bluuebunny/crossref_metadata_2025 huggingface dataset:
GNSS-Free End-of-Row Detection and Headland Maneuvering for Orchard Navigation Using a Depth Camera
Authors: Peng Chen , Fei Zhenghao , Vougioukas Stavros G.
Published: January 2023

GPS-based navigation in orchards can be unstable because trees may block the GPS signal or introduce multipath errors. Most research on robot navigation without GPS has focused on guidance inside orchard rows; end-of-row detection has not received enough attention. Additionally, navigation between rows relies on reference maps or artificial landmarks. In this work, a novel row-end detection method is presented, which detects drastic changes in the statistical distribution of the sensed point cloud as the robot gets closer to the row’s end. A row-entry method was also implemented that builds a local map that is used by a reactive path tracker. The system was evaluated in a 24-row block in a vineyard. Once the robot was closer than 7 m from the end of a row, the algorithm detected it with a 100% success rate and calculated the distance from it with a mean error of 0.54 m. The system was also evaluated in vineyard configurations with parallel and slanted vine rows in consecutive blocks. The system worked well in all configurations, except where the next block had rows aligned to the rows of the current block and the headland width was closer than 5 m.
Test and Simulation Study on the Static Load and Pure Longitudinal Slip Characteristics of Non-Pneumatic Tire
Authors: Zhu Liangliang , Xu Ting , Liu Xiaoyu , Wu Mengqi , Zhou Xuehan , Gao Fei
Published: January 2023

Compared with pneumatic tires, non-pneumatic tires have incomparable performance, in terms of load bearing and safety. In this paper, the static load characteristics and pure longitudinal slip characteristics of the non-pneumatic tire are studied by combining experiments and simulations. The test results show that the radial stiffness of the original structure is nonlinear, the pure longitudinal sliding characteristics are seriously inconsistent, the brakes are very sensitive, and the driving is slightly soft. A series of designs have been carried out from the aspects of load-bearing mode and anti-symmetry of the structure, and numerical simulations have been carried out. The results show that the radial secant stiffness of the optimized structure II is increased by 58.8%, and the radial tangent stiffness is increased by 2.96 times, under the premise of ensuring the mass reduction. Additionally, the R square is 0.9932, and the linearity of the radial stiffness curve is greatly improved. The braking and driving conditions under pure longitudinal sliding characteristics are more antisymmetric, which greatly improves the braking sensitivity, but the driving performance is not as good as the original structure. In addition, this paper establishes the evaluation index of the non-pneumatic tire carrying mode, which lays the foundation for further exploration of the non-pneumatic tire carrying mechanism.
Spatially Weighted Bayesian Classification of Spatio-Temporal Areal Data Based on Gaussian-Hidden Markov Models
Authors: Dučinskas Kęstutis , Karaliutė Marta , Šaltytė-Vaisiauskė Laura
Published: January 2023

This article is concerned with an original approach to generative classification of spatiotemporal areal (or lattice) data based on implementation of spatial weighting to Hidden Markov Models (HMMs). In the framework of this approach data model at each areal unit is specified by conditionally independent Gaussian observations and first-order Markov chain for labels and call it local HMM. The proposed classification is based on modification of conventional HMM by the implementation of spatially weighted estimators of local HMMs parameters. We focus on classification rules based on Bayes discriminant function (BDF) with plugged in the spatially weighted parameter estimators obtained from the labeled training sample. For each local HMM, the estimators of regression coefficients and variances and two types of transition probabilities are used in two levels (higher and lower) of spatial weighting. The average accuracy rate (ACC) and balanced accuracy rate (BAC), computed from confusion matrices evaluated from a test sample, are used as performance measures of classifiers. The proposed methodology is illustrated for simulated data and for real dataset, i.e., annual death rate data collected by the Institute of Hygiene of the Republic of Lithuania from the 60 municipalities in the period from 2001 to 2019. Critical comparison of proposed classifiers is done. The experimental results showed that classifiers based on HMM with higher level of spatial weighting in majority cases have advantage in spatial–temporal consistency and classification accuracy over one with lower level of spatial weighting.
A Computationally Efficient Distributed Framework for a State Space Adaptive Filter for the Removal of PLI from Cardiac Signals
Authors: Rehman Inam ur , Raza Hasan , Razzaq Nauman , Frnda Jaroslav , Zaidi Tahir , Abbasi Waseem , Anwar Muhammad Shahid
Published: January 2023

The proliferation of cardiac signals, such as high-resolution electrocardiograms (HRECGs), ultra-high-frequency ECGs (UHF–ECGs), and intracardiac electrograms (IEGMs) assist cardiologists in the prognosis of critical cardiac diseases. However, the accuracies of such diagnoses depend on the signal qualities, which are often corrupted by artifacts, such as the power line interference (PLI) and its harmonics. Therefore, state space adaptive filters are applied for the effective removal of PLI and its harmonics. Moreover, the state space adaptive filter does not require any reference signal for the extraction of desired cardiac signals from the observed noisy signal. Nevertheless, the state space adaptive filter inherits high computational complexity; therefore, filtration of the increased number of PLI harmonics bestows an adverse impact on the execution time of the algorithm. In this paper, a parallel distributed framework for the state space least mean square with adoptive memory (PD–SSLMSWAM) is introduced, which runs the computationally expensive SSLMSWAM adaptive filter parallelly. The proposed architecture efficiently removes the PLI along with its harmonics even if the time alignment among the contributing nodes is not the same. Furthermore, the proposed PD-SSLMSWAM scheme provides less computational costs as compared to the sequentially operated SSLMSWAM algorithm. A comparison was drawn among the proposed PD–SSLMSWAM, sequentially operated SSLMSWAM, and state space normalized least mean square (SSNLMS) adaptive filters in terms of qualitative and quantitative performances. The simulation results show that the proposed PD–SSLMSWAM architecture provides almost the same qualitative and quantitative performances as those of the sequentially operated SSLMSWAM algorithm with less computational costs. Moreover, the proposed PD–SSLMSWAM achieves better qualitative and quantitative performances as compared to the SSNLMS adaptive filter.
Double Roman Domination: A Survey
Authors: Rupnik Poklukar Darja , Žerovnik Janez
Published: January 2023

Since 2016, when the first paper of the double Roman domination appeared, the topic has received considerable attention in the literature. We survey known results on double Roman domination and some variations of the double Roman domination, and a list of open questions and conjectures is provided.
An Image-Encipherment Algorithm Using a Combination of a One-Dimensional Chaotic Map and a Three-Dimensional Piecewise Chaotic Map
Authors: Askar Sameh , Alshamrani Ahmad , Elghandour Aesha , Karawia Abdelrahman
Published: January 2023

One-dimensional and three-dimensional piecewise chaotic maps are used to propose an image-encipher technique in this article. First, the logistic map is used to construct the pseudo-random sequence. After that, this sequence is used to scramble the plain image. Next, the three-dimensional piecewise chaotic map has produced a mask of the chaotic sequence. After doing some preprocessing steps on the mask, a bit-wise XOR operation with the mask is applied to the shuffled image. The suggested algorithm is used to encipher and decipher a different range of images. To check the algorithm security and efficiency, the algorithm performance was calculated using multiple statistical tests and compared to several recent algorithms. Furthermore, numerical simulations and experimental data are also used to validate the proposed algorithm’s resistance to various attacks.
Computational Study of Phase Change Heat Transfer and Latent Heat Energy Storage for Thermal Management of Electronic Components Using Neural Networks
Authors: Shafi Jana , Sheremet Mikhail , Fteiti Mehdi , Saeed Abdulkafi Mohammed , Ghalambaz Mohammad
Published: January 2023

The phase change heat transfer of nano-enhanced phase change materials (NePCMs) was addressed in a heatsink filled with copper metal foam fins. The NePCM was made of 1-Tetradecanol graphite nanoplatelets. The heatsink was an annulus contained where its outer surface was subject to a convective cooling of an external flow while its inner surface was exposed to a constant heat flux. The governing equations, including the momentum and heat transfer with phase change, were explained in a partial differential equation form and integrated using the finite element method. An artificial neural network was employed to map the relationship between the anisotropic angle and nanoparticles fractions with the melting volume fraction. The computational model data were used to successfully train the ANN. The trained ANN showed an R-value close to unity, indicating the high prediction accuracy of the neural network. Then, ANN was used to produce maps of melting fractions as a function of design parameters. The impact of the geometrical placement of metal foam fins and concentrations of the nanoparticles on the surface heat transfer was addressed. It was found that spreading the fins (large angles between the fins) could improve the cooling performance of the heatsink without increasing its weight. Moreover, the nanoparticles could reduce the thermal energy storage capacity of the heatsink since they do not contribute to heat transfer. In addition, since the nanoparticles generally increase the surface heat transfer, they could be beneficial only with 1.0% wt in the middle stages of the melting heat transfer.
Comparative Study on the Microstructure and Biodegradation Behavior of Commercialized Pure Mg and Mg-1.0Ca-0.5Sr Alloy in 27 mM HCO3−-SBF: The Influence of the pH Regulation Treatments
Authors: Shafyra Sabri , Nazim Engku Mohammad , Ngadiman Nor Hasrul Akhmal , Sudin Izman
Published: January 2023

The biodegradation behavior of newly developed orthopedic implant materials provides essential insight into the potential degradation products and their ability to match the rate of bone healing prior to complete degradation. Ironically, biodegradation performance is not only influenced by alloy design or advanced surface treatment on the alloy, but also it is dominantly controlled by the specific inorganic species and their concentration in the corrosion media as well as their pH level. In this study, the biodegradation behavior of commercially pure magnesium (CP Mg) and a Mg-1.0Ca-0.5Sr alloy was evaluated in 27 mM HCO3−- Simulated Body Fluid (r-SBF) due to its identical ionic species and concentrations with human blood plasma via immersion test, including (i) hydrogen evolution test (H2), (ii) pH trend, and (iii) weight-loss measurement. To simulate the pH regulation by the physiological homeostatic response, the pseudo-physiological solution was treated with two treatments: through a (i) a 24 h corrosion media renewal routine and through the use of (ii) a TRIS-HCL buffer reagent. The Mg-1.0Ca-0.5Sr alloy is shown to have superior corrosion resistance due to grain refinement and unique secondary phases, whereas the daily renewal routine imparts a better emulation of in vivo corrosion control.
Rickettsia spp. in Ticks of South Luangwa Valley, Eastern Province, Zambia
Authors: Phiri Bruno S. J. , Kattner Simone , Chitimia-Dobler Lidia , Woelfel Silke , Albanus Celina , Dobler Gerhard , Küpper Thomas
Published: January 2023

Ticks are important vectors for Rickettsia spp. belonging to the Spotted Fever Group responsible for causing Rickettsiosis worldwide. Rickettsioses pose an underestimated health risk to tourists and local inhabitants. There is evidence of the presence of Rickettsia spp. in Zambia, however there is limited data. A total of 1465 ticks were collected in 20 different locations from dogs and cattle including one cat. Ticks were identified by morphological features or by sequencing of the 16S mitochondrial rRNA gene. Individual ticks were further tested for rickettsiae using a pan-Rickettsia real-time-PCR. Rickettsia species in PCR-positive ticks were identified by sequencing the 23S-5S intergenic spacer region or partial ompA gene, respectively. Seven tick species belonging to three different tick genera were found, namely: Amblyomma variegatum, Rhipicephalus appendiculatus, Rhipicephalus (Boophilus) microplus, Rhipicephalus simus, Rhipicephalus sanguineus, Rhipicephalus zambesiensis and Haemaphysalis elliptica. Out of the 1465 ticks collected, 67 (4.6%) tested positive in the pan-Rickettsia PCR. This study provides detailed data about the presence of Rickettsia species in South Luangwa Valley, Eastern Province, Zambia for the first time. High prevalence of Rickettsia africae in Amblyomma variegatum was found, which indicates the potential risk of infection in the investigated area. Furthermore, to our best knowledge, this is the first time Rickettsia massiliae, a human pathogen causing spotted fever, has been detected in Zambia.
Microbacterium Cluster EA Bacteriophages: Phylogenomic Relationships and Host Range Predictions
Authors: Milhaven Mark , Versoza Cyril J. , Garg Aman , Cai Lindsey , Cherian Sanjana , Johnson Kamalei , Salas Perez Kevin , Blanco Madison , Lobatos Jackelyn , Mitra Corinne , Strasser Maria , Pfeifer Susanne P.
Published: January 2023

Bacteriophages are being widely harnessed as an alternative to antibiotics due to the global emergence of drug-resistant pathogens. To guide the usage of these bactericidal agents, characterization of their host specificity is vital—however, host range information remains limited for many bacteriophages. This is particularly the case for bacteriophages infecting the Microbacterium genus, despite their importance in agriculture, biomedicine, and biotechnology. Here, we elucidate the phylogenomic relationships between 125 Microbacterium cluster EA bacteriophages—including members from 11 sub-clusters (EA1 to EA11)—and infer their putative host ranges using insights from codon usage bias patterns as well as predictions from both exploratory and confirmatory computational methods. Our computational analyses suggest that cluster EA bacteriophages have a shared infection history across the Microbacterium clade. Interestingly, bacteriophages of all sub-clusters exhibit codon usage preference patterns that resemble those of bacterial strains different from ones used for isolation, suggesting that they might be able to infect additional hosts. Furthermore, host range predictions indicate that certain sub-clusters may be better suited in prospective biotechnological and medical applications such as phage therapy.
Klebsiella pneumoniae Volatile Organic Compounds (VOCs) Protect Artemia salina from Fish Pathogen Aeromonas sp.: A Combined In Vitro, In Vivo, and In Silico Approach
Authors: Mahmud Md. Liton , Islam Shirmin , Biswas Suvro , Mortuza Md. Golam , Paul Gobindo Kumar , Uddin Md. Salah , Akhtar-E-Ekram Md. , Saleh Md. Abu , Zaman Shahriar , Syed Asad , Elgorban Abdallah M. , Zaghloul Nouf S. S.
Published: January 2023

Antibiotic resistance is an alarming threat all over the world, and the biofilm formation efficacy of bacteria is making the situation worse. The antagonistic efficacy of Klebsiella pneumoniae against one of the known fish pathogens, Aeromonas sp., is examined in this study. Moreover, Aeromonas sp.’s biofilm formation ability and in vivo pathogenicity on Artemia salina are also justified here. Firstly, six selected bacterial strains were used to obtain antimicrobial compounds against this pathogenic strain. Among those, Klebsiella pneumoniae, another pathogenic bacterium, surprisingly demonstrated remarkable antagonistic activity against Aeromonas sp. in both in vitro and in vivo assays. The biofilm distrusting potentiality of Klebsiella pneumoniae’s cell-free supernatants (CFSs) was likewise found to be around 56%. Furthermore, the volatile compounds of Klebsiella pneumoniae were identified by GC-MS in order to explore compounds with antibacterial efficacy against Aeromonas sp. through an in silico study, where 5′-methylthioadenosine/S-adenosylhomocysteine nucleosidase (MTAN) (PDB: 5B7P) was chosen as a target protein for its unique characteristics and pathogenicity. Several volatile compounds, such as oxime- methoxy-phenyl-, fluoren-9-ol, 3,6-dimethoxy-9-(2-phenylethynyl)-, and 2H-indol-2-one, 1,3-dihydro- showed a strong binding affinity, with free energy of −6.7, −7.1, and −6.4 Kcal/mol, respectively, in complexes with the protein MTAN. Moreover, the root-mean-square deviation, solvent-accessible surface area, radius of gyration, root-mean-square fluctuations, and hydrogen bonds were used to ensure the binding stability of the docked complexes in the atomistic simulation. Thus, Klebsiella pneumoniae and its potential compounds can be employed as an alternative to antibiotics for aquaculture, demonstrating their effectiveness in suppressing Aeromonas sp.
Gram-Positive Bacteria Cell Wall Peptidoglycan Polymers Activate Human Dendritic Cells to Produce IL-23 and IL-1β and Promote TH17 Cell Differentiation
Authors: Turner Sean , Raisley Brent , Roach Kimberly , Bajaña Sandra , Munroe Melissa E. , James Judith A. , Coggeshall K. Mark , Kovats Susan
Published: January 2023

Gram-positive bacterial infections are a major cause of organ failure and mortality in sepsis. Cell wall peptidoglycan (PGN) is shed during bacterial replication, and Bacillus anthracis PGN promotes a sepsis-like pathology in baboons. Herein, we determined the ability of polymeric Bacillus anthracis PGN free from TLR ligands to shape human dendritic cell (DC) responses that are important for the initiation of T cell immunity. Monocyte-derived DCs from healthy donors were incubated with PGN polymers isolated from Bacillus anthracis and Staphylococcus aureus. PGN activated the human DCs, as judged by the increased expression of surface HLA-DR, CD83, the T cell costimulatory molecules CD40 and CD86, and the chemokine receptor CCR7. PGN elicited the DC production of IL-23, IL-6, and IL-1β but not IL-12p70. The PGN-stimulated DCs induced the differentiation of naïve allogeneic CD4+ T cells into T helper (TH) cells producing IL-17 and IL-21. Notably, the DCs from a subset of donors did not produce significant levels of IL-23 and IL-1β upon PGN stimulation, suggesting that common polymorphisms in immune response genes regulate the PGN response. In sum, purified PGN is a highly stimulatory cell wall component that activates human DCs to secrete proinflammatory cytokines and promote the differentiation of TH17 cells that are important for neutrophil recruitment in extracellular bacterial infections.
QuEChERS-Based Approach to the Extraction of Five Calcium Channel Blockers from Plasma Determined by UPLC-MS/MS
Authors: Zhao Tingting , Jiang Wen , Zhen Xiaolan , Jin Chengcheng , Zhang Yifan , Li Hui
Published: January 2023

Here, a QuEChERS (quick, easy, cheap, effective, rugged, and safe) pretreatment method was combined with UPLC-MS/MS to facilitate the rapid and reliable simultaneous detection of five calcium channel blockers (CCBs) in human plasma. For this approach, samples were treated with 1 mL of acetonitrile, 350 mg of magnesium sulfate, and 70 mg of PSA adsorbent prior to centrifugation. Supernatants then underwent gradient elution for 8 min with an Agilent C18 column using an acetonitrile-water solution supplemented with 5 mmol⋅L−1 of ammonium acetate. This technique exhibited a good linear response in the 1–800 ng⋅mL−1 range for the analyzed drugs, with an R2≥ 0.9921, an accuracy of 87.54–113.05%, a matrix effect (ME) of 91.21–116.39%, a precision of 0.19–11.64%, and stability of no more than 10.05%. This time-saving QuEChERS reagent-based pretreatment technique thus allowed for the simultaneous and accurate detection of five CCBs in human plasma samples, providing a promising new basis for therapeutic drug monitoring in patients with hypertension.
Highly Valuable Fish Oil: Formation Process, Enrichment, Subsequent Utilization, and Storage of Eicosapentaenoic Acid Ethyl Esters
Authors: Yi Mengyuan , You Yue , Zhang Yiren , Wu Gangcheng , Karrar Emad , Zhang Le , Zhang Hui , Jin Qingzhe , Wang Xingguo
Published: January 2023

In recent years, as the demand for precision nutrition is continuously increasing, scientific studies have shown that high-purity eicosapentaenoic acid ethyl ester (EPA-EE) functions more efficiently than mixed omega-3 polyunsaturated fatty acid preparations in diseases such as hyperlipidemia, heart disease, major depression, and heart disease; therefore, the market demand for EPA-EE is growing by the day. In this paper, we attempt to review EPA-EE from a whole-manufacturing-chain perspective. First, the extraction, refining, and ethanolysis processes (fish oil and ethanol undergo transesterification) of EPA-EE are described, emphasizing the potential of green substitute technologies. Then, the method of EPA enrichment is thoroughly detailed, the pros and cons of different methods are compared, and current developments in monomer production techniques are addressed. Finally, a summary of current advanced strategies for dealing with the low oxidative stability and low bioavailability of EPA-EE is presented. In conclusion, understanding the entire production process of EPA-EE will enable us to govern each step from a macro perspective and accomplish the best use of EPA-EE in a more cost-effective and environmentally friendly way.
Chemical Composition, Antioxidant Activity and Cytocompatibility of Polyphenolic Compounds Extracted from Food Industry Apple Waste: Potential in Biomedical Application
Authors: Hobbi Parinaz , Okoro Oseweuba Valentine , Hajiabbas Maryam , Hamidi Masoud , Nie Lei , Megalizzi Véronique , Musonge Paul , Dodi Gianina , Shavandi Amin
Published: January 2023

Apple pomace (AP) from the food industry is a mixture of different fractions containing bioactive polyphenolic compounds. This study provides a systematic approach toward the recovery and evaluation of the physiochemical and biological properties of polyphenolic compounds from AP. We studied subcritical water extraction (SCW) and solvent extraction with ethanol from four different AP fractions of pulp, peel, seed, core, and stem (A), peel (B), seed and core (C), and pulp and peel (D). The subcritical water method at the optimum condition resulted in total polyphenolic compounds (TPC) of 39.08 ± 1.10 mg GAE per g of AP on a dry basis compared to the ethanol extraction with TPC content of 10.78 ± 0.94 mg GAE/g db. Phloridzin, chlorogenic acid, and quercetin were the main identified polyphenolics in the AP fractions using HPLC. DPPH radical scavenging activity of fraction B and subcritical water (SW) extracts showed comparable activity to ascorbic acid while all ethanolic extracts were cytocompatible toward human fibroblast (3T3-L1) and salivary gland acinar cells (NS-SV-AC). Our results indicated that AP is a rich source of polyphenolics with the potential for biomedical applications.
Computational Studies of Auto-Active van der Waals Interaction Molecules on Ultra-Thin Black-Phosphorus Film
Authors: Laref Slimane , Wang Bin , Gao Xin , Gojobori Takashi
Published: January 2023

Using the van der Waals density functional theory, we studied the binding peculiarities of favipiravir (FP) and ebselen (EB) molecules on a monolayer of black phosphorene (BP). We systematically examined the interaction characteristics and thermodynamic properties in a vacuum and a continuum, solvent interface for active drug therapy. These results illustrate that the hybrid molecules are enabled functionalized two-dimensional (2D) complex systems with a vigorous thermostability. We demonstrate in this study that these molecules remain flat on the monolayer BP system and phosphorus atoms are intact. It is inferred that the hybrid FP+EB molecules show larger adsorption energy due to the van der Waals forces and planar electrostatic interactions. The changes in Gibbs free energy at different surface charge fluctuations and temperatures imply that the FP and EB are allowed to adsorb from the gas phase onto the 2D film at high temperatures. Thereby, the results unveiled beneficial inhibitor molecules on two dimensional BP nanocarriers, potentially introducing a modern strategy to enhance the development of advanced materials, biotechnology, and nanomedicine.
Adsorption Kinetic Model Predicts and Improves Reliability of Electrochemical Serotonin Detection
Authors: Chapin Ashley Augustiny , Han Jinjing , Ghodssi Reza
Published: January 2023

Serotonin (5-HT) is a neurotransmitter involved in many biophysiological processes in the brain and in the gastrointestinal tract. Electrochemical methods are commonly used to quantify 5-HT, but their reliability may suffer due to the time-dependent nature of adsorption-limited 5-HT detection, as well as electrode fouling over repeated measurements. Mathematical characterization and modeling of adsorption-based electrochemical signal generation would improve reliability of 5-HT measurement. Here, a model was developed to track 5-HT electrode adsorption and resulting current output by combining Langmuir adsorption kinetic equations and adsorption-limited electrochemical equations. 5-HT adsorption binding parameters were experimentally determined at a carbon-nanotube coated Au electrode: KD = 7 × 10−7 M, kon = 130 M−1 s−1, koff = 9.1 × 10−5 s−1. A computational model of 5-HT adsorption was then constructed, which could effectively predict 5-HT fouling over 50 measurements (R2 = 0.9947), as well as predict electrode responses over varying concentrations and measurement times. The model aided in optimizing the measurement of 5-HT secreted from a model enterochromaffin cell line—RIN14B—minimizing measurement time. The presented model simplified and improved the characterization of 5-HT detection at the selected electrode. This could be applied to many other adsorption-limited electrochemical analytes and electrode types, contributing to the improvement of application-specific modeling and optimization processes.
Epigenetic Regulation of HIV-1 Sense and Antisense Transcription in Response to Latency-Reversing Agents
Authors: Li Rui , Caico Isabella , Xu Ziyan , Iqbal Mohammad Shameel , Romerio Fabio
Published: January 2023

Nucleosomes positioned on the HIV-1 5′ long terminal repeat (LTR) regulate sense transcription as well as the establishment and maintenance of latency. A negative-sense promoter (NSP) in the 3′ LTR expresses antisense transcripts with coding and non-coding activities. Previous studies identified cis-acting elements that modulate NSP activity. Here, we used the two chronically infected T cell lines, ACH-2 and J1.1, to investigate epigenetic regulation of NSP activity. We found that histones H3 and H4 are present on the 3′ LTR in both cell lines. Following treatment with histone deacetylase inhibitors (HDACi), the levels of H3K27Ac increased and histone occupancy declined. HDACi treatment also led to increased levels of RNA polymerase II (RNPII) at NSP, and antisense transcription was induced with similar kinetics and to a similar extent as 5′ LTR-driven sense transcription. We also detected H3K9me2 and H3K27me3 on NSP, along with the enzymes responsible for these epigenetic marks, namely G9a and EZH2, respectively. Treatment with their respective inhibitors had little or no effect on RNPII occupancy at the two LTRs, but it induced both sense and antisense transcription. Moreover, the increased expression of antisense transcripts in response to treatment with a panel of eleven latency-reversing agents closely paralleled and was often greater than the effect on sense transcripts. Thus, HIV-1 sense and antisense RNA expression are both regulated via acetylation and methylation of lysine 9 and 27 on histone H3. Since HIV-1 antisense transcripts act as non-coding RNAs promoting epigenetic silencing of the 5′ LTR, our results suggest that the limited efficacy of latency-reversing agents in the context of ‘shock and kill’ cure strategies may be due to concurrent induction of antisense transcripts thwarting their effect on sense transcription.
Vitamin D Supply of Multivitamins Commercialized Online by Amazon in Western and Southern Europe: A Labeling Analysis
Authors: Ponti Lisa , Gabutti Luca , Faré Pietro B. , Janett Simone , Bianchetti Mario G. , Schulz Peter J. , Lava Sebastiano A. G. , Agostoni Carlo , Milani Gregorio P.
Published: January 2023

Multivitamins are commonly used by the general population, often without medical prescription. The purpose of this report is to inform on the daily vitamin D supply provided by multivitamins containing vitamin D that are commercialized online by Amazon in Western and Southern Europe. We surveyed multivitamins aimed at adults using the following marketplaces: amazon.es®, amazon.de®, amazon.it®, and amazon.fr®. We identified 199 vitamin D3-containing multivitamins sold by Amazon marketplaces: 77 from amazon.es®, 73 from amazon.de®, 33 from amazon.it®, and 16 from amazon.fr®. No multivitamin contained vitamin D2. The daily vitamin D3 supply ranged from 16 to 2000 IU: it was less than 400 IU daily in 108 (54%), 400–800 IU daily in 53 (27%), and more than 800 IU daily in the remaining 38 (19%) products. The vitamin D3 supply of products sold by amazon.it® was on average higher (p < 0.05) than that of products sold by amazon.de®, amazon.fr®, and amazon.es®. In conclusion, the vitamin D supply of multivitamins sold by Amazon may be insufficient, marginally sufficient, or adequate for subjects at high risk of hypovitaminosis D such as subjects 65 years or more of age, pregnant (or lactating) women, or patients on drug treatment or with an underlying disease, where a vitamin D supplementation is advocated.
Prevalence and Characteristics of Australians’ Complementary Medicine Product Use, and Concurrent Use with Prescription and Over-the-Counter Medications—A Cross Sectional Study
Authors: Harnett Joanna , McIntyre Erica , Adams Jon , Addison Tamia , Bannerman Holly , Egelton Lucy , Ma Jessica , Zabakly Leon , Steel Amie
Published: January 2023

Data about the characteristics and prevalence of complementary medicine (CM) product use by Australians, including concurrent use with prescription and over-the-counter medications, have not been collected in the last five years. A cross-sectional online survey involving a representative sample of the Australian population was administered in 2021–2022. Of the 2351 survey responses included in this study, 49.4% reported use of a CM product over the previous 12-month period. Of these, 50% reported they always or often used CM products on the same day as a prescription medicine. Participants aged 65 and over were five times more likely to use CMs and other medications on the same day compared to 18–24-year-olds. Lower levels of education and having a chronic illness were also predictors of same-day use. The prevalence and characteristics of CM use by participants was similar to data collected five years ago. The study shows that concurrent use of CM products with prescription medications among older and more vulnerable populations is prevalent and this area requires further research to help ensure appropriate and safe use of CM products.
Pediatric Overweight, Fatness and Risk for Dyslipidemia Are Related to Diet: A Cross-Sectional Study in 9-year-old Children
Authors: Mascarenhas Paulo , Furtado José M. , Almeida Sílvia M. , Ferraz Maria E. , Ferraz Fernando P. , Oliveira Pedro
Published: January 2023

Pediatric overweight, dyslipidemia and insulin resistance can result from unhealthy lifestyle habits and increase morbidity and mortality in adulthood. Herein, we evaluated the relationship between diet and physical activity patterns with the metabolic health of 9-year-old school children. Measurements included anthropometry, adiposity, lipid, and glycemic profiles. Questionnaires evaluated diet and physical activity. Exploratory factor analysis (EFA) screened for diet patterns, and multilevel models evaluated diet and physical activity patterns against overweight, dyslipidemia, and insulin resistance markers across schools and children. EFA highlighted two diet patterns, Western and Traditional. Food rich in fat, salt, and sugar and fewer vegetables and fruits defined the Western pattern. The Traditional pattern, linked to healthier eating habits, had analogies to the Mediterranean diet. Overall, 39% of the children were overweight (including the obese), while 62% presented cardiovascular risk factors on their lipid profiles. Normal-weight children presented 60% high cholesterol incidence. Global insulin resistance incidence was 4.1%, but almost doubled among the overweight/obese. The Westernized diet consistently linked to worse cardiovascular risk markers, even independently of physical practice. Intensive or competitive physical activity was associated with decreased triglycerides (p = 0.003), regardless of diet. Future prospective studies are warranted to validate these results externally.
Whole Dietary Patterns, Cognitive Decline and Cognitive Disorders: A Systematic Review of Prospective and Intervention Studies
Authors: Townsend Rebecca F. , Logan Danielle , O’Neill Roisin F. , Prinelli Federica , Woodside Jayne V. , McEvoy Claire T.
Published: January 2023

Dementia prevalence is a global public health concern. Adherence towards a healthy dietary pattern (DP) may reduce the risk of cognitive decline and dementia. This narrative systematic review aimed to synthesise prospective and intervention study data to evaluate the impact of a-posteriori and a-priori derived DPs on cognitive ageing, from cognitive decline to incident dementia. Ninety-three studies were included: 83 prospective studies and 10 randomised controlled trials (RCT). Most prospective studies (77%) examined a-priori DPs, with the Mediterranean diet examined most frequently. A total of 52% of prospective and 50% of RCTs reported a protective relationship between ‘healthy’ DPs and global cognitive decline. Overall, 59% of prospective studies reported positive associations between healthy DPs and risk of cognitive disorder. Incident cognitive disorder was examined by only one intervention study (subgroup analysis) which reported a beneficial effect of a low-fat diet on risk of probable dementia in women. Unhealthy DPs were examined less frequently (n = 17; 21%), with 41% of these studies reporting associations between adherence and poorer cognitive outcomes. Overall, there were mixed results for healthy and unhealthy DPs on cognition, likely due to between-study heterogeneity. Standardisation of diet exposure and cognitive outcome measurement would help to reduce this. Future research would benefit from investigating effects of culturally appropriate DPs on individual cognitive domains and incident cognitive disorders in diverse and high-risk populations.
Real-World Analysis of Outcomes and Economic Burden in Patients with Chronic Kidney Disease with and without Secondary Hyperparathyroidism among a Sample of the Italian Population
Authors: Barbuto Simona , Perrone Valentina , Veronesi Chiara , Dovizio Melania , Zappulo Fulvia , Vetrano Daniele , Giannini Sandro , Fusaro Maria , Ancona Domenica Daniela , Barbieri Antonietta , Ferrante Fulvio , Lena Fabio , Palcic Stefano , Re Davide , Rizzi Francesca Vittoria , Cogliati Paolo , Soro Marco , Esposti Luca Degli , Cianciolo Giuseppe
Published: January 2023

This real-world analysis evaluated the clinical and economic burden of non-dialysis-dependent CKD patients with and without secondary hyperparathyroidism (sHPT) in Italy. An observational retrospective study was conducted using administrative databases containing a pool of healthcare entities covering 2.45 million health-assisted individuals. Adult patients with hospitalization discharge diagnoses for CKD stages 3, 4, and 5 were included from 1 January 2012 to 31 March 2015 and stratified using the presence/absence of sHPT. Of the 5710 patients, 3119 were CKD-only (62%) and 1915 were CKD + sHPT (38%). The groups were balanced using Propensity Score Matching (PSM). Kaplan-Meier curves revealed that progression to dialysis and cumulative mortality had a higher incidence in the CKD + sHPT versus CKD-only group in CKD stage 3 patients and the overall population. The total direct healthcare costs/patient at one-year follow-up were significantly higher in CKD + sHPT versus CKD-only patients (EUR 8593 vs. EUR 5671, p < 0.001), mostly burdened by expenses for drugs (EUR 2250 vs. EUR 1537, p < 0.001), hospitalizations (EUR 4628 vs. EUR 3479, p < 0.001), and outpatient services (EUR 1715 vs. EUR 654, p < 0.001). These findings suggest that sHPT, even at an early CKD stage, results in faster progression to dialysis, increased mortality, and higher healthcare expenditures, thus indicating that timely intervention can ameliorate the management of CKD patients affected by sHPT.
Longitudinal Assessment of Serum 25-Hydroxyvitamin D Levels during Pregnancy and Postpartum—Are the Current Recommendations for Supplementation Sufficient?
Authors: Palmrich Pilar , Thajer Alexandra , Schirwani Nawa , Haberl Christina , Zeisler Harald , Ristl Robin , Binder Julia
Published: January 2023

(1) Background: Pregnant women are at risk of vitamin D deficiency. Data on pregnancy outcomes in women with vitamin D deficiency during pregnancy are controversial, and prospective longitudinal data on vitamin D deficiency with consistent definitions in pregnant women are scarce. (2) Methods: The aim of this prospective longitudinal cohort study was to investigate 25-hydroxyvitamin D levels over the course of pregnancy and postpartum in singleton and twin pregnancies with regard to dietary and supplemental vitamin D intake and environmental factors influencing vitamin D levels, evaluated by a standardized food frequency questionnaire. (3) Results: We included 198 healthy singleton and 51 twin pregnancies for analysis. A total of 967 study visits were performed over a 3-year period. Overall, 59.5% of pregnant women were classified as vitamin D deficient in the first trimester, 54.8% in the second trimester, 58.5% in the third trimester, 66.9% at birth, and 60% 12 weeks postpartum, even though 66.4% of the study population reported daily pregnancy vitamin intake containing vitamin D. Dietary vitamin D intake did not affect vitamin D levels significantly. (4) Conclusions: The majority of pregnant women evaluated in this study were vitamin D deficient, despite administration of pregnancy vitamins containing vitamin D. Individualized vitamin D assessment during pregnancy should be considered to ensure adequate supplementation and prevention of hypovitaminosis D.
Evaluation of an Online Learning Concept for Nursing Students in Caring for Patients with Dementia: Results of a Questionnaire Survey
Authors: Dreier-Wolfgramm Adina , Teubner Anja , Kern Katrin
Published: January 2023

Background: Nurses have key roles in caring for patients with dementia. To prepare them for demand-oriented nursing care, there is a need for education. An online course with a focus on healthcare needs assessment was designed. Methods: A quantitative study with a qualitative component using questionnaire-based interviews was implemented. The recruitment of students used the following inclusion criteria: (a) second-year students, and (b) absent from less than three lectures. Overall, n = 48 met the inclusion criteria. Twenty-eight students participated. Quantitative data were analyzed using descriptive statistics. Qualitative data were evaluated using Kuckartz’s content analysis with the software MAXQDA. Results: Nursing students judged the overall course structure as very good (M 1.36, SD 0.48). The learning aims were clearly defined (M 1.61, SD 0.68) and the learning content was adequately demonstrated (M 1.68, SD 0.67). The exercise on geriatric assessment promoted the internal learning process (M 1.67, SD 1.00). The online simulation training made the lectures’ contents easier to understand (M 1.86, SD 0.89). Correlations were determined, among others, between the course structure and the clear definitions of the learning aims (rSp 0.566, p = 0.002). Conclusions: The study describes the feasibility of the online course. To identify the impact on patients’ health and caregivers’ lives, further studies are needed.
Posidonia oceanica (L.) Delile at Its Westernmost Biogeographical Limit (Northwestern Alboran Sea): Meadow Features and Plant Phenology
Authors: Mateo-Ramírez Ángel , Marina Pablo , Martín-Arjona Alejandro , Bañares-España Elena , García Raso José E. , Rueda José L. , Urra Javier
Published: January 2023

Meadows of the seagrass Posidonia oceanica inhabit most infralittoral bottoms of the Mediterranean Sea and are considered one of the main climax stages of the infralittoral environment. This seagrass has its western distributional limit along the coast of the Alboran Sea. Taking into account the decline of P. oceanica meadows and the global scenario of ocean warming, it becomes essential to know the structure, temporal dynamics, sexual reproduction and conservation status of this seagrass, across its geographical distribution, including the distribution boundaries where the meadows withstand limiting environmental conditions. In the present work, we studied the structure, phenology and flowering events of four P. oceanica meadows located in the northwestern Alboran Sea (close to the Strait of Gibraltar). Results indicate a decreasing trend of patch size, bathymetric range and number of leaves per shoot towards the Strait (and the Atlantic Ocean), as well as an increasing trend of shoot density and leaf height. Phenological parameters of the northwestern Alboran Sea P. oceanica meadows presented temporal dynamics similar to meadows from other locations within the biogeographical distribution of this seagrass, with similar or even less annual variability in the former. Although most of the studied P. oceanica meadows seem to present a good health status (BiPo index ~0.6) with high shoot densities and some flowering events, some of them showed evidence of regression.
Cardiovascular Toxicities of Ibrutinib: A Pharmacovigilance Study Based on the United States Food and Drug Administration Adverse Event Reporting System Database
Authors: Zheng Yi , Guo Xiaojing , Chen Chenxin , Chi Lijie , Guo Zhijian , Liang Jizhou , Wei Lianhui , Chen Xiao , Ye Xiaofei , He Jia
Published: January 2023

Background: Although ibrutinib has been widely used to treat haematological malignancies, many studies have reported associated cardiovascular events. These studies were primarily animal experiments and clinical trials. For more rational clinical drug use, a study based on post-marketing data is necessary. Aim: Based on post-marketing data, we investigated the clinical features, time to onset, and outcomes of potential cardiovascular toxicities of ibrutinib. Methods: This disproportionality study utilised data from the 2014–2021 United States Food and Drug Administration Adverse Event Reporting System (FAERS) database. We used two disproportionality methods information component (IC) and reporting odds ratio (ROR)) to detect the potential cardiovascular toxicities of ibrutinib. Positive signals were defined as IC025 > 0 and ROR025 > 1. Results: A total of 10 cardiovascular events showed positive signals: supraventricular tachyarrhythmias, haemorrhagic central nervous system vascular conditions, ventricular tachyarrhythmias, cardiac failure, ischaemic central nervous system vascular conditions, cardiomyopathy, conduction defects, myocardial infarction, myocardial infarction disorders of sinus node function, and torsade de pointes/QT prolongation. Cardiomyopathy and supraventricular tachyarrhythmias were the two most common signals. Disorders of sinus node function were observed for the first time, which may be a new adverse effect of ibrutinib. Conclusions: This pharmacovigilance study systematically explored the adverse cardiovascular events of ibrutinib and provided new safety signals based on past safety information. Attention should be paid to some high-risk signals.
Nano-Based Drug Delivery of Polyphenolic Compounds for Cancer Treatment: Progress, Opportunities, and Challenges
Authors: Jia Wenhui , Zhou Li , Li Lei , Zhou Ping , Shen Zhisen
Published: January 2023

Polyphenols and their derivates, a kind of natural product distributed in herb plants, vegetables, and fruits, are the most abundant antioxidants in the human diet and have been found to display cancer-preventative effects in several epidemiological studies. The scientific community has also validated the anti-cancer bioactivities and low toxicities of polyphenolic compounds, including flavones, tannins, phenolic acids, and anthocyanins, through in vitro and in vivo studies. However, the low stability, weak targeting ability, poor solubility, and low bioavailability of pure polyphenolic agents have significantly impaired their treatment efficacy. Nowadays, nano-based technology has been applied to surmount these restrictions and maximize the treatment efficacy of polyphenols. In this review, we summarize the advantages and related mechanisms of polyphenols in cancer treatment. Moreover, aiming at the poor solubility and low bioavailability of pure polyphenols in vivo, the advantages of nano-based delivery systems and recent research developments are highlighted. Herein, particular emphasis is mainly placed on the most widely used nanomaterials in the delivery of natural products, including liposomes, micelles, and nanogels. Finally, we present an overview and the challenges of future implementations of nano-based delivery systems of polyphenolic compounds in the cancer therapeutic field.
Immune Checkpoint Inhibitors: Changing the Treatment Landscape in Esophagogastric Adenocarcinoma
Authors: Lynch Emer , Duffy Austin G. , Kelly Ronan J.
Published: January 2023

In the West, recent decades have demonstrated an epidemiological trend towards esophago-gastric adenocarcinomas (EGAC), with considerable associated mortality. Historically, chemotherapy has represented the sole systemic treatment option in the advanced EGAC setting, in addition to complementing the role of surgery and radiotherapy in the case of localized disease. Immune checkpoint inhibitors (ICIs) represent a novel systemic therapeutic choice and have revolutionized the management of other malignancies, including melanoma and renal cell carcinomas. This article considers the rationale for ICIs in EGAC, reviews the evidence supporting their role in the current standard of care in EGAC, and briefly considers ongoing trials and future directions for the ICI class in EGAC.