bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiac regeneration by direct reprogramming in this decade and beyond
Authors: Yamakawa Hiroyuki , Ieda Masaki 
Published: July 2021

AbstractJapan faces an increasing incidence of heart disease, owing to a shift towards a westernized lifestyle and an aging demographic. In cases where conventional interventions are not appropriate, regenerative medicine offers a promising therapeutic option. However, the use of stem cells has limitations, and therefore, “direct cardiac reprogramming” is emerging as an alternative treatment. Myocardial regeneration transdifferentiates cardiac fibroblasts into cardiomyocytes in situ.Three cardiogenic transcription factors: Gata4, Mef2c, and Tbx5 (GMT) can induce direct reprogramming of fibroblasts into induced cardiomyocytes (iCMs), in mice. However, in humans, additional factors, such as Mesp1 and Myocd, are required. Inflammation and immune responses hinder the reprogramming process in mice, and epigenetic modifiers such as TET1 are involved in direct cardiac reprogramming in humans. The three main approaches to improving reprogramming efficiency are (1) improving direct cardiac reprogramming factors, (2) improving cell culture conditions, and (3) regulating epigenetic factors. miR-133 is a potential candidate for the first approach. For the second approach, inhibitors of TGF-β and Wnt signals, Akt1 overexpression, Notch signaling pathway inhibitors, such as DAPT ((S)-tert-butyl 2-((S)-2-(2-(3,5-difluorophenyl) acetamido) propanamido)-2-phenylacetate), fibroblast growth factor (FGF)-2, FGF-10, and vascular endothelial growth factor (VEGF: FFV) can influence reprogramming. Reducing the expression of Bmi1, which regulates the mono-ubiquitination of histone H2A, alters histone modification, and subsequently the reprogramming efficiency, in the third approach. In addition, diclofenac, a non-steroidal anti-inflammatory drug, and high level of Mef2c overexpression could improve direct cardiac reprogramming.Direct cardiac reprogramming needs improvement if it is to be used in humans, and the molecular mechanisms involved remain largely elusive. Further advances in cardiac reprogramming research are needed to bring us closer to cardiac regenerative therapy.
Does city lockdown prevent the spread of COVID-19? New evidence from the synthetic control method
Authors: Yang Xiaoxuan 
Published: July 2021

AbstractBackgroundAt 10 a.m. on January 23, 2020 Wuhan, China imposed a 76-day travel lockdown on its 11 million residents in order to stop the spread of COVID-19. This lockdown represented the largest quarantine in the history of public health and provides us with an opportunity to critically examine the relationship between a city lockdown on human mobility and controlling the spread of a viral epidemic, in this case COVID-19. This study aims to assess the causal impact of the Wuhan lockdown on population movement and the increase of newly confirmed COVID-19 cases.MethodsBased on the daily panel data from 279 Chinese cities, our research is the first to apply the synthetic control approach to empirically analyze the causal relationship between the Wuhan lockdown of its population mobility and the progression of newly confirmed COVID-19 cases. By using a weighted average of available control cities to reproduce the counterfactual outcome trajectory that the treated city would have experienced in the absence of the lockdown, the synthetic control approach overcomes the sample selection bias and policy endogeneity problems that can arise from previous empirical methods in selecting control units.ResultsIn our example, the lockdown of Wuhan reduced mobility inflow by approximately 60 % and outflow by about 50 %. A significant reduction of new cases was observed within four days of the lockdown. The increase in new cases declined by around 50% during this period. However, the suppression effect became less discernible after this initial period of time. A 2.25-fold surge was found for the increase in new cases on the fifth day following the lockdown, after which it died down rapidly.ConclusionsOur study provided urgently needed and reliable causal evidence that city lockdown can be an effective short-term tool in containing and delaying the spread of a viral epidemic. Further, the city lockdown strategy can buy time during which countries can mobilize an effective response in order to better prepare. Therefore, in spite of initial widespread skepticism, lockdowns are likely to be added to the response toolkit used for any future pandemic outbreak.
Evaluation of cotton germplasm for morphological and biochemical host plant resistance traits against sucking insect pests complex
Authors: RIZWAN Muhammad , ABRO Saifullah , ASIF Muhammad Usman , HAMEED Amjad , MAHBOOB Wajid , DEHO Zaheer Ahmed , SIAL Mahboob Ali 
Published: July 2021

AbstractBackgroundSucking insect pests cause severe damage to cotton crop production. The development of insect resistant cotton cultivars is one of the most effective measures in curtailing the yield losses. Considering the role of morphological and biochemical host plant resistance (HPR) traits in plant defense, 12 cotton genotypes/varieties were evaluated for leaf area, leaf glanding, total soluble sugars, total soluble proteins, total phenolics, tannin and total flavonoids against fluctuating populations of whitefly, thrips and jassid under field conditions.ResultsThe population of these insects fluctuated during the growing season and remained above threshold level (whitefly > 5, thrips > (8–10), or jassid > 1 per leaf) during late June and early July. Strong and negative association of whitefly (r = − 0.825) and jassid (r = − 0.929) with seed cotton yield was observed. Mean population of insects were the highest in Glandless-1 followed by NIA-82 and NIA-M30. NIAB-Kiran followed by NIAB-878 and Sadori were the most resistant, with the mean population of 1.41, 1.60, 1.66 (whitefly); 2.24, 2.32, 2.53 (thrips) and 0.37, 0.31, 0.36 (jassid), respectively. The resistant variety NIAB-Kiran showed less soluble sugars (8.54 mg·g− 1), soluble proteins (27.11 mg·g− 1) and more phenolic (36.56 mg·g− 1) and flavonoids (13.10 mg·g− 1) as compared with the susceptible check Glandless-1. Moreover, all insect populations were positively correlated with total soluble sugars and proteins. Whitefly populations exhibited negative response to leaf gossypol glands, total phenolics, tannins and flavonoids. The thrips and jassid populations had a significant and negative correlation with these four biochemical HPR traits.ConclusionThe identified resistant resources and HPR traits can be deployed against sucking insect pests’ complex in future breeding programs of developing insect resistant cotton varieties.
VAECGAN: a generating framework for long-term prediction in multivariate time series
Authors: Yin Xiang , Han Yanni , Xu Zhen , Liu Jie 
Published: July 2021

AbstractLong-term prediction is still a difficult problem in data mining. People usually use various kinds of methods of Recurrent Neural Network to predict. However, with the increase of the prediction step, the accuracy of prediction decreases rapidly. In order to improve the accuracy of long-term prediction,we propose a framework Variational Auto-Encoder Conditional Generative Adversarial Network(VAECGAN). Our model is divided into three parts. The first part is the encoder net, which can encode the exogenous sequence into latent space vectors and fully save the information carried by the exogenous sequence. The second part is the generator net which is responsible for generating prediction data. In the third part, the discriminator net is used to classify and feedback, adjust data generation and improve prediction accuracy. Finally, extensive empirical studies tested with five real-world datasets (NASDAQ, SML, Energy, EEG,KDDCUP)demonstrate the effectiveness and robustness of our proposed approach.
Combined markers for predicting cognitive deficit in patients with Alzheimer’s disease
Authors: Hussen Dalia Farouk , Hussein Ayat Allah Farouk , Monzer Mahmoud Abdel Moety , Hammad Saida Ali 
Published: July 2021

Abstract
Background
Alzheimer’s disease (AD) is the most widely recognized type of dementia. It is associated with cell cycle abnormalities including genomic instability and increased micronuclei (MNi) which usually evolve many years before the appearance of the clinical manifestations. Digital electroencephalogram (EEG) has a role in perceiving brain changes in dementia and in early detection of cognitive decline. This study aimed to assess the competency of using neurophysiological markers including absolute power of alpha waves and a cytogenetic marker which comprises scoring of MNi as a step toward early and preclinical diagnosis of AD. The study was conducted on 27 subjects; they were 15 patients diagnosed as sporadic AD and a group of 12 age and sex-matched controls. All subjects were subjected to Mini-Mental State Examination (MMSE), conventional EEG, digital EEG, and cytokinesis-block micronucleus assay (CBMN) in peripheral blood lymphocytes.

Results
Conventional EEG showed a normal background activity with no abnormal epileptogenic discharges in both groups. Digital EEG showed significant reduction of the absolute power of alpha waves for AD patients as compared to the control group (P < 0.0001). Score of MNi showed statistical significant difference between the two groups (P < 0.0001). By linking scores of both cognitive state using MMSE and MNi among the group of patients, a significant negative correlation was detected (r = −0.6066). The correlations between cognitive state and the absolute power of alpha wave among the patients revealed a positive correlation (r = 0.2235).

Conclusions
The combination of both cytogenetic and neurophysiological markers can be beneficial for early detection of cognitive decline and may lead to preclinical identification of individuals at increased risk for AD, where at this stage treatment is constructive. The negative correlation between the scores of MNi and MMSE is suggestive for the impact of genomic instability on the cognitive state.
A descriptive study of agoraphobic situations and correlates on panic disorder
Authors: Barzegar Habibeh , Farahbakhsh Mostafa , Azizi Hosein , Aliashrafi Sepideh , Dadashzadeh Hossein , Fakhari Ali 
Published: July 2021

Abstract
Background
We aimed to identify the distribution and effective factors of agoraphobic situations and how they relate to panic disorder. We included confirmed 61 patients with agoraphobia in Bozorgmehr Psychiatric Clinic of Tabriz. Multiple logistic regression was used to measure panic disorder, agoraphobia, and effective factors.

Results
The average age of participants was 37.26 (SD 10.9), including 68.85% female and 31.15% male. Out of those, around three-fourths, 45 (73.7%), had panic disorder or comorbidity at least by one psychiatric disorder. Among various types of agoraphobia situations, leaving 34.63% and being 32.63% home alone had the most occurrences. A trend was observed between the rising of agoraphobia situations and panic risk. The final analysis was found a significant relationship between being bathroom alone (OR = 1.3; CI 1.12–1.56), having more than one psychiatric disorder (AOR = 8.25; CI 1.12–27.17), and panic risk.

Conclusions
We found leaving home alone, being home alone, being in a crowd, and standing in line as the most common agoraphobic situations. There appears agoraphobia and panic disorders are poorly understood in primary mental health care systems. The screening and treating programs are needed for increasing the quality of life and early identification of these disorders.
Anti-angiogenesis in cancer therapeutics: the magic bullet
Authors: Oguntade Ayodipupo S. , Al-Amodi Faez , Alrumayh Abdullah , Alobaida Muath , Bwalya Mwango 
Published: July 2021

Abstract
Background
Angiogenesis is the formation of new vascular networks from preexisting ones through the migration and proliferation of differentiated endothelial cells. Available evidence suggests that while antiangiogenic therapy could inhibit tumour growth, the response to these agents is not sustained. The aim of this paper was to review the evidence for anti-angiogenic therapy in cancer therapeutics and the mechanisms and management of tumour resistance to antiangiogenic agents. We also explored the latest advances and challenges in this field.

Main body of the abstract
MEDLINE and EMBASE databases were searched for publications on antiangiogenic therapy in cancer therapeutics from 1990 to 2020. Vascular endothelial growth factor (VEGF) is the master effector of the angiogenic response in cancers. Anti-angiogenic agents targeting the VEGF and HIF-α pathways include monoclonal antibodies to VEGF (e.g. bevacizumab), small-molecule tyrosine kinase inhibitors (TKIs) e.g. sorafenib, decoy receptor or VEGF trap e.g. aflibercept and VEGFR2 inhibitors (e.g. ramucirumab). These classes of drugs are vascular targeting which in many ways are advantageous over tumour cell targeting drugs. Their use leads to a reduction in the tumour blood supply and growth of the tumour blood vessels. Tumour resistance and cardiovascular toxicity are important challenges which limit the efficacy and long-term use of anti-angiogenic agents in cancer therapeutics. Tumour resistance can be overcome by dual anti-angiogenic therapy or combination with conventional chemotherapy and immunotherapy. Emerging nanoparticle-based therapy which can silence the expression of HIF-α gene expression by antisense oligonucleotides or miRNAs has been developed. Effective delivery platforms are required for such therapy.

Short conclusion
Clinical surveillance is important for the early detection of tumour resistance and treatment failure using reliable biomarkers. It is hoped that the recent interest in mesenchymal cell-based and exosome-based nanoparticle delivery platforms will improve the cellular delivery of newer anti-angiogenics in cancer therapeutics.
Does gender diversity on firm’s board affect dividend payouts? Evidence from India
Authors: Mulchandani Kalyani , Mulchandani Ketan , Jasrotia Sahil Singh 
Published: July 2021

AbstractThis study attempts to determine whether gender diversity on the firm's board affects the dividend payout ratio concerning firms listed on Nifty 50 in India. Multiple regression analysis and the logit model have been employed. The dependent variable is the dividend payout policy of the firm, and the independent variable is gender diversity. The regression model incorporated control variables that have been popularly listed in the extant literature. The robustness of the results has also been tested. It was found that there exists a positive association between the percentage of female directors and the dividend payout ratio. Results also found that there is a positive impact of the number of female directors on the dividend to total assets. This implies that gender diversity on board positively affects the payout ratio of firms. This study is the first of its kind to investigate the association of gender diversity on the firm's board and dividend payout ratio.
Probiotic therapy in patients with irritable bowel syndrome: does it have a real role?
Authors: Fawzy Iman Mohamed , ElGindy Eman Mohamed , Abdel-Samie Omar , Aly Heba 
Published: July 2021

Abstract
Background
Irritable bowel syndrome (IBS) is one of the most prevalent functional gastrointestinal disorders (FGIDs). There is good evidence that microbiota plays a predominant role in the IBS pathophysiology. The aim of the study is to evaluate the role of probiotics in improvement of IBS symptoms via IBS-symptom severity scale (IBS-SSS Arabic version) and improvement of quality of life via irritable bowel syndrome-quality of life survey (IBS-QOL).

Results
This double-armed comparative trial was conducted on IBS patients, who fulfill ROME IV criteria and the IBS diagnostic questionnaire between August and December 2019. Ninety patients were followed up for 4 weeks from the first visit. The first group was prescribed probiotics (10 billion colony of Lactobacillus delbruekii and Lactobacillus fermentum) and itopride hcl 50 mg three times daily, while the second group received only itopride hcl 50 mg by the same dose for 4 weeks. There was a highly significant improvement in the IBS-SSS score in group 1 after 4 weeks of treatment than in group 2 (137.56±67.53 vs 258.44±34.18) (p=0.001). Also, there was a highly significant improvement in the overall QOL terms in group 1 in comparison with baseline QOL score [with overall mean score (60.64±7.77) at baseline vs (81.54±7.87) at 4 weeks (p value <0.001)].

Conclusion
Probiotics are useful for the improvement of IBS symptoms and quality of life of the studied patients. Larger multicenter studies are needed in the future.
Natural Language Processing for Patient Selection in Phase I or II Oncology Clinical Trials
Authors: Delorme Julie , Charvet Valentin , Wartelle Muriel , Lion François , Thuillier Bruno , Mercier Sandrine , Soria Jean-Charles , Azoulay Mikael , Besse Benjamin , Massard Christophe , Hollebecque Antoine , Verlingue Loic 
Published: July 2021

PURPOSE Early discontinuation affects more than one third of patients enrolled in early-phase oncology clinical trials. Early discontinuation is deleterious both for the patient and for the study, by inflating its duration and associated costs. We aimed at predicting the successful screening and dose-limiting toxicity period completion (SSD) from automatic analysis of consultation reports. MATERIALS AND METHODS We retrieved the consultation reports of patients included in phase I and/or phase II oncology trials for any tumor type at Gustave Roussy, France. We designed a preprocessing pipeline that transformed free text into numerical vectors and gathered them into semantic clusters. These document-based semantic vectors were then fed into a machine learning model that we trained to output a binary prediction of SSD status. RESULTS Between September 2012 and July 2020, 56,924 consultation reports were used to build the dictionary and 1,858 phase I or II inclusion reports were used to train (72%), validate (14%), and test (14%) a random forest model. Preprocessing could efficiently cluster words with semantic proximity. On the unseen test cohort of 264 consultation reports, the performances of the model reached: F1 score 0.80, recall 0.81, and area under the curve 0.88. Using this model, we could have reduced the screen fail rate (including dose-limiting toxicity period) from 39.8% to 12.8% (relative risk, 0.322; 95% CI, 0.209 to 0.498; P < .0001) within the test cohort. Most important semantic clusters for predictions comprised words related to hematologic malignancies, anatomopathologic features, and laboratory and imaging interpretation. CONCLUSION Machine learning with semantic conservation is a promising tool to assist physicians in selecting patients prone to achieve SSD in early-phase oncology clinical trials.
Solid-in-Oil-in-Water Emulsion: An Innovative Paradigm to Improve Drug Stability and Biological Activity
Authors: Sawant Anali , Kamath Seema , KG Hemanth , Kulyadi Girish Pai 
Published: July 2021

Abstract
An emulsion is a biphasic dosage form comprising of dispersed phase containing droplets that are uniformly distributed into a surrounding liquid which forms the continuous phase. An emulsifier is added at the interface of two immiscible liquids to stabilize the thermodynamically unstable emulsion. Various types of emulsions such as water-in-oil (w-o), oil-in-water (o-w), microemulsions, and multiple emulsions are used for delivering certain drugs in the body. Water (aqueous) phase is commonly used for encapsulating proteins and several other drugs in water-in-oil-in-water (w-o-w) emulsion technique. But this method has posed certain problems such as decreased stability, burst release, and low entrapment efficiency. Thus, a novel “solid-in-oil-in-water” (s-o-w) emulsion system was developed for formulating certain drugs, probiotics, proteins, antibodies, and tannins to overcome these issues. In this method, the active ingredient is encapsulated as a solid and added to an oil phase, which formed a solid-oil dispersion. This dispersion was then mixed with water to form a continuous phase for enhancing the drug absorption. This article focuses on the various studies done to investigate the effectiveness of formulations prepared as solid-oil-water emulsions in comparison to conventional water-oil-water emulsions. A summary of the results obtained in each study is presented in this article. The s-o-w emulsion technique may become beneficial in near future as it has shown to improve the stability and efficacy of the entrapped active ingredient.

Graphical abstract
Modulation of mitochondrial nucleoid structure during aging and by mtDNA content in Drosophila
Authors: Wang Li-jie , Hsu Tian , Lin Hsiang-ling , Fu Chi-yu 
Published: July 2021

ABSTRACT
Mitochondrial DNA (mtDNA) encodes gene products that are essential for oxidative phosphorylation. They organize as higher order nucleoid structures (mtNucleoids) that were shown to be critical for the maintenance of mtDNA stability and integrity. While mtNucleoid structures are associated with cellular health, how they change in situ under physiological maturation and aging requires further investigation. In this study, we investigated the mtNucleoid assembly at an ultrastructural level in situ using the TFAM-Apex2 Drosophila model. We found that smaller and more compact TFAM-nucleoids are populated in the mitochondria of indirect flight muscle of aged flies. Furthermore, mtDNA transcription and replication were cross-regulated in the mtTFB2-knockdown flies as in the mtRNAPol-knockdown flies that resulted in reductions in mtDNA copy numbers and nucleoid-associated TFAM. Overall, our study reveals that the modulation of TFAM-nucleoid structure under physiological aging, which is critically regulated by mtDNA content.
Early perturbation of Wnt signaling reveals patterning and invagination-evagination control points in molar tooth development
Authors: Kim Rebecca , Yu Tingsheng , Li Jingjing , Prochazka Jan , Sharir Amnon , Green Jeremy B. A. , Klein Ophir D. 
Published: July 2021

ABSTRACT
Tooth formation requires complex signaling interactions both within the oral epithelium and between the epithelium and the underlying mesenchyme. Previous studies of the Wnt/β-catenin pathway have shown that tooth formation is partly inhibited in loss-of-function mutants, and gain-of-function mutants have perturbed tooth morphology. However, the stage at which Wnt signaling is first important in tooth formation remains unclear. Here, using an Fgf8-promoter-driven, and therefore early, deletion of β-catenin in mouse molar epithelium, we found that loss of Wnt/β-catenin signaling completely deletes the molar tooth, demonstrating that this pathway is central to the earliest stages of tooth formation. Early expression of a dominant-active β-catenin protein also perturbs tooth formation, producing a large domed evagination at early stages and supernumerary teeth later on. The early evaginations are associated with premature mesenchymal condensation marker, and are reduced by inhibition of condensation-associated collagen synthesis. We propose that invagination versus evagination morphogenesis is regulated by the relative timing of epithelial versus mesenchymal cell convergence regulated by canonical Wnt signaling. Together, these studies reveal new aspects of Wnt/β-catenin signaling in tooth formation and in epithelial morphogenesis more broadly.