a pool of 125 texture and geometric features. The proposed results revealed that the selected nine features can be used for the classification of breast masses in mammograms.
Implementation of clinical audit to improve adherence to guideline-recommended therapy in acute coronary syndrome
Authors: George Nimmy Elizabeth , Shukkoor Aashiq Ahamed , Joseph Noel , Palanimuthu Ramasamy , Kaliappan Tamilarasu , Gopalan Rajendiran 
Published: January 2022

Abstract
Background
Despite global consensus on the management of acute coronary syndrome (ACS), implementation of strategies to improve adherence of guideline-directed medical therapy (GDMT) remains sub-optimal, especially in developing countries. Thus, we aimed to assess the effect of clinical pharmacist-led clinical audit to improve the compliance of discharge prescriptions in patients admitted with ACS. It is a prospective clinical audit of ACS patients which was carried out for 12 months. The discharge prescriptions were audited by clinical pharmacists for the appropriateness in the usage of statins, dual antiplatelet therapy (DAPT), beta-blockers, and angiotensin-converting enzyme inhibitors (ACE-I)/angiotensin receptor blocker (ARB). A feedback report was presented every month to the cardiologists involved in the patient care, and the trend in the adherence to GDMT was analyzed over 12 months.

Results
The discharge prescriptions of 1072 ACS patients were audited for the justifiable and non-justifiable omissions of mandated drugs. The first-month audit revealed unreasonable omissions of DAPT, statin, ACE-I/ARB, and beta-blockers in 1%, 0%, 14%, and 11% respectively, which reduced to nil by the end of the 11th month of the audit–feedback program. This improvement remained unchanged until the end of the 12th month.

Conclusions
The study revealed that periodic clinical audit significantly improves adherence to GDMT in patients admitted with ACS.
Knowledge, attitudes, and practices of cardiopulmonary rehabilitation among physiotherapists in Lebanon
Authors: Farah Rebecca , Groot Wim , Pavlova Milena 
Published: January 2022

Abstract
Background
Insufficient physical activity is one of the leading mortality risks worldwide for cardiovascular and pulmonary diseases. Physiotherapists (PT) are core healthcare professionals who play a major role in the prevention of disease complications and in inspiring a healthy lifestyle. To identify challenges in the promotion of cardiopulmonary rehabilitation (CR) in Lebanon, a survey was conducted among PT and physiotherapy students. The aim was to assess the knowledge, attitudes, and practices of CR in Lebanon.

Results
The response rate was 46.1% (N = 322). Results show that 24.5% of respondents have good to excellent knowledge about CR. More than 60% of the respondents indicate possible barriers to starting a CR program, and one of two respondents identify the absence of skills as a main barrier. Findings highlight the importance of the role of PT as a mediator to increase a healthy lifestyle among patients and to promote the prevention of cardiovascular diseases and pulmonary diseases in the country.

Conclusions and recommendations
Our results support the evidence and clinical guidelines that PT play a major role by increasing the participation of patients in CR. A cost-effective CR program needs to be covered by the private and public system in Lebanon.