bluuebunny/crossref_metadata_2025_split huggingface dataset:
Osteoporosis and Stroke: A Bidirectional Mendelian Randomization Study
Authors: He Miao , Yong Haochuan , Li Jie 
Published: August 2024

Abstract

Objective: Numerous observational studies have identified a link between osteoporosis and stroke. However, the causal genetic relationship between these conditions remains unclear. This study employs a two-sample bidirectional Mendelian randomization (MR) approach to ascertain the causal relationship between osteoporosis and stroke.
Design: We conducted a two-sample Mendelian randomization (MR) study to investigate the potential causal relationship between osteoporosis and stroke, including its subtypes. Genetic data for osteoporosis and stroke, along with their subtypes, were sourced from published genome-wide association studies (GWAS). Single nucleotide polymorphisms (SNPs) demonstrating genome-wide significance (p < 5×10^−8) and independence (r^2 < 0.001) were selected for further analysis, provided they had an F-statistic ≥10. The inverse-variance weighted (IVW) method was employed to evaluate causality, with results reported as odds ratios (ORs). Heterogeneity was assessed using Cochran’s Q test, while pleiotropy was tested using the MR-Egger intercept test. A leave-one-out sensitivity analysis was performed to ensure the robustness of the results.
Results: Employing the IVW method, MR Egger method, and median-weighted method, we found no significant bidirectional causal relationship between osteoporosis and stroke or its subtypes, irrespective of the inclusion of potential pleiotropic SNPs. Sensitivity analyses affirmed the reliability and stability of these findings.
Conclusion: This study indicates that there is no bidirectional causal relationship between osteoporosis and stroke or its subtypes. Nevertheless, these conditions share similar pathophysiological mechanisms and pathways.
Cannabidiol Interactions with Outer Membrane Proteins in Salmonella Typhimurium LT2
Authors: Ibrahim Iddrisu , Ndezure Emmanuel , Xu Junhuan , Boakai Robertson K. , Ajayi Olufemi S. , Ayariga Joseph Atia 
Published: August 2024

Abstract

Cannabidiol (CBD), the non-psychoactive component of the hemp plant has tremendous potential as a novel antimicrobial agent. This study aimed at understanding the interactions between CBD and the outer membrane proteins (OMPs) of Salmonella Typhimurium LT2. Employing in silico techniques, we analyzed the binding affinities, interaction dynamics, and drug-likeness of CBD with key OMPs such as OmpA, OmpC, OmpD, OmpF, OmpX, and NompC. The molecular docking results showed that CBD exhibits varying binding affinities across the OMPs, with OmpX and NompC showing the highest binding affinity of -6.6 kcal/mol and − 6.4 kcal/mol respectively, indicating strong and stable interactions. The results also revealed several key interactions such as hydrogen bonds, Pi-stacking, and hydrophobic interactions, playing crucial roles in the stability and specificity of these protein-ligand complexes. Notable interactions were identified in OmpA with a binding affinity of -5.9 kcal/mol involving hydrogen bonds at 3.2 Å and Pi-Sigma interactions at 3.4 Å. We included phylogenetic analysis of fifty different strains of Salmonella Typhimurium, and we observed high conservation levels among the OMPs, with a sequence similarity threshold of 90%. This high conservation underscores the potential of CBD to act as a broad-spectrum antimicrobial agent. Furthermore, our comparative structural analysis revealed both conserved and variable regions within the OMPs, highlighting the significance of targeting these regions to mitigate resistance development. Using KEGG Pathway analysis, we analyzed OmpC and OmpF, given their roles in nutrient transport and permeability. The disruption of these pathways by CBD binding could impair the bacteria’s ability to manage environmental stresses and evade host immune responses. Beta-lactam resistance pathway analysis was also considered, we observed that CBD could potentially disrupt resistance mechanisms by binding to OMPs, enhancing the efficacy of existing antimicrobial treatments. In conclusion, our findings suggest that CBD, through its interaction with critical OMPs, has the potential to serve as a potent antimicrobial agent against Salmonella Typhimurium LT2. These findings lay the foundation for further studies of CBD as a novel therapeutic agent in combating bacterial infections and addressing the global challenge of antibiotic resistance.
Three-dimensional electromagnetic inversion of transfer function data from controlled sources
Authors: Rulff Paula , Kalscheuer Thomas , Bastani Mehrdad , Zbinden Dominik 
Published: August 2024

Abstract

We develop a three-dimensional inversion code capable of imaging the resistivity distribution of the subsurface from frequency-domain controlled-source electromagnetic data. Controlled-source electromagnetic investigations have, besides other geophysical methods, an important role to play for geophysical prospecting purposes. To analyse controlled-source electromagnetic data collected with complex measurement setups on land, advanced three-dimensional modelling and inversion tools are required.
Therefore, we adopt a preconditioned non-linear conjugate gradient algorithm to be able to invert impedance tensor and vertical magnetic transfer function data produced by multiple sets of two independent active sources. Forward simulations are performed with a finite-element solver. Increased sensitivity at source locations can optionally be counteracted with a weighting function in the regularisation term. We investigate the capabilities of the inversion code using one synthetic and one field example. The results demonstrate, that we can produce reliable subsurface models, although data sets from single pairs of independent sources remain challenging to evaluate due to a nonsymmetric illumination of the target area.
Response of broiler chickens to raw, heat-treated and heat-treated dehulled sweet lupin seed (Lupins angustifolius) meals on feed intake, growth and carcass performances
Authors: Dida Alem , Melesse Aberra 
Published: August 2024

The experiment was conducted to evaluate the effect of the partial substitution of soybean meal with raw and processed lupin seed (Lupinus angustifolius) meals on growth and carcass performances of Cobb 500 broiler chickens. Two hundred unsexed day-old chicks with similar body weight were randomly assigned to four treatment diets in completely randomized design with 5 replicates. The four dietary treatments diets were 0 % lupin seed meal (T1), 15 % raw lupin seed meal (RLS, T2), 15 % heat-treated dehulled lupin seed meal (HDLS, T3) and 15 % heat-treated lupin seed meal (HLS, T4). The CP content of RLS, HDLS, and HLS were 33.5, 37.1, and 35.4 %, respectively. The highest total and daily feed intake was observed in chickens reared in control diet (T1) while the lowest from T2 and T4 diets and differed (p<0.05) with the T1 diet. However, no significance effect was observed in feed conversion ratio among the treatment diets. Chickens fed with T1 diet had higher (p<0.05) final body weight, total and daily weight gains than those reared in T2 and T4 diets while these values were comparable to those fed on T3 diet. Similarly, higher (p<0.05) values were observed for slaughter weight, dressed carcass weight, drumsticks, keel bone meat, wings, neck and back and thorax in chickens fed with T1 diet than those of T2 and T4 diets; but these values did not differ with chickens fed on the T3 diet. The gizzard weight was similar between chickens fed with T1 and T3 diets while those on T2 and T4 diets had lower (p<0.05) values than those of T1 diet. The highest liver weight was observed in T1 diet while the lowest in T2 and differed (p<0.05). In conclusion it would be economically beneficial to replace 15 % of the soybean meal with heat-treated dehulled blue lupin seed meal in broilers ration under tropical environment
Study of the quality indicators of the osmotic solution obtained after dehydration of apricot fruits
Authors: Samilyk Maryna , Tkachuk Mykhaylo 
Published: August 2024

This study is designed to determine the feasibility of using osmotic solutions formed after dehydration of apricot fruits for sugar fortification. The purpose of the study is to analyze the quality indicators of osmotic solutions obtained as a result of osmotic dehydration of apricot fruits and to develop a rational direction for their further use. The subject of the study was apricot fruits (Prunus armeniaca) of the Aurora variety and enriched sugar. It is proposed to enrich sugar with a derivative product formed during the production of candied fruits using the method of osmotic dehydration and drying from apricot fruits. The results of the study showed that, according to organoleptic indicators, the osmotic solution formed after the production of candied apricot fruits corresponded to the raw material. The mass fraction of dry substances in the osmotic solution is reduced by 25,24 %, and sucrose by 20,3 % due to dilution with cell juice of apricot fruits. The osmotic solution had a fairly high color, probably due to saturation with carotenoids, the concentration of which is 15,87 mg/100 ml. Due to the addition of osmotic solutions, the color of sugar increases by 87.3 units. ICUMSA, however, the sugar solution is transparent, without insoluble sediment, mechanical and other impurities. In addition, sugar is enriched with carotenoids, the mass concentration of which is 1.13 mg/100 g. The analysis showed that the addition of osmotic solutions to sugar does not entail a deterioration in their microbiological composition. A model has been developed for the rational processing of apricot fruits and the use of waste osmotic solutions, which can become the basis for sugar enrichment technology
Case-control study to identify management practices associated with morbidity or mortality due to bovine anaplasmosis in Mississippi cow-calf herds
Authors: Jumper W. Isaac , Huston Carla L. , Smith David R. 
Published: August 2024

Bovine anaplasmosis (BA) is a costly disease affecting the U.S. beef cattle industry. Chlortetracycline (CTC) in feed or mineral supplements is often used to control clinical signs of BA. The objective of this study was to determine if manage­ment practices, such as feeding CTC, are associated with ill­ness or death from BA in Mississippi cow-calf herds. Case and control herds were solicited from veterinary practices across Mississippi. Cases were herds with clinical BA diagnosed by a veterinarian within the previous calendar year. Controls were herds under the care of the same practice with no clini­cal BA diagnosed in the previous year. Blinded interviewers conducted telephone surveys of case and control herd owners. Management and biosecurity factors were tested for associa­tion with herd status using a logistic regression generalized linear mixed model with veterinary practice as a random vari­able. Twenty-two case and 25 control herds from 6 veterinary practices across Mississippi were interviewed, representing 22 counties. The average herd size was 132 for case herds, and 136 for control herds. Twenty case herds and 13 control herds fed CTC medicated mineral or feed. Providing CTC was associated with case herd status (OR = 9.2, 95% C.I. = 1.7-50.7). The association observed between case herds and feeding CTC might be because: 1) herds that had experienced previous BA morbidity and mor­tality subsequently began feeding CTC, or 2) some individual cattle consume enough CTC to achieve clearance of the per­sistent carrier state, thereby increasing risk of reinfection and clinical BA.
Pengembangan Game Edukasi Digital Tema Seni dan Bahasa dengan Metode Multimedia Development Life Cycle
Authors: Nurul Hanan , Nugraheni Dinar Mutiara Kusumo , Noranita Beta , Bahtiar Nurdin 
Published: August 2024

Education for early childhood, especially for PAUD TK-B in the age range of 4-6 years, is crucial in providing and shaping the foundation of children's knowledge. An engaging teaching method will enhance children's interest in learning, thus the need for digital learning media as an alternative. One step in implementing digital learning is through Educational Games. This research is conducted by developing the PAUD TK-B Nurussunnah Educational Game using the Multimedia Development Life Cycle (MDLC) method. The game's validation includes usability aspects such as effectiveness, satisfaction levels, and adaptation to the TK-B curriculum. After development, the educational game undergoes alpha and beta testing using the black box method. Beta testing involves evaluating usability for the efficiency and satisfaction of TK-B students, with an effectiveness rate of 98.94% and satisfaction rate of 88.57%. The interview results with expert teachers indicate that the educational game aligns with the curriculum at the educational unit level for PAUD. Thus, based on the research findings, the PAUD TK-B Educational Game application can be considered an alternative learning media for TK-B students.
Use of engineering economic equivalence tenets to prioritize water source(s) for use by households, ‘The Case of Mbeya City – Tanzania’
Authors: Mwishwa Yazidi Hassan Bakari , Shegwando Omari Bakari 
Published: August 2024

ABSTRACT

In Tanzania, inadequate access to water affects 26% of urban and 38% of rural populations, who depend on piped water systems and are often subject to rationing. Low-income households face the significant burden of high water bills and (sometimes) poor water quality. Alternative water sources such as gravity-fed, rainwater harvesting, and drilled well systems are often overlooked, primarily due to the absence of evaluations based on engineering economic equivalence (EEE) principles that determine their viability due to prioritization. This study addresses this gap by analyzing existing literature and utilizing data from Mbeya City, focusing on households relying on tap water, rainwater harvesting, and drilled wells. Engineering Economic Equivalency computations were used to assess the present worth of these water sources, with values determined at Tshs 11,009,424/- for tapped water systems, Tshs 10,283,000/- for rainwater harvesting, and Tshs 12,099,940/- for drilled wells. While rainwater harvesting appears cost-effective, it was found unsuitable for drinking, and tapped water systems incur variable consumption costs. Consequently, the drilled well system is the most sustainable option for ensuring reliable household water access. Households in Mbeya are urged to deploy the engineering economic equivalence principle to prioritize their water-for-own-use.
An Update on Colistin in Clinical Healthcare Unit in the Kingdom of Saudi Arabia: A Narrative Review
Authors: Faidah Hani 
Published: August 2024

:
Globally, gram-negative bacteria are a significant cause of morbidity. Multi-drug resistance bacteria
are responsible for an increasing surge in infections that place a high cost on healthcare systems around the
world. Recently, colistin, an antibiotic belonging to the polymyxin family, was reintroduced to combat multidrug-
resistant gram-negative bacteria. Excessive and persistent use of colistin has led to the development and
spread of colistin-resistant gram-negative bacteria throughout the globe. Healthcare units in various countries,
including Saudi Arabia, are currently battling colistin-resistant gram-negative bacteria. Recently, colistin-resistant
gram-negative bacteria have become a major health concern in Saudi Arabia. Hence, extensive epidemiological
surveys and studies are required to understand the current status of the colistin antibiotic. Examining
the knowledge currently available to the medical community on the molecular mechanism, clinical effectiveness,
molecular epidemiology, and bacterial resistance to colistin in Saudi Arabia is the aim of this review.
Role of Biosynthesis and Catabolism of Neurotransmitters in Drug Discovery for Anxiety and Depression
Authors: Patil Ashish Suresh , Koul Summon 
Published: August 2024

:
The purpose of this review is to correlate the probable causes of anxiety disorders with the imbalance
of neurotransmitters in the brain and also highlight the drugs for these mental disorders that have been discovered
based on the biosynthesis and catabolism of these brain chemicals. Peer-reviewed journal’s articles,
news and books published in English between 1997 and 2023 describing the role of neurotransmitters in anxiety
disorders were searched in Google Scholar, Research Gate and PubMed databases. The contents were carefully
analyzed by the authors and understood and compiled to build a concise perspective on the role of biosynthesis
and catabolism of neurotransmitters in anxiety and depression. Anxiety disorders are reported to be common
patterns of psychological symptoms that impact multiple areas of life. Anxiety and depression are prevalent
worldwide and are significantly contributing towards the global health burden. Genetic determinants are
believed to play an important role in these disorders. According to modern medicine, one of the most important
aspects that is known to be crucial for these disorders is the imbalance of neurotransmitters in the brain.
The biosynthesis and catabolism of neurotransmitters have been extensively targeted for innovative drug discovery
approaches at various steps that have led to the discovery of many drugs for these psychological disorders.
The biosynthetic and catabolic reaction cycles of neurotransmitters and the discovery of drugs based on
these hypotheses are discussed. To the best of the authors’ knowledge, this review compiles already known descriptive
knowledge on “relation of neurotransmitter imbalance with anxiety disorders” in a precise way that
will provide readers with an overview of the vast literature.
Role of P-glycoprotein in Regulating the Efficacy, Toxicity and Pharmacokinetics of Yunaconitine
Authors: Li Xiaocui , Liang Qi , Wang Caiyan , Qiu Huawei , Lin Tingting , Li Wentao , Zhang Rong , Liu Zhongqiu , Zhu Lijun 
Published: August 2024

Background:
Yunaconitine (YAC) is a hidden toxin that greatly threatens the life safety of patients
who are prescribed herbal medicines containing Aconitum species; however, its underlying mechanism remains
unclear.

Objective:
The objective of this study is to elucidate the functions of P-glycoprotein (P-gp) in regulating the efficacy,
toxicity, and pharmacokinetics of YAC.

Methods:
The efflux function of P-gp on YAC was explored by using Caco-2 monolayers in combination with
the P-gp inhibitor verapamil. The impact of P-gp on regulating the analgesic and anti-inflammatory effects,
acute toxicity, tissue distribution, and pharmacokinetics of YAC was determined via male Mdr1a gene
knocked-out mice and wild-type FVB mice

Results:
The presence of verapamil significantly decreased the efflux ratio of YAC from 20.41 to 1.07 in Caco-
2 monolayers (P < 0.05). Moreover, oral administration of 0.07 and 0.14 mg/kg YAC resulted in a notable
decrease in writhing times in Mdr1a-/- mice by 23.53% and 49.27%, respectively, compared to wild-type FVB
mice (P < 0.05). Additionally, the deficiency of P-gp remarkably decreased the half-lethal dose (LD50) of YAC
from 2.13 to 0.24 mg/kg (P < 0.05). Moreover, the concentrations of YAC in the tissues of Mdr1a-/- mice were
statistically higher than those in wild-type FVB mice (P < 0.05). Particularly, the brain accumulation of YAC
in Mdr1a-/- mice significantly increased by 12- and 19-fold, respectively, after oral administration for 30 and
120 min, when compared to wild-type FVB mice (P < 0.05). There were no significant differences in the pharmacokinetic
characteristics of YAC between Mdr1a-/- and wild-type FVB mice.

Conclusion:
YAC is a sensitive substrate of P-gp. The absence of P-gp enhances the analgesic effect and toxicity
of YAC by upregulating its brain accumulation. Co-administration with a P-gp inhibitor may lead to severe
YAC poisoning.
Carboxylesterase 1-Based Drug-Drug Interaction Potential of Remimazolam: In-Vitro Studies and Literature Review
Authors: Petersen Karl-Uwe , Schmalix Wolfgang , Pesic Marija , Stohr Thomas 
Published: August 2024

Background:
The ultra-short-acting benzodiazepine remimazolam, approved for procedural sedation
and general anesthesia, is inactivated by carboxylesterase 1 (CES1).

Objective:
Remimazolam´s involvement in CES1-mediated drug-drug interactions (DDIs) was investigated.

Methods:
Possible interactions of remimazolam were studied in co-exposure experiments with eleven different
drugs. Further, substrates and inhibitors of CES1, identified in the literature, were evaluated for possible
in-vivo inhibition using pharmacokinetic and Ki or IC50 values. Compounds with only one published inhibitory
concentration and CES1 substrates lacking inhibition data were assigned conservative Ki values.

Results:
In human liver homogenates and/or blood cells, remimazolam showed no significant inhibition of
esmolol and landiolol metabolism, which, in turn, at up to 98 and 169 μM, respectively, did not inhibit remimazolam
hydrolysis by human liver homogenates. In human liver S9 fractions, IC50 values ranged from 0.69
μM (simvastatin) and 57 μM (diltiazem) to > 100 μM (atorvastatin) and, for the remaining test items (bupropion,
carvedilol, nelfinavir, nitrendipine, and telmisartan), they ranged from 126 to 658 μM. Remifentanil
was ineffective even at 1250 μM. Guidance-conforming evaluation revealed no relevant drug-drug interactions
with remimazolam via CES1. The algorithm-based predictions were consistent with human study data.
Among CES1 inhibitors and substrates identified in the literature, only dapsone and rufinamide were found to
be possible in-vivo inhibitors of remimazolam metabolism.

Conclusion:
Data and analyses suggest a very low potential of remimazolam for pharmacokinetic DDIs mediated
by CES1. The theoretical approach and compiled data are not specific to remimazolam and, hence,
applicable in the evaluation of other CES1 substrates.
A Compressive Review on Source, Toxicity and Biological Activity of Flavonoid
Authors: Singh Bhoopendra , Semwal Bhupesh Chander 
Published: August 2024

:
Flavonoids are biologically active chemicals in various fruits, plants, vegetables, and
leaves, which have promising uses in medicinal science. The health properties of these natural
chemicals are widely accepted, and efforts are underway to extract the specific components
referred to as flavonoids. Flavonoids demonstrate a diverse range of bio-activities, anticancer,
antioxidant activity, anti-cholinesterase activity, antiinflammatory activity, antimalarial activity,
antidiabetic activity, neurodegenerative disease, cardiovascular effect, hepatoprotective effects,
and antiviral and antimicrobial activity. This study aims to examine the prevailing trends in
flavonoid investigation studies, elucidate the activity of flavonoids, examine their various functions
and uses, assess the potential of flavonoids as preventive medications for chronic diseases,
and outline future research opportunities in this field. This review explores the diverse functions
of flavonoids in preventing and managing various diseases.