bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide inference reveals that feedback regulations constrain promoter-dependent transcriptional burst kinetics
Authors: zhou tianshou 
Published: April 2022

Abstract

Background: A major challenge in transcriptional regulation is to understand how static promoter architecture and dynamic feedback regulation dictate transcriptional burst kinetics on a genome-wide scale. Although single-cell RNA sequencing (scRNA-seq) provides an opportunity to address this issue, analytical methods need to be developed to uncover molecular mechanisms governing burst kinetics.Results: We develop an interpretable and scalable statistical framework, which combines experimental data with a mechanistic model to infer transcriptional burst kinetics (sizes and frequencies) and feedback regulations. Applying this framework to the scRNA-seq data of embryonic mouse fibroblast cells, we find that genome-wide burst kinetics exhibit different characteristics in cases without and with feedback regulations, implying Simpson’s paradoxes. We show that feedbacks modulate burst frequencies and sizes differently and conceal the effects of transcription start site distributions on burst kinetics. Notably, only in the presence of positive feedback, TATA genes are expressed with high burst frequencies, and enhancer-promoter interactions mainly modulate burst frequencies.Conclusions: The inference method developed here provides a flexible, robust, and efficient way to infer molecular mechanisms dictating burst kinetics. Our study reveals genome-wide burst patterns coordinated by promoter architecture and feedback regulations.
Footwear, foot orthoses and strengthening exercises for the non-surgical management of hallux valgus: protocol for a randomised pilot and feasibility trial
Authors: Menz Hylton , Lim Polly Q , Hurn Sheree E , Mickle Karen J , Buldt Andrew K , Cotchett Matthew P , Roddy Edward , Wluka Anita E , Erbas Bircan , Munteanu Shannon E 
Published: April 2022

Abstract
Background
Hallux valgus is a common and disabling condition. This randomised pilot and feasibility trial aims to determine the feasibility of conducting a fully-powered parallel group randomised trial to evaluate the effectiveness of a multifaceted non-surgical intervention for reducing pain associated with hallux valgus.
Methods
Twenty-eight community-dwelling women with painful hallux valgus will be randomised to receive either a multifaceted, non-surgical intervention (footwear, foot orthoses, foot exercises, advice, and self-management) or usual care (advice and self-management alone). Outcome measures will be obtained at baseline, 4, 8 and 12 weeks. The primary outcome is feasibility, which will be evaluated according to demand, acceptability, adherence, adverse events, and retention rate. Limited efficacy testing will be conducted on secondary outcome measures including foot pain (the Manchester-Oxford Foot Questionnaire), foot muscle strength (hand-held dynamometry), general health-related quality of life (the Short Form-12), use of cointerventions, and participants’ perception of overall treatment effect. Biomechanical testing will be conducted at baseline to evaluate the immediate effects of the footwear/orthotic intervention on pressure beneath the foot and on the medial aspect of the first metatarsophalangeal joint and hallux.
Discussion
This study will determine the feasibility of conducting a fully-powered randomised trial of footwear, foot orthoses, foot exercises, advice and self-management for relieving pain associated with hallux valgus and provide insights into potential mechanisms of effectiveness.
Socio-Economic Characterization of Community in Watershed Management: Case of Abaya- Chamo Sub-Basin Project Districts of Southern Ethiopia.
Authors: Mamo Abebe Asele 
Published: April 2022

Abstract
Background
Watershed management is being recognized as a suitable alternative intervention in managing natural resources. Characterizations of watershed management project in terms of socio-economic baseline study helps to evaluate whether a change making a difference. It is used during the project to indicate progress toward the objectives, and after the project to measure the amount of the change. This study aimed at baseline characterization with special reference to socio-economic aspects to suggest appropriate policy directions for enhancing watersheds programs towards achieving integrated Water Resource Management. The study area was in the Abaya-Chamo sub-basin of Rift Valley Lakes Basin of southern Ethiopia. To record benchmarks of socio-economic characteristics, the study was carried out in Amaro, Chencha, Humbo, Lokabaya, Mirababaya, Arbaminch city administration, and Abaya districts covering 7 Kebeles and 7 villages that were accessible for data collection.
Results
The major objective of the study was a socio-economic characterization of community in watershed management programs in seven watershed management districts of the Abaya-Chamo sub-basin of southern Ethiopia. The study was carried out using secondary raw data collected by Rift Valley Lakes Basin Authority (RVLBA). StataMP 13 and MS Excel were used for the analysis of the data. The major income sources of the farmers in the study area were crop production, animal husbandry, and tree land. Lack of educational institutions, poor economic conditions, and lack of access to the far located institutions was observed to be the conspicuous reason for the low literacy rate in the study area. Typhoid, typhus, Mosquitoes, Diarrhea, tuberculosis, and other water-borne disease were the major disease found in the study area.
Conclusions
Demographic characteristics, Income status, and social status were the major components of the socio-economy focused in this study. Agriculture in the area is the major source of income basically of a subsistence nature - characterized by low input – low output. Therefore, socio-economic improvement depends upon resource mapping very crucial for planning appropriate intervention. Access to education should be improved and children's attendance at school should be encouraged and facilitated.
ANÁLISE DA ASSISTÊNCIA À SAÚDE DA MULHER NOS MUNICÍPIOS DE PEQUENO PORTE DA REGIONAL DE SAÚDE DE BELO HORIZONTE
Authors: Costa Luciana , Bezerra Ana Paula , Oliveira Fernanda , Campos Kátia 
Published: April 2022

RESUMO
Objetivo: Esse trabalho faz parte de um recorte do projeto de pesquisa “A gestão do Sistema Único de Saúde: um estudo nos municípios de pequeno porte da Regional de Saúde de Belo Horizonte” que tem o objetivo de analisar os indicadores propostos pelo pacto interfederativo 2017-2021 que mensuram fatores associados à saúde da mulher, incluindo gestante e puérpera. Fundamentação teórica: A adesão à programas que visam ações para adequar e ampliar o cuidado da atenção à saúde da mulher é essencial. Método: análise descritiva a partir de dados secundários de sistemas de informações em saúde tendo como foco oito municípios de pequeno porte da Regional de Saúde de Belo Horizonte. Resultados: Os resultados mostraram que houve alguns avanços, mas ainda há fatores que devem ser estruturados para promover uma assistência de qualidade à saúde da mulher. Conclusão: Há necessidade de investir na melhoria de acesso e a melhor organização da Atenção Primária para assistência ao pré-natal e parto.
“Umzi ka mama Rhodes University PhD research project,” February 23, 2021, produced by Phemelo Hellemann and Thingo Mthombeni, methodology video, 16:51.
Authors: Hellemann Phemelo 
Published: April 2022

<p>This African feminist study enlists narratives of a sample of seven African female heads of households residing in Fingo Village who are also property owners. Fingo Village is an atypical environment where African people had a rare legal advantage of owning title deeds dating back to 1855.</p>
<p><br></p>
<p>The first phase of the research involved engaging with the literature about the title deeds history of Fingo Village and conducting oral history interviews that served as data. In the second phase, the interviews were analysed and packaged in a documentary format. The third phase was a playback theatre inspired session in a 10-minute performance based on themes from the participants’ filmed interviews. </p>
<p><br></p>
<p>Additionally, the performance was a catalyst for forum theatre activities that allowed the participants to interact with the performer and suggest solutions to the dilemma posed by the performer regarding family property use. The participants were decision-makers and family property relations experts within this imagined context. In the fourth phase, the image theatre adaptation and memory work activities were essential tools. The tools aided the visuals and information from an existing Fingo Village exhibition as additional resources that prompted dialogue and discussions. The exhibition encouraged participants to share their personal experiences and memories of the Group Areas Act (GAA) era.</p>
<p><br></p>
<p>The findings showed that the GAA era saw many families revert to communal tenure practices as a strategy to evade forced sales; as such, this gave rise to undocumented family property transfers. Additionally, the findings revealed that though customary practices are often patriarchal, there are circumstances favouring women as the preferred family property custodian. These are embedded in the social status of women who are traditional healers, firstborn daughters, and those from families with just daughters.</p>
<p><br></p>
<p>This study contributes to the growing literature that advocates for positive representation of African women’s stories by using active research methodologies that strengthen partnerships and shared authority between the researcher and the public. This methodology could inspire other researchers to explore theatre techniques to create more profound and meaningful engagements with their participants.</p>
In Silico Optimization of Frizzled-8 Receptor Inhibition Activity of Carbamazepine: Designing New Anti-Cancer Agent
Authors: Sepehri Bakhtyar , Ghavami Raouf , Ahmadi Roya , Irani Mehdi 
Published: April 2022

Background:Frizzled-8 (FZD8) receptor is a therapeutic target for cancer treatment and recent research has shown that carbamazepine (CBZ) can inhibit this receptor.Objective:In this work, it has been tried to optimize CBZ to enhance its binding capacity to the N6W binding site of FZD8 by using structure-based drug design methods.Methods:CBZ and its 83 derivatives were docked to the N6W binding site of FZD8.Results:Docking results show that two compounds 79 and 82 have the smallest binding energies and are fitted to the N6W binding site. Compounds C79 and C82 have been synthesized by replacing a hydrogen atom of the seven-membered ring in CBZ with benzoate and nicotinate groups, respectively. In addition, docking results show that a trifluoromethyl on one of the phenyl rings is favorable for improving the FZD8 inhibition activity of the molecule.Conclusion:Both molecules C79 and C82 were subjected to molecular dynamics (MD) simulation. MD results show that FZD8-C82 complex is stable and this compound binds to the N6W binding site more strongly than compounds C79 and CBZ.
New Insights of Early Brain Injury after Subarachnoid Hemorrhage: A
Focus on the Caspase Family
Authors: Wang Xiaoyu , Xu Penglei , Liu Yibo , Wang Zefeng , Lenahan Cameron , Fang Yuanjian , Lu Jianan , Zheng Jingwei , Wang Kaikai , Wang Wei , Zhou Jingyi , Chen Sheng , Zhang Jianming 
Published: April 2022

Abstract:
Spontaneous subarachnoid hemorrhage (SAH), primarily caused by ruptured intracranial
aneurysms, remains a prominent clinical challenge with a high rate of mortality and morbidity
worldwide. Accumulating clinical trials aiming at the prevention of cerebral vasospasm (CVS) have
failed to improve the clinical outcome of patients with SAH. Therefore, a growing number of studies
have shifted focus to the pathophysiological changes that occur during the periods of early brain
injury (EBI). New pharmacological agents aiming to alleviate EBI have become a promising direction
to improve outcomes after SAH. Caspases belong to a family of cysteine proteases with diverse
functions involved in maintaining metabolism, autophagy, tissue differentiation, regeneration, and
neural development. Increasing evidence shows that caspases play a critical role in brain pathology
after SAH. Therefore, caspase regulation could be a potential target for SAH treatment. Herein, we
provide an overview pertaining to the current knowledge on the role of caspases in EBI after SAH,
and we discuss the promising therapeutic value of caspase-related agents after SAH.
Insights into the Cellular Interactions and Molecular Mechanisms of Ketogenic Diet for Comprehensive Management of Epilepsy
Authors: Singh Damanpreet , Kumar Amit , Kumari Savita 
Published: April 2022

Abstract:A high-fat diet with appropriate protein and low carbohydrate content, widely known as the ketogenic diet (KD), is considered as an effective non-pharmacotherapeutic treatment option for certain types of epilepsies. Several preclinical and clinical studies have been carried out to elucidate its mechanism of antiepileptic action. Ketone bodies produced after KD's breakdown interact with cellular excito-inhibitory processes and inhibit abnormal neuronal firing. The generated ketone bodies decrease glutamate release by inhibiting the vesicular glutamate transporter 1 and alter the transmembrane potential by hyperpolarization. Apart from their effect on the well-known pathogenic mechanisms of epilepsy, some recent studies have shown the interaction of KD metabolites with novel neuronal targets, particularly adenosine receptors, adenosine triphosphate-sensitive potassium channel, mammalian target of rapamycin, histone deacetylase, hydroxycarboxylic acid receptors, and the NLR family pyrin domain containing 3 inflammasomes to suppress seizures. The role of KD in augmenting gut microbiota as a potential mechanism for epileptic seizure suppression has been established. Furthermore, some recent findings also support the beneficial effect of KD against epilepsy- associated comorbidities. Despite several advantages of the KD in epilepsy management, its use is also associated with a wide range of side effects. Hypoglycemia, excessive ketosis, acidosis, renal stones, cardiomyopathies, and other metabolic disturbances are the primary adverse effects observed with the use of KD. However, in some recent studies, modified KD has been tested with lesser side effects and better tolerability. The present review discusses the molecular mechanism of KD and its role in managing epilepsy and its associated comorbidities.
A Machine Learning Language to Build a QSAR Model of Pyrazoline Derivative Inhibitors Targeting Mycobacterium tuberculosis Strain H37Rv
Authors: Thangavelu Prabha , Venkatesan Jayaprakash , Jubie Selvaraj , Jayapalan Sudeepan , Sivakumar Thangavel 
Published: April 2022

Background:Machine learning has become an essential tool for drug research to generate pertinent structural information to design drugs with higher biological activities. Quantitative structureactivity relationship (QSAR) is considered one technique. QSAR study involves two main steps: first is the generation of descriptors, and the second is building and validating the models.Aim:By using a Python program language for building the QSAR model of pyrazoline derivatives, the data were collected from diverse literature for the inhibition of Mycobacterium tuberculosis. Pyrazoline, a small molecule scaffold, could block the biosynthesis of mycolic acids, resulting in mycobacteria death and leading to anti-tubercular drug discovery.Methods:We have developed a new Python script that effectively uses CDK descriptor as the independent variable and anti-tubercular bioactivity as the dependent variable in building and validating the best QSAR model. The built QSAR model was further cross-validated by using the external test set compounds. Then, the three algorithms, viz. multiple linear regression, support vector machine, and partial least square classifiers, were used to differentiate and compare their r2 values.Results:Our generated QSAR model via an open-source python program predicted well with external test set compounds. The generated statistical model afforded the ordinary least squares (OLS) regression as R2 value of 0.514, F value of 5.083, the adjusted R2 value of 0.413, and std. error of 0.092. Moreover, the multiple linear regression showed the R2 value of 0.5143, reg.coef_ of, -0.07795 (PC1), 0.01619 (PC2), 0.03763 (PC3), 0.07849 (PC4), -0.09726 (PC5), and reg.intercept_ of 4.8324. The performance of the model was determined by the support vector machine classifier of sklearn, module and it provided a model score of 0.5901. Further, the model performance was supported by a partial least square regression, and it showed the R2 value of 0.5901. The model performance was validated, and the model predicted similar values when compared to that of the train set, and the plotted linear curve between the predicted and actual pMIC50 value showed all data to fall over the middle linear line.Conclusion:We have found that the model score obtained using this script via three diverse algorithms correlated well, and there was not much difference between them; the model may be useful in the design of a similar group of pyrazoline analogs as anti-tubercular agents.
An Insight into the Recent Synthetic Approaches of Benzimidazole Motifs
Based on Divergent Substrate Scope
Authors: Kavya G. , Nair Ajil R. , Sivan Akhil 
Published: April 2022

Abstract:
Simple heterocyclic moieties are quite famous in synthetic organic chemistry due to their bioavailability, ease of laboratory synthesis, and variety of applications in multidisciplinary fields. Benzimidazole is an N-containing benzofused chemical compound with the formula C7H6N2 and belongs to the family of heterocyclic aromatic organic compounds. It is a potent bioactive molecule with prominent therapeutic activities and found to have prior importance in medicinal chemistry. Several advanced investigations in this area also proved that benzimidazole and its derivatives have significant antimicrobial, antiparasitic, antifungal, and anti-carcinogenic activities. It has also gained popularity in material science as well. Because of its versatile applications, numerous research groups paid considerable attention towards the synthesis of benzimidazoles. o-Phenylenediamine (OPD) is considered as the traditional substrate for benzimidazole synthesis. In this review, we discussed the synthetic approaches of benzimidazoles from OPD as a primary reactant with diverse substrates like aldehydes, alcohols, carboxylic acids/esters, etc. We have also briefed up reactions which uses the primary substrates such as o-nitroanilines and o-dinitro benzenes. This review report covers research findings which are published from 2016 till date and describes numerous practical and greener methods of synthesis. It also narrates innovative biocatalysts, photocatalysts and nano-catalysts, which are used for the synthesis of benzimidazoles.
Attenuation of Free Radicals and Exhibition of Antibacterial Activity by
Traditionally used Volatile Oils
Authors: Mishra Arun Kumar , Asif Mohd. , Sagar Anesh , Singh Harpreet , Mishra Amrita 
Published: April 2022

Background:
This study aimed to isolate and analyse the essential oils of Eugenia caryophyllus
flower buds and Citrus reticulata peels for antioxidant and antibacterial properties.

Methods:
By using the DPPH (2,2-diphenyl-1-picryl-hydrazyl-hydrate) free radical method and
the ferric reducing antioxidant power (FRAP) method, the antioxidant activities of total volatile oil
components of both oils were assessed. Agar well diffusion and dilution were used to test antibacterial
activity.

Results:
Optical rotation (0.95 and 1.01), weight per mL (1.03 and 1.06), and refractive index
(1.52 and 1.53) were all tested for both oils. The existence of a total of 26 and 28 most important
volatile chemical components in oils produced from Eugenia caryophyllus and Citrus reticulata,
respectively, was determined by GC-MS chemical analysis of the total volatile component. Retention
time in a Gas Chromatography (GC) technique was used to identify the components. The mass
spectral database was used to identify the values of oil components. The predominant components
were eugenol (77.08%) in Eugenia caryophyllus oil and limonene (78.46%) in Citrus reticulate oil.
Eugenia caryophyllus oil has strong antibacterial action against microorganisms like S. pyrogenes,
with a ZOI of 15.90–26.84 mm, followed by oil from Citrus reticulata peels with a ZOI of 14.60-
22.82 mm.

Conclusion:
The presence of terpenes and phenolics in both essential oils resulted in substantial
antioxidant activity. Agar well diffusion and dilution were used to test antibacterial activity. In the
concentration range of 5–100 mg/mL, both essential oils demonstrated good bacteriostatic and
bactericidal activity against microbial strains.
Formulation Development and Optimization of Blonanserin Liquid
SMEDDS using D-Optimal Mixture Design
Authors: Vaghela Sohansinh , Chaudhary Sunita , Chaudhary Ankit 
Published: April 2022

Background:
Blonanserin is an atypical antipsychotic potent antagonist of dopamine-D2
and D3 receptors with low aqueous solubility BCS class II drugs.

Objective:
The present research aims to develop and optimize the Blonanserin-loaded liquid selfmicro
emulsifying drug delivery system (SMEDDS) to improve its in vitro drug release by D-optimal
mixture design.

Methods:
Saturation solubility of Blonanserin was checked in various oils, surfactants, and cosurfactants.
The pseudo-ternary phase diagram was developed to identify the region of the microemulsion.
Trial batches were designed to determine dependent and independent variables in the formulation. DOptimal
Mixture design applies for optimization and minimized trials. The amount of oil(X1), surfactant(
X2), and co-surfactant(X3) were selected as independent variables, and solubility(Y1) and in vitro
percentage cumulative drug release(Y2) and size of globule(Y3) after 250 times dilution were selected
as the dependant variable. The level of the independent variables in the design will be selected based
on the drug's phase diagram, trial batches, and solubility. The developed SMEDDS was then evaluated
for globule size, transparency, self-emulsification time, in vitro dissolution, and relative dissolution of
the final formulation with marketed products and a pure drug.

Results:
BLN shows the highest solubility in (1:1) Captex 200P: Capmul MCM (oil), Tween 20 (surfactant),
and Ethanol (cosurfactant). Trial batches were shown at 1:9, 2:8, and 3:7 oil to surfactant and
cosurfactant ratios suitable for optimization. Optimization using a D-optimal mixture design gives 11
run batches and the resulting surface and contour plot suggest the best design space. The optimized
formula given by the mixture design of the target formulation had maximum drug solubility, maximum
drug release, and minimum globule size. Optimized formula containing Blonanserin, Captex
200P: Capmul MCM (1:1) Mixture (23% v/v), Tween 80 (57% v/v), and Ethanol (20% v/v) having
94.72% in vitro diffusion within 30 min with 21 nm globule size. Optimized liquid SMEDDS have a
higher in-vitro diffusion rate than marketed products and pure drugs.

Conclusion:
Blonanserin liquid SMEDDS was successfully developed with high solubility, nanoglobule
size, and improvement in in-vitro diffusion rate and vice versa for improvement in bioavailability
of the drug.