bluuebunny/crossref_metadata_2025 huggingface dataset:
Nutrition Value of Baked Meat Products Fortified with Lyophilized Dragon Fruit (Hylocereus undatus)
Authors: Kęska Paulina , Gazda Patrycja , Siłka Łukasz , Mazurek Katarzyna , Stadnik Joanna
Published: September 2023

This study evaluates the nutritional value of a baked pork meat product containing lyophilized dragon fruit pulp. The selected nutritional properties of a baked pork meat product fortified with lyophilized Hylocereus undatus pulp in doses of 0.5%, 1.5%, 2.5%, and 4% were evaluated. For this assessment, changes in the basic chemical composition of the products, the content of calcium, magnesium, potassium, iron, and phosphorus, and the profile of fatty acids were considered. Additionally, characteristics typical for meat products, such as pH, water activity, oxidation-reduction potential or thiobarbituric acid reactive substances, and antioxidant properties of the product during 21 days of refrigerated storage, were assessed. The findings indicate that the use of higher doses of lyophilizate, i.e., in the amounts of 2.5% and 4%, significantly (p < 0.05) increases the nutritional value of meat products, leading to an increase in the concentration of essential minerals important for the proper functioning of the human body (calcium, magnesium, potassium, and iron). These changes occurred without affecting the basic chemical composition (except for an increase in the content of fat and carbohydrates in the sample with the addition of 4% lyophilizate). The introduction of the fortification treatment improved the fatty acid profile, resulting in an increase in the content of C14:0, C16:0, C20:0, and C20:5n3. In addition, in the variant with a 4% dosage, there was an increased content of C8:0, C10:0, C16:1n7, C18:0, C18:1n9C + C18:1n9t, and C18:2n6C + C18:2n6t, C18:3n3 (alpha), C20:1n15, and C20:1n9. In this particular variant, an increase in saturated-, monounsaturated-, and polyunsaturated fatty acids was also observed, which was associated with an increased level of TBARS in meat products. However, the increase in the dose of lyophilizate caused an increase in the antiradical effect of meat extracts. Based on the results obtained, it seems reasonable to use a plant additive in the form of lyophilized dragon fruit pulp in the amount of 4.0% in the production of pork meat products.
Abstract Fractional Cauchy Problem: Existence of Propagators and Inhomogeneous Solution Representation
Authors: Sytnyk Dmytro , Wohlmuth Barbara
Published: September 2023

We consider a Cauchy problem for the inhomogeneous differential equation given in terms of an unbounded linear operator A and the Caputo fractional derivative of order α∈(0,2) in time. The previously known representation of the mild solution to such a problem does not have a conventional variation-of-constants like form, with the propagator derived from the associated homogeneous problem. Instead, it relies on the existence of two propagators with different analytical properties. This fact limits theoretical and especially numerical applicability of the existing solution representation. Here, we propose an alternative representation of the mild solution to the given problem that consolidates the solution formulas for sub-parabolic, parabolic and sub-hyperbolic equations with a positive sectorial operator A and non-zero initial data. The new representation is solely based on the propagator of the homogeneous problem and, therefore, can be considered as a more natural fractional extension of the solution to the classical parabolic Cauchy problem. By exploiting a trade-off between the regularity assumptions on the initial data in terms of the fractional powers of A and the regularity assumptions on the right-hand side in time, we show that the proposed solution formula is strongly convergent for t≥0 under considerably weaker assumptions compared to the standard results from the literature. Crucially, the achieved relaxation of space regularity assumptions ensures that the new solution representation is practically feasible for any α∈(0,2) and is amenable to the numerical evaluation using uniformly accurate quadrature-based algorithms.
Fractal Characteristics of Overburden Rock Fractures and Their Impact on Ground Fissures in Longwall Coal Mining
Authors: Ling Chunwei , Liu Bin , Zhang Cun , Teng Teng , Zhang Kangning , Sun Bo , Zhou Jinlong
Published: September 2023

Ground fissures are generated during the coal mining process due to overlying strata migration, which provides gas and water seepage channels and usually contributes to coal mining accidents in shallow buried coal seams with larger mining height working faces. Thus, the evolution features of ground fissures in large mining height working faces and shallow buried coal seams were explored by considering field observation data, similar simulation, and numerical simulations. The results show that the weathered rock layer above the thin bedrock inhibits fracture growth caused by coal mining. Overlying strata fracture expansion can be quantitatively divided into three stages based on fractal dimension: the overburden fracture formation stage, the overburden deformation fracture expansion stage, and the overburden fracture stable development stage. The movement deformation region of the ground fissure can be described by three characteristic zones: the boundary tension zone, the central compression zone, and the central dynamic tension and compression zone. Central dynamic fissures usually have 3–5 fissure counts with 2–5 m intervals between each group of fissures; central fissures develop twice from open to closed widths; the time period for two central fissures to reach their with maximum widths is 11–20 days; and border fissures expand rapidly with maximum values in a time period of 5–6 days.
Three General Double-Series Identities and Associated Reduction Formulas and Fractional Calculus
Authors: Qureshi Mohd Idris , Shah Tafaz Ul Rahman , Choi Junesang , Bhat Aarif Hussain
Published: September 2023

In this article, we introduce three general double-series identities using Whipple transformations for terminating generalized hypergeometric 4F3 and 5F4 functions. Then, by employing the left-sided Riemann–Liouville fractional integral on these identities, we show the ability to derive additional identities of the same nature successively. These identities are used to derive transformation formulas between the Srivastava–Daoust double hypergeometric function (S–D function) and Kampé de Fériet’s double hypergeometric function (KDF function) with equal arguments. We also demonstrate reduction formulas from the S–D function or KDF function to the generalized hypergeometric function pFq. Additionally, we provide general summation formulas for the pFq and S–D function (or KDF function) with specific arguments. We further highlight the connections between the results presented here and existing identities.
A Fractional (q,q′) Non-Extensive Information Dimension for Complex Networks
Authors: Ramirez-Arellano Aldo , De-la-Cruz-Garcia Jazmin-Susana , Bory-Reyes Juan
Published: September 2023

This article introduces a new fractional approach to the concept of information dimensions in complex networks based on the (q,q′)-entropy proposed in the literature. The q parameter measures how far the number of sub-systems (for a given size ε) is from the mean number of overall sizes, whereas q′ (the interaction index) measures when the interactions between sub-systems are greater (q′>1), lesser (q′<1), or equal to the interactions into these sub-systems. Computation of the proposed information dimension is carried out on several real-world and synthetic complex networks. The results for the proposed information dimension are compared with those from the classic information dimension based on Shannon entropy. The obtained results support the conjecture that the fractional (q,q′)-information dimension captures the complexity of the topology of the network better than the information dimension.
A New Hybrid Block Method for Solving First-Order Differential System Models in Applied Sciences and Engineering
Authors: Rufai Mufutau Ajani , Carpentieri Bruno , Ramos Higinio
Published: September 2023

This paper presents a new hybrid block method formulated in variable stepsize mode to solve some first-order initial value problems of ODEs and time-dependent partial differential equations in applied sciences and engineering. The proposed method is implemented considering an adaptive stepsize strategy to maintain the estimated error in each step within a specified tolerance. In order to evaluate the performance and usefulness of the proposed technique in real-world applications, several differential problems from applied sciences and engineering, such as the SIR model, Jacobi elliptic function problem, and chemical reactions problems, are solved numerically. The results of numerical simulations in this work demonstrate that the proposed method is more efficient than other existing numerical methods used for comparisons.
Tailoring Homogeneous Hydrogel Nanospheres by Facile Ultra-Sonication Assisted Cross-Linked Copolymerization for Rhodamine B Dye Adsorption
Authors: Sharma Gaurav , García-Peñas Alberto , Verma Yaksha , Kumar Amit , Dhiman Pooja , Stadler Florian J.
Published: September 2023

The present paper describes the design of shape-oriented hydrogel nanospheres using a facile ultrasonication-supported crosslinked copolymerization technique. The effect of variable monomer concentration on the homogeneity of hydrogel nanospheres was investigated. The chitosan-cl-poly(MMA) hydrogel nanospheres were well characterized using various techniques such as FTIR, XRD, TGA, SEM, and TEM. The chitosan-cl-poly(MMA) hydrogel nanospheres were studied for their swelling behavior and could potentially be used as a novel adsorbent for rhodamine B dye remediation from aqueous media. The study found that utilizing chitosan-cl-poly(MMA) nanohydrogel spheres at the optimal pH 5 increased RhB dye adsorption capacity from 7.9 to 17.8 mg/g (pH 2 to 5), followed by a slight reduction. Furthermore, when nanohydrogel concentration increased, adsorption capacity dropped from 18.03 to 2.8 mg/g, but adsorption percentage climbed from 90.2% to 97.8%. At an initial dye concentration of 140 mg/L, rhodamine B adsorption achieved 204.3 mg/g in 60 min. The rhodamine B dye adsorption study includes adsorption kinetics, isotherm, and thermodynamics analyses. The interpretation of the adsorption study revealed that Langmuir isotherms fit best with a qmax value of 276.26 mg/g, which is in close approximation with the experimental value, whereas pseudo-second-order kinetics explains the adsorption process rate. The interaction of RhB dye with chitosan-cl-poly(MMA) hydrogel nanospheres involves multiple forces such as electrostatic interactions, hydrogen bonding, van der Waals forces, etc.
Nanoparticle Dynamics in Composite Hydrogels Exposed to Low-Frequency Focused Ultrasound
Authors: Einen Caroline , Price Sebastian E. N. , Ulvik Kim , Gjennestad Magnus Aa. , Hansen Rune , Kjelstrup Signe , Davies Catharina de Lange
Published: September 2023

Pulsed focused ultrasound (FUS) in combination with microbubbles has been shown to improve delivery and penetration of nanoparticles in tumors. To understand the mechanisms behind this treatment, it is important to evaluate the contribution of FUS without microbubbles on increased nanoparticle penetration and transport in the tumor extracellular matrix (ECM). A composite agarose hydrogel was made to model the porous structure, the acoustic attenuation and the hydraulic conductivity of the tumor ECM. Single-particle tracking was used as a novel method to monitor nanoparticle dynamics in the hydrogel during FUS exposure. FUS exposure at 1 MHz and 1 MPa was performed to detect any increase in nanoparticle diffusion or particle streaming at acoustic parameters relevant for FUS in combination with microbubbles. Results were compared to a model of acoustic streaming. The nanoparticles displayed anomalous diffusion in the hydrogel, and FUS with a duty cycle of 20% increased the nanoparticle diffusion coefficient by 23%. No increase in diffusion was found for lower duty cycles. FUS displaced the hydrogel itself at duty cycles above 10%; however, acoustic streaming was found to be negligible. In conclusion, pulsed FUS alone cannot explain the enhanced penetration of nanoparticles seen when using FUS and microbubbles for nanoparticle delivery, but it could be used as a tool to enhance diffusion of particles in the tumor ECM.
Double Cross-Linked Chitosan/Bacterial Cellulose Dressing with Self-Healable Ability
Authors: Deng Lili , Ou Kangkang , Shen Jiaxin , Wang Baoxiu , Chen Shiyan , Wang Huaping , Gu Song
Published: September 2023

Self-healing hydrogel products have attracted a great deal of interest in wound healing due to their ability to repair their own structural damage. Herein, an all-natural self-healing hydrogel based on methacrylated chitosan (CSMA) and dialdehyde bacterial cellulose (DABC) is developed. MA is used to modify CS and obtain water-soluble biomaterial-based CSMA with photo crosslinking effects. BC is modified through a simple oxidation method to gain dialdehyde on the polymer chain. The success of the modification is confirmed via FTIR. Hydrogels are formed within 11 min through the establishment of a Schiff base between the amino of CSMA and the aldehyde of DABC. A dynamically reversible Schiff base bond endows hydrogel with good self-healing properties through macroscopic and microscopic observations. We observe the uniform and porous structure in the hydrogel using SEM images, and DABC nanofibers are found to be well distributed in the hydrogel. The compressive strength of the hydrogel is more than 20 kPa and the swelling rate sees over a 10-fold increase. In addition, the CSMA/DABC hydrogel has good cytocompatibility, with cell viability exceeding 90%. These results indicate that the all-natural self-healable CSMA/DABC hydrogel demonstrates strong application potential in wound healing and tissue repair.
A Study of the Properties of Scaffolds for Bone Regeneration Modified with Gel-like Coatings of Chitosan and Folic Acid
Authors: Bandzerewicz Aleksandra , Godzieba Kamila , Wierzchowski Kamil , Pilarek Maciej , Gadomska-Gajadhur Agnieszka
Published: September 2023

The research has been conducted to obtain scaffolds for cancellous bone regeneration. Polylactide scaffolds were made by the phase inversion method with a freeze-extraction variant, including gelling polylactide in its non-solvent. Substitutes made of polylactide are hydrophobic, which limits cell adhesion. For this reason, the scaffolds were modified using chitosan and folic acid by forming gel-like coatings on the surface. The modification aimed to improve the material’s surface properties and increase cell adhesion. Analyses of obtained scaffolds confirmed the effectiveness of performed changes. The presence of chitosan and folic acid was confirmed in the modified scaffolds, while all scaffolds retained high open porosity, which is essential for proper cell growth inside the scaffold and the free flow of nutrients. Hydrostatic weighing showed that the scaffolds have high mass absorbability, allowing them to be saturated with biological fluids. There were also cytotoxicity tests performed on 24 h extracts of the materials obtained, which indicated a lack of cytotoxic effect.
Enhancing Rheological and Textural Properties of Gelatin-Based Composite Gels through Incorporation of Sesame Seed Oleosome-Protein Fillers
Authors: Sheikh Fatemeh , Hasani Maryam , Kiani Hossein , Asadollahzadeh Mohammad Javad , Sabbagh Farzaneh
Published: September 2023

In this study, the protein and oleosomes of sesame seeds were extracted individually and used to prepare a gel composed of gelatin, protein, and oleosomes. Mixtures of gelatin and sesame seeds protein were prepared, and oleosomes with different percentages (0, 10, 20 and 30% of their weight) were used. Different amounts of oleosomes in the composite gel samples were examined for their morphological, rheological, and textural properties. The results of the viscoelastic properties of different composite gel samples indicated that a higher percentage of oleosomes would increase the storage modulus (G′), loss modulus (G″), and complex viscosity (η*). The storage modulus of all gel samples was greater than the loss modulus, suggesting a solid behavior. So, in the sample with 30% oleosome, the storage modulus and the loss modulus reached 143,440 Pascals and 44,530 Pascals. The hardness and breaking force in samples containing 30% oleosome reached 1.29 ± 0.02 and 0.17 ± 0.02, respectively. In general, it can be said that composite gels based on gelatin-sesame seed protein modified with oleosome can be used as a part of food components in various dairy products, gelatin desserts, lean meat products and the production of useful products.
Polymeric Materials for Rare Earth Elements Recovery
Authors: Zhang Hongtao , Gao Yongfeng
Published: September 2023

Rare earth elements (REEs) play indispensable roles in various advanced technologies, from electronics to renewable energy. However, the heavy global REEs supply and the environmental impact of traditional mining practices have spurred the search for sustainable REEs recovery methods. Polymeric materials have emerged as promising candidates due to their selective adsorption capabilities, versatility, scalability, and regenerability. This paper provides an extensive overview of polymeric materials for REEs recovery, including polymeric resins, polymer membranes, cross-linked polymer networks, and nanocomposite polymers. Each category is examined for its advantages, challenges, and notable developments. Furthermore, we highlight the potential of polymeric materials to contribute to eco-friendly and efficient REEs recovery, while acknowledging the need to address challenges such as selectivity, stability, and scalability. The research in this field actively seeks innovative solutions to reduce reliance on hazardous chemicals and minimize waste generation. As the demand for REEs continues to rise, the development of sustainable REEs recovery technologies remains a critical area of investigation, with the collaboration between researchers and industry experts driving progress in this evolving field.
SNPtotree—Resolving the Phylogeny of SNPs on Non-Recombining DNA
Authors: Köksal Zehra , Børsting Claus , Gusmão Leonor , Pereira Vania
Published: September 2023

Genetic variants on non-recombining DNA and the hierarchical order in which they accumulate are commonly of interest. This variant hierarchy can be established and combined with information on the population and geographic origin of the individuals carrying the variants to find population structures and infer migration patterns. Further, individuals can be assigned to the characterized populations, which is relevant in forensic genetics, genetic genealogy, and epidemiologic studies. However, there is currently no straightforward method to obtain such a variant hierarchy. Here, we introduce the software SNPtotree v1.0, which uniquely determines the hierarchical order of variants on non-recombining DNA without error-prone manual sorting. The algorithm uses pairwise variant comparisons to infer their relationships and integrates the combined information into a phylogenetic tree. Variants that have contradictory pairwise relationships or ambiguous positions in the tree are removed by the software. When benchmarked using two human Y-chromosomal massively parallel sequencing datasets, SNPtotree outperforms traditional methods in the accuracy of phylogenetic trees for sequencing data with high amounts of missing information. The phylogenetic trees of variants created using SNPtotree can be used to establish and maintain publicly available phylogeny databases to further explore genetic epidemiology and genealogy, as well as population and forensic genetics.
Whole-Exome Sequencing of 24 Spanish Families: Candidate Genes for Non-Syndromic Pediatric Keratoconus
Authors: González-Atienza Carmen , Sánchez-Cazorla Eloísa , Villoldo-Fernández Natalia , del Hierro Almudena , Boto Ana , Guerrero-Carretero Marta , Nieves-Moreno María , Arruti Natalia , Rodríguez-Solana Patricia , Mena Rocío , Rodríguez-Jiménez Carmen , Rosa-Pérez Irene , Acal Juan Carlos , Blasco Joana , Naranjo-Castresana Marta , Ruz-Caracuel Beatriz , Montaño Victoria E. F. , Ortega Patrón Cristina , Rubio-Martín M. Esther , García-Fernández Laura , Rikeros-Orozco Emi , Gómez-Cano María de Los Ángeles , Delgado-Mora Luna , Noval Susana , Vallespín Elena
Published: September 2023

Keratoconus is a corneal dystrophy that is one of the main causes of corneal transplantation and for which there is currently no effective treatment for all patients. The presentation of this disease in pediatric age is associated with rapid progression, a worse prognosis and, in 15–20% of cases, the need for corneal transplantation. It is a multifactorial disease with genetic variability, which makes its genetic study difficult. Discovering new therapeutic targets is necessary to improve the quality of life of patients. In this manuscript, we present the results of whole-exome sequencing (WES) of 24 pediatric families diagnosed at the University Hospital La Paz (HULP) in Madrid. The results show an oligogenic inheritance of the disease. Genes involved in the structure, function, cell adhesion, development and repair pathways of the cornea are proposed as candidate genes for the disease. Further studies are needed to confirm the involvement of the candidate genes described in this article in the development of pediatric keratoconus.
Identification of Missense Variants Affecting Carcass Traits for Hanwoo Precision Breeding
Authors: Lee Dong Jae , Kim Yoonsik , Dinh Phuong Thanh N. , Chung Yoonji , Lee Dooho , Kim Yeongkuk , Lee Soo Hyun , Choi Inchul , Lee Seung Hwan
Published: September 2023

This study aimed to identify causal variants associated with important carcass traits such as weight and meat quality in Hanwoo cattle. We analyzed missense mutations extracted from imputed sequence data (ARS-UCD1.2) and performed an exon-specific association test on the carcass traits of 16,970 commercial Hanwoo. We found 33, 2, 1, and 3 significant SNPs associated with carcass weight (CW), backfat thickness (BFT), eye muscle area (EMA), and marbling score (MS), respectively. In CW and EMA, the most significant missense SNP was identified at 19,524,263 on BTA14 and involved the PRKDC. A missense SNP in the ZFAND2B, located at 107,160,304 on BTA2 was identified as being involved in BFT. For MS, missense SNP in the ACVR2B gene, located at 11,849,704 in BTA22 was identified as the most significant marker. The contribution of the most significant missense SNPs to genetic variance was confirmed to be 8.47%, 2.08%, 1.73%, and 1.19% in CW, BFT, EMA, and MS, respectively. We generated favorable and unfavorable haplotype combinations based on the significant SNPs for CW. Significant differences in GEBV (Genomic Estimated Breeding Values) were observed between groups with each favorable and unfavorable haplotype combination. In particular, the missense SNPs in PRKDC, MRPL9, and ANKFN1 appear to significantly affect the protein’s function and structure, making them strong candidates as causal mutations. These missense SNPs have the potential to serve as valuable markers for improving carcass traits in Hanwoo commercial farms.
Population Pharmacogenomics for Health Equity
Authors: Jordan I. King , Sharma Shivam , Mariño-Ramírez Leonardo
Published: September 2023

Health equity means the opportunity for all people and populations to attain optimal health, and it requires intentional efforts to promote fairness in patient treatments and outcomes. Pharmacogenomic variants are genetic differences associated with how patients respond to medications, and their presence can inform treatment decisions. In this perspective, we contend that the study of pharmacogenomic variation within and between human populations—population pharmacogenomics—can and should be leveraged in support of health equity. The key observation in support of this contention is that racial and ethnic groups exhibit pronounced differences in the frequencies of numerous pharmacogenomic variants, with direct implications for clinical practice. The use of race and ethnicity to stratify pharmacogenomic risk provides a means to avoid potential harm caused by biases introduced when treatment regimens do not consider genetic differences between population groups, particularly when majority group genetic profiles are assumed to hold for minority groups. We focus on the mitigation of adverse drug reactions as an area where population pharmacogenomics can have a direct and immediate impact on public health.
Implementation of Pharmacogenetics in First-Line Care: Evaluation of Its Use by General Practitioners
Authors: van der Drift Denise , Simoons Mirjam , Koch Birgit C. P. , Brufau Gemma , Bindels Patrick , Matic Maja , van Schaik Ron H. N.
Published: September 2023

Pharmacogenetics (PGx) can explain/predict drug therapy outcomes. There is, however, unclarity about the use and usefulness of PGx in primary care. In this study, we investigated PGx tests ordered by general practitioners (GPs) in 2021 at Dept. Clinical Chemistry, Erasmus MC, and analyzed the gene tests ordered, drugs/drug groups, reasons for testing and single-gene versus panel testing. Additionally, a survey was sent to 90 GPs asking about their experiences and barriers to implementing PGx. In total, 1206 patients and 6300 PGx tests were requested by GPs. CYP2C19 was requested most frequently (17%), and clopidogrel was the most commonly indicated drug (23%). Regarding drug groups, antidepressants (51%) were the main driver for requesting PGx, followed by antihypertensives (26%). Side effects (79%) and non-response (27%) were the main indicators. Panel testing was preferred over single-gene testing. The survey revealed knowledge on when and how to use PGx as one of the main barriers. In conclusion, PGx is currently used by GPs in clinical practice in the Netherlands. Side effects are the main reason for testing, which mostly involves antidepressants. Lack of knowledge is indicated as a major barrier, indicating the need for more education on PGx for GPs.
Genetic Distinctness and Diversity of American Aberdeen Cattle Compared to Common Beef Breeds in the United States
Authors: Bhowmik Nayan , Seaborn Travis , Ringwall Kris A. , Dahlen Carl R. , Swanson Kendall C. , Hulsman Hanna Lauren L.
Published: September 2023

American Aberdeen (AD) cattle in the USA descend from an Aberdeen Angus herd originally brought to the Trangie Agricultural Research Centre, New South Wales, AUS. Although put under specific selection pressure for yearling growth rate, AD remain genomically uncharacterized. The objective was to characterize the genetic diversity and structure of purebred and crossbred AD cattle relative to seven common USA beef breeds using available whole-genome SNP data. A total of 1140 animals consisting of 404 purebred (n = 8 types) and 736 admixed individuals (n = 10 types) was used. Genetic diversity metrics, an analysis of molecular variance, and a discriminant analysis of principal components were employed. When linkage disequilibrium was not accounted for, markers influenced basic diversity parameter estimates, especially for AD cattle. Even so, intrapopulation and interpopulation estimates separate AD cattle from other purebred types (e.g., Latter’s pairwise FST ranged from 0.1129 to 0.2209), where AD cattle were less heterozygous and had lower allelic richness than other purebred types. The admixed AD-influenced cattle were intermediate to other admixed types for similar parameters. The diversity metrics separation and differences support strong artificial selection pressures during and after AD breed development, shaping the evolution of the breed and making them genomically distinct from similar breeds.
Association between Gastric Cancer and 12 Autoimmune Diseases: A Mendelian Randomization Study
Authors: Wei Qi , Wang Ziyu , Liu Xuanyu , Liang Haibin , Chen Lei
Published: September 2023

Background: Whether the positive associations of gastric cancer (GC) with autoimmune diseases are causal has always been controversial. This study aims to estimate the causal relationship between GC and 12 autoimmune diseases by means of Mendelian randomization (MR) analysis. Methods: After rigorous evaluation, potential candidate single nucleotide polymorphisms (SNPs) for GC and 12 autoimmune diseases were extracted from genome-wide association study (GWAS) datasets. We performed the MR analyses using the inverse variance weighted (IVW) method as the primary approach to the analysis. Three sensitivity analysis methods were added to assess the robustness of the results. In addition, heterogeneity was measured using Cochran’s Q-value, and horizontal pleiotropy was assessed using MR-Egger regression and leave-one-out analysis. Results: The IVW result, which is the main method of analysis, shows no evidence of a causal association between GC and any autoimmune disease. The results of IVW analysis show the relationship between rheumatoid arthritis (p = 0.1389), systemic lupus erythematosus (p = 0.1122), Crohn‘s disease (p = 0.1509), multiple sclerosis (p = 0.3944), primary sclerosing cholangitis (p = 0.9022), primary biliary cirrhosis (p = 0.7776), type 1 diabetes (p = 0.9595), ulcerative colitis (p = 0.5470), eczema (p = 0.3378), asthma (p = 0.7436), celiac disease (p = 0.4032), and psoriasis (p = 0.7622) and GC susceptibility. The same result was obtained with the weighted median and the MR-egger (p > 0.05). Conclusion: Our study did not find a genetic causal relationship between susceptibility to these autoimmune diseases and GC, which suggests that unmeasured confounders (e.g., inflammatory processes) or shared genetic architecture may be responsible for the reported epidemiologic associations. Further studies of ancestral diversity are warranted to validate such causal associations.
INPP5D/SHIP1: Expression, Regulation and Roles in Alzheimer’s Disease Pathophysiology
Authors: Olufunmilayo Edward O. , Holsinger R. M. Damian
Published: September 2023

Alzheimer’s disease (AD) is the most common form of dementia, accounting for approximately 38.5 million cases of all-cause dementia. Over 60% of these individuals live in low- and middle-income countries and are the worst affected, especially by its deleterious effects on the productivity of both patients and caregivers. Numerous risk factors for the disease have been identified and our understanding of gene–environment interactions have shed light on several gene variants that contribute to the most common, sporadic form of AD. Microglial cells, the innate immune cells of the central nervous system (CNS), have long been established as guardians of the brain by providing neuroprotection and maintaining cellular homeostasis. A protein with a myriad of effects on various important signaling pathways that is expressed in microglia is the Src Homology 2 (SH2) domain-containing Inositol 5′ Phosphatase 1 (SHIP1) protein. Encoded by the INPP5D (Inositol Polyphosphate-5-Phosphatase D) gene, SHIP1 has diminutive effects on most microglia signaling processes. Polymorphisms of the INPP5D gene have been found to be associated with a significantly increased risk of AD. Several studies have elucidated mechanistic processes by which SHIP1 exerts its perturbations on signaling processes in peripheral immune cells. However, current knowledge of the controllers of INPP5D/SHIP1 expression and the idiosyncrasies of its influences on signaling processes in microglia and their relevance to AD pathophysiology is limited. In this review, we summarize these discoveries and discuss the potential of leveraging INPP5D/SHIP1 as a therapeutic target for Alzheimer’s disease.
LRP5, Bone Mass Polymorphisms and Skeletal Disorders
Authors: Littman Jake , Yang Wentian , Olansen Jon , Phornphutkul Chanika , Aaron Roy K.
Published: September 2023

The formation and maintenance of the gross structure and microarchitecture of the human skeleton require the concerted functioning of a plethora of morphogenic signaling processes. Through recent discoveries in the field of genetics, numerous genotypic variants have been implicated in pathologic skeletal phenotypes and disorders arising from the disturbance of one or more of these processes. For example, total loss-of-function variants of LRP5 were found to be the cause of osteoporosis-pseudoglioma syndrome (OPPG). LRP5 encodes for the low-density lipoprotein receptor-related protein 5, a co-receptor in the canonical WNT–β-catenin signaling pathway and a crucial protein involved in the formation and maintenance of homeostasis of the human skeleton. Beyond OPPG, other partial loss-of-function variants of LRP5 have been found to be associated with other low bone mass phenotypes and disorders, while LRP5 gain-of-function variants have been implicated in high bone mass phenotypes. This review introduces the roles that LRP5 plays in skeletal morphogenesis and discusses some of the structural consequences that result from abnormalities in LRP5. A greater understanding of how the LRP5 receptor functions in bone and other body tissues could provide insights into a variety of pathologies and their potential treatments, from osteoporosis and a variety of skeletal abnormalities to congenital disorders that can lead to lifelong disabilities.
Comparative Studies on Duplicated foxl2 Paralogs in Spotted Knifejaw Oplegnathus punctatus Show Functional Diversification
Authors: Du Xinxin , Yu Haiyang , Wang Yujue , Liu Jinxiang , Zhang Quanqi
Published: September 2023

As a member of the forkhead box L gene family, foxl2 plays a significant role in gonadal development and the regulation of reproduction. During the evolution of deuterostome, whole genome duplication (WGD)-enriched lineage diversifications and regulation mechanisms occurs. However, only limited research exists on foxl2 duplication in teleost or other vertebrate species. In this study, two foxl2 paralogs, foxl2 and foxl2l, were identified in the transcriptome of spotted knifejaw (Oplegnathus punctatus), which had varying expressions in the gonads. The foxl2 was expressed higher in the ovary, while foxl2l was expressed higher in the testis. Phylogenetic reconstruction, synteny analysis, and the molecular evolution test confirmed that foxl2 and foxl2l likely originated from the first two WGD. The expression patterns test using qRT-PCR and ISH as well as motif scan analysis revealed evidence of potentially functional divergence between the foxl2 and foxl2l paralogs in spotted knifejaw. Our results indicate that foxl2 and foxl2l may originate from the first two WGD, be active in transcription, and have undergone functional divergence. These results shed new light on the evolutionary trajectories of foxl2 and foxl2l and highlights the need for further detailed functional analysis of these two duplicated paralogs.
Transcriptome and Metabolome Analyses Reveal the Mechanism of Corpus Luteum Cyst Formation in Pigs
Authors: Dai Jiage , Cai Jiabao , Zhang Taipeng , Pang Mingyue , Xu Xiaoling , Bai Jiahua , Liu Yan , Qin Yusheng
Published: September 2023

Corpus luteum cysts are a serious reproductive disorder that affects the reproductive performance of sows. In this study, transcriptome and metabolome datasets of porcine normal and cyst luteal granulosa cells were generated to explore the molecular mechanism of luteal cyst formation. We obtained 28.9 Gb of high−quality transcriptome data from luteum tissue samples and identified 1048 significantly differentially expressed genes between the cyst and normal corpus luteum samples. Most of the differentially expressed genes were involved in cancer and immune signaling pathways. Furthermore, 22,622 information-containing positive and negative ions were obtained through gas chromatography−mass spectrometry, and 1106 metabolites were successfully annotated. Important differentially abundant metabolites and pathways were identified, among which abnormal lipid and choline metabolism were involved in the formation of luteal cysts. The relationships between granulosa cells of luteal cysts and cancer, immune-related signaling pathways, and abnormalities of lipid and choline metabolism were elaborated, providing new entry points for studying the pathogenesis of porcine luteal cysts.
Oncomeric Profiles of microRNAs as New Therapeutic Targets for Treatment of Ewing’s Sarcoma: A Composite Review
Authors: Hassan Mubashir , Shahzadi Saba , Malik Amal , Din Salah ud , Yasir Muhammad , Chun Wanjoo , Kloczkowski Andrzej
Published: September 2023

Ewing’s sarcoma is a rare type of cancer that forms in bones and soft tissues in the body, affecting mostly children and young adults. Current treatments for ES are limited to chemotherapy and/or radiation, followed by surgery. Recently, microRNAs have shown favourable results as latent diagnostic and prognostic biomarkers in various cancers. Furthermore, microRNAs have shown to be a good therapeutic agent due to their involvement in the dysregulation of various molecular pathways linked to tumour progression, invasion, angiogenesis, and metastasis. In this review, comprehensive data mining was employed to explore various microRNAs that might have therapeutic potential as target molecules in the treatment of ES.
Rapid Visual Detection of High Nitrogen-Use Efficiency Gene OsGRF4 in Rice (Oryza sativa L.) Using Loop-Mediated Isothermal Amplification Method
Authors: Tian Yonghang , Ye Wenwei , Liang Xiangshuai , Xu Peizhou , Wu Xianjun , Fu Xiangdong , Chin Yaoxian , Liao Yongxiang
Published: September 2023

The GROWTH-REGULATING FACTOR4 (OsGRF4) allele is an important target for the development of new high nitrogen-use efficiency (NUE) rice lines that would require less fertilizers. Detection of OsGRF4 through PCR (polymerase chain reaction)-based assay is cumbersome and needs advanced laboratory skills and facilities. Hence, a method for conveniently and rapidly detecting OsGRF4 on-field is a key requirement for further research and applications. In this study, we employed cleaved amplified polymorphic sequences (CAPs) and loop-mediated isothermal amplification (LAMP) techniques to develop a convenient visual detection method for high NUE gene OsGRF4NM73 (OsGRF4 from the rice line NM73). The TC→AA mutation at 1187–1188 bp loci was selected as the target sequence for the OsGRF4NM73 allele. We further employed this method of identification in 10 rice varieties that carried the OsGRF4 gene and results revealed that one variety (NM73) carries the target OsGRF4NM73 allele, while other varieties did not possess the osgrf4 genotype. The optimal LAMP reaction using hydroxynaphthol blue (HNB), a chromogenic indicator, was carried out at 65 °C for 60 min, and the presence of OsGRF4NM73 allele was confirmed by color changes from violet to sky blue. The results of this study showed that the LAMP method can be conveniently and accurately used to detect the OsGRF4NM73 gene in rice.
Complex Genomic Rearrangements Involving ETV6::ABL1 Gene Fusion in an Individual with Myeloid Neoplasm
Authors: Qi Zhongxia , Smith Catherine , Shah Neil P. , Yu Jingwei
Published: September 2023

ETV6::ABL1 gene fusion is a rare recurrent genomic rearrangement associated with hematologic malignancies, and frequently occurs with additional anomalies. Due to the opposite chromosome orientations of the ETV6 and ABL1 genes, an oncogenic in-frame ETV6::ABL1 gene fusion cannot be formed by a simple translocation. The molecular mechanism of the ETV6::ABL1 fusion and the significance of co-occurring anomalies are not fully understood. We characterized genomic alterations in an individual with ETV6::ABL1 gene-fusion-positive myeloid neoplasm using various genomic technologies. Our findings uncovered a molecular mechanism of the ETV6::ABL1 fusion, in which a paracentric inversion within the short arm of chromosome 12 (12p) and a translocation between the long arm of a chromosome 9 and the 12p with the inversion were involved. In addition, we detected multiple additional anomalies in the individual, and our findings suggested that the ETV6::ABL1 fusion occurred as a secondary event in a subset of cells with the additional anomalies. We speculate that the additional anomalies may predispose to further pathogenic changes, including ETV6::ABL1 fusion, leading to neoplastic transformation.
Molecular Characterization of Complete Genome Sequence of an Avian Coronavirus Identified in a Backyard Chicken from Tanzania
Authors: Kariithi Henry M. , Volkening Jeremy D. , Chiwanga Gaspar H. , Goraichuk Iryna V. , Msoffe Peter L. M. , Suarez David L.
Published: September 2023

A complete genome sequence of an avian coronavirus (AvCoV; 27,663 bp excluding 3′ poly(A) tail) was determined using nontargeted next-generation sequencing (NGS) of an oropharyngeal swab from a backyard chicken in a live bird market in Arusha, Tanzania. The open reading frames (ORFs) of the Tanzanian strain TZ/CA127/19 are organized as typical of gammaCoVs (Coronaviridae family): 5′UTR-[ORFs 1a/1b encoding replicase complex (Rep1ab) non-structural peptides nsp2-16]-[spike (S) protein]-[ORFs 3a/3b]-[small envelop (E) protein]-[membrane (M) protein]-[ORFs 4a/4c]-[ORFs 5a/5b]-[nucleocapsid (N) protein]-[ORF6b]-3′UTR. The structural (S, E, M and N) and Rep1ab proteins of TZ/CA127/19 contain features typically conserved in AvCoVs, including the cleavage sites and functional motifs in Rep1ab and S. Its genome backbone (non-spike region) is closest to Asian GI-7 and GI-19 infectious bronchitis viruses (IBVs) with 87.2–89.7% nucleotide (nt) identities, but it has a S gene closest (98.9% nt identity) to the recombinant strain ck/CN/ahysx-1/16. Its 3a, 3b E and 4c sequences are closest to the duck CoV strain DK/GD/27/14 at 99.43%, 100%, 99.65% and 99.38% nt identities, respectively. Whereas its S gene phylogenetically cluster with North American TCoVs and French guineafowl COVs, all other viral genes group monophyletically with Eurasian GI-7/GI-19 IBVs and Chinese recombinant AvCoVs. Detection of a 4445 nt-long recombinant fragment with breakpoints at positions 19,961 and 24,405 (C- and N-terminus of nsp16 and E, respectively) strongly suggested that TZ/CA127/19 acquired its genome backbone from an LX4-type (GI-19) field strain via recombination with an unknown AvCoV. This is the first report of AvCoV in Tanzania and leaves unanswered the questions of its emergence and the biological significance.
High Mitochondrial Haplotype Diversity Found in Three Pre-Hispanic Groups from Colombia
Authors: Uricoechea Patiño Daniel , Collins Andrew , García Oscar Julián Romero , Santos Vecino Gustavo , Cuenca José Vicente Rodríguez , Bernal Jaime E. , Benavides Benítez Escilda , Vergara Muñoz Saray , Briceño Balcázar Ignacio
Published: September 2023

The analysis of mitochondrial DNA (mtDNA) hypervariable region (HVR) sequence data from ancient human remains provides valuable insights into the genetic structure and population dynamics of ancient populations. mtDNA is particularly useful in studying ancient populations, because it is maternally inherited and has a higher mutation rate compared to nuclear DNA. To determine the genetic structure of three Colombian pre-Hispanic populations and compare them with current populations, we determined the haplotypes from human bone remains by sequencing several mitochondrial DNA segments. A wide variety of mitochondrial polymorphisms were obtained from 33 samples. Our results support a high population heterogeneity among pre-Hispanic populations in Colombia.
Potential Founder Variants in COL4A4 Identified in Bukharian Jews Linked to Autosomal Dominant and Autosomal Recessive Alport Syndrome
Authors: Levy Michal , Bazak Lily , Lev-El Noa , Greenberg Rotem , Kropach Nesia , Basel-Salmon Lina , Maya Idit
Published: September 2023

Background: Alport syndrome is a hereditary disorder caused by pathogenic variants in the COL4A gene, which can be inherited in an autosomal recessive, dominant, or X-linked pattern. In the Bukharian Jewish population, no founder pathogenic variant has been reported in COL4A4. Methods: The cohort included 38 patients from 22 Bukharian Jewish families with suspected Alport syndrome who were referred the nephrogenetics clinic between 2012 and 2022. The study collected demographic, clinical, and genetic data from electronic medical records, which were used to evaluate the molecular basis of the disease using Sanger sequencing, and next-generation sequencing. Results: Molecular diagnosis was confirmed in 20/38 patients, with each patient having at least one of the three disease-causing COL4A4 variants detected: c.338GA (p.Gly1008Arg), and c.871-6T>C. In addition, two patients were obligate carriers. Overall, there were 17 heterozygotes, 2 compound heterozygotes, and 3 homozygotes. Each variant was detected in more than one unrelated family. All patients had hematuria with/without proteinuria at referral, and the youngest patient with proteinuria (age 5 years) was homozygous for the c.338G>A variant. End-stage renal disease was diagnosed in two patients at the age of 38 years, a compound heterozygote for c.338G>A and c.871-6T>C. Hearing deterioration was detected in three patients, the youngest aged 40 years, all of whom were heterozygous for c.338G>A. Conclusion: This study unveils three novel disease-causing variants, c.3022G>A, c.871-6T>C, and c.338G>A, in the COL4A4 gene that are recurrent among Jews of Bukharian ancestry, and cause Alport syndrome in both dominant and recessive autosomal inheritance patterns.
Statistical Mechanics Metrics in Pairing and Parsing In Silico and Phenotypic Data of a Novel Genetic NFκB1 (c.T638A) Variant
Authors: Chaudhri Eman N. , Abbott Jessica M. , Islam Naeyma N. , Weber Caleb A. , Coban Mathew A. , Bilgili Ahmet , Squire Jacqueline D. , Mantia Sarah , Wierenga Klaas J. , Caulfield Thomas R.
Published: September 2023

(1) Background: Mutations in NFκB1, a transcriptional regulator of immunomodulating proteins, are a known cause of inborn errors of immunity. Our proband is a 22-year-old male with a diagnosis of common variable immunodeficiency (CVID), cytopenias with massive splenomegaly, and nodular regenerative hyperplasia of the liver. Genetic studies identified a novel, single-point mutation variant in NFκB1, c. T638A p. V213E. (2) Methods: Next-generation panel sequencing of the patient uncovered a novel single-point mutation in the NFκB1 gene that was modeled using the I-TASSER homology-modeling software, and molecular dynamics were assessed using the YASARA2 software (version 20.14.24). (3) Results: This variant replaces valine with glutamic acid at position 213 in the NFκB1 sequence. Molecular modeling and molecular dynamic studies showed altered dynamics in and around the rel homology domain, ankyrin regions, and death domain of the protein. We postulate that these changes alter overall protein function. (4) Conclusions: This case suggests the pathogenicity of a novel variant using protein-modeling techniques and molecular dynamic simulations.
Decoding Cancer Evolution: Integrating Genetic and Non-Genetic Insights
Authors: Ashouri Arghavan , Zhang Chufan , Gaiti Federico
Published: September 2023

The development of cancer begins with cells transitioning from their multicellular nature to a state akin to unicellular organisms. This shift leads to a breakdown in the crucial regulators inherent to multicellularity, resulting in the emergence of diverse cancer cell subpopulations that have enhanced adaptability. The presence of different cell subpopulations within a tumour, known as intratumoural heterogeneity (ITH), poses challenges for cancer treatment. In this review, we delve into the dynamics of the shift from multicellularity to unicellularity during cancer onset and progression. We highlight the role of genetic and non-genetic factors, as well as tumour microenvironment, in promoting ITH and cancer evolution. Additionally, we shed light on the latest advancements in omics technologies that allow for in-depth analysis of tumours at the single-cell level and their spatial organization within the tissue. Obtaining such detailed information is crucial for deepening our understanding of the diverse evolutionary paths of cancer, allowing for the development of effective therapies targeting the key drivers of cancer evolution.