bluuebunny/crossref_metadata_2025 huggingface dataset:
The Magnetic Resonance Imaging Pattern of the Lesions Caused by Knee Overuse in the Pediatric Population
Authors: Djuricic Goran , Milojkovic Djordje , Mijucic Jovana , Ducic Sinisa , Bukva Bojan , Radulovic Marko , Rajovic Nina , Milcanovic Petar , Milic Natasa
Published: August 2022

Background and Objectives: Excessive use of the knee in patients with immature locomotor systems leads to a whole spectrum of morphological changes with possible consequences in adulthood. This study aimed to examine the morphological pattern in magnetic resonance imaging (MRI) that is associated with recurrent pain due to increased physical activity in children. Materials and Methods: This was a retrospective study conducted among pediatric patients treated at the University Children’s Hospital in Belgrade in 2018 and 2019. MRI findings of patients who reported recurrent pain in the knee joint during physical activity and who were without any pathological findings on both clinical examination and knee radiographs were included in the study. Results: MRI findings of 168 patients (73 boys and 95 girls, mean age 14.07 ± 3.34 years) were assessed. Meniscus and cartilage lesions were the most commonly detected morphological findings: meniscus lesions in 49.4%, cartilage ruptures in 44.6%, and cartilage edema in 26.2% of patients. The medial meniscus was more often injured in girls (p = 0.030), while boys were more prone to other joint injuries (p = 0.016), re-injury of the same joint (p = 0.036), bone bruises (p < 0.001), and ligament injuries (p = 0.001). In children older than 15 years, tibial plateau cartilage edema (p = 0.016), chondromalacia patellae (p = 0.005), and retropatellar effusion (p = 0.011) were detected more frequently compared to younger children. Conclusions: Children reporting recurrent knee pain due to increased physical activity, without any detected pathological findings on clinical examination and knee radiography, may have morphological changes that can be detected on MRI. Timely diagnosis of joint lesions should play a significant role in preventing permanent joint dysfunction in the pediatric population as well as in preventing the development of musculoskeletal diseases in adulthood.
Metabolic Profiling of Heliotropium crispum Aerial Parts Using HPLC and FTIR and In Vivo Evaluation of Its Anti-Ulcer Activity Using an Ethanol Induced Acute Gastric Ulcer Model
Authors: Fatima Syeda Farheen , Ishtiaq Saiqa , Lashkar Manar O. , Youssef Fadia S. , Ashour Mohamed L. , Elhady Sameh S.
Published: August 2022

This study explored the antiulcer potential of methanol extract and fractions of Heliotropium crispum roots against the ethanol-induced gastric ulcer model in rats. Metabolic profiling of H. crispum aerial parts using Fourier-transform infrared spectroscopy (FTIR) revealed the presence of different metabolites with various functional groups. Meanwhile, High Performance Liquid Chromatography (HPLC) revealed the presence of three main peaks assigned to myricetin, quercetin, and kaempferol. In vivo, antiulcer activity results showed that the disease control group displayed five tiny ulcers less than 2 mm in diameter in addition to two hemorrhagic streaks. However, in the standard control group, only one small ulcer was visible for the total methanol extract. Gastric tissues and contents were evaluated to determine many parameters such as ulcer score, ulcer index, percentage inhibition of ulcer, gastric pH, gastric juice volume, and acidity. Results were endorsed by histopathological evaluation; gastric pH and mucus content were significantly increased, but gastric juice volume was significantly decreased. All fractions showed a significant decrease in ulcer index and % inhibition except the n-hexane fraction, whose results were insignificant compared to the disease control group. Thus, it was concluded that H. crispum shows an antiulcer effect by decreasing gastric juice volume and acidity, whereas gastric pH and mucus contents were increased that is attributed to the synergistic action of its detected polyphenolic compounds.
Metabolite Identification of HIV-1 Capsid Modulators PF74 and 11L in Human Liver Microsomes
Authors: Xu Shujing , Sun Lin , Ding Dang , Zhang Xujie , Liu Xinyong , Zhan Peng
Published: August 2022

PF74 and 11L, as potent modulators of the HIV-1 capsid protein, have been demonstrated to act at both early and late stages in the HIV-1 life cycle. However, their clearance is high in human liver microsomes (HLMs). The main goal of this study was to clarify the metabolism of PF74 and 11L in HLMs, and provide guidance for future structural optimization. To accomplish this, the phase-I metabolites of PF74 and 11L, resulting from in vitro incubation with HLMs, were investigated via ultra-performance liquid chromatography–ultraviolet–high-resolution mass spectrometry (UPLC–UV–HRMS). The results show that 17 phase-I metabolites were putatively annotated for PF74, whereas 16 phase-I metabolites were found for 11L. The main metabolic pathways of PF74 in HLMs were oxidation and demethylation, and the secondary metabolic pathway was hydrolysis; thus, the di-oxidation and demethylation products (M7, M9, M11, and M14) were found to be major metabolites of PF74 in HLMs. In comparison, the main metabolic pathways of 11L in HLMs were oxidation, demethylation, dehydrogenation, and oxidative deamination, with M6′, M11′, M15′, and M16′ as the main metabolites. We suggest that the indole ring and N-methyl group of PF74, and the aniline group, benzene ring R1′, N-methyl, and methoxy group of 11L, were the main metabolic soft spots. Therefore, our research illuminates structural optimization options in seeking improved HIV-1 CA modulators.
Deterioration in the Quality of Recalcitrant Quercus robur Seeds during Six Months of Storage at Subzero Temperatures: Ineffective Activation of Prosurvival Mechanisms and Evidence of Freezing Stress from an Untargeted Metabolomic Study
Authors: Szuba Agnieszka , Kalemba Ewa Marzena , Wawrzyniak Mikołaj Krzysztof , Suszka Jan , Chmielarz Paweł
Published: August 2022

Pedunculate oak (Quercus robur L.) is an economically important forest-forming species in Poland that produces seeds that are sensitive to desiccation; therefore, short-lived seeds are classified as recalcitrant. Such seeds display active metabolism throughout storage. Acorns stored under controlled conditions (moisture content of 40%, temperature −3 °C) maintain viability for up to 1.5–2 years. Meanwhile, oaks only produce large numbers of seeds every few years during so-called mast years. This results in a scarcity of good-quality seeds for continuous nursery production and restoration. The recalcitrant storage behavior and the requirements of foresters make it necessary to develop a new protocol for longer acorn storage at lower temperatures. Two storage temperatures were tested: −3 °C (currently used in forest practice) and −7 °C. Our results showed that acorns stored for six months exhibited deterioration and reduced germination capacity, as well as reduced seedling performance, particularly when acorns were stored at −7 °C. To elucidate the decrease in quality during storage, an untargeted metabolomics study was performed for the first time and supported with the analysis of carbohydrates and percentages of carbon (C) and nitrogen (N). Embryonic axes were characterized by a lower C:N ratio and higher hydration. A total of 1985 metabolites were detected, and 303 were successfully identified and quantified, revealing 44 known metabolites that displayed significantly up- or downregulated abundance. We demonstrated for the first time that the significant deterioration of seed germination potential, particularly in seeds stored at −7 °C, was accompanied by an increased abundance of phenolic compounds and carbohydrates but also amino acids and phosphorylated monosaccharides, particularly in the embryonic axes. The increased abundance of defense-related metabolites (1,2,4-Benzenetriol; BTO), products of ascorbic acid degradation (threonic and isothreonic acid), as well as antifreezing compounds (sugar alcohols, predominantly threitol), was reported in seed stored at −7 °C. We hypothesize that seed deterioration was caused by freezing stress experienced during six months of storage at −7 °C, a decline in antioxidative potential and the unsuccessful rerouting of the energy-production pathways. Additionally, our data are a good example of the application of high-throughput metabolomic tools in forest management.
Transient Heat Conduction in the Orthotropic Model with Rectangular Heat Source
Authors: He Zeqing , Shi Yingli , Shen Yuqing , Shen Zhigang , Zhang Taihua , Zhao Zhao
Published: August 2022

Epidermal electronic systems (EESs) are a representative achievement for utilizing the full advantages of ultra-thin, stretchable and conformal attachment of flexible electronics, and are extremely suitable for integration with human physiological systems, especially in medical hyperthermia. The stretchable heater with stable electrical characteristics and a uniform temperature field is an irreplaceable core component. The inorganic stretchable heater has the advantage of maintaining stable electrical characteristics under tensile deformation. However, the space between the patterned electrodes that provides tensile properties causes uneven distribution of the temperature field. Aiming at improving the temperature distribution uniformity of stretchable thermotherapy electrodes, an orthotropic heat transfer substrate for stretchable heaters is proposed in this paper. An analytical model for transient heat conduction of stretchable rectangular heaters based on orthotropic transfer characteristics is established, which is validated by finite element analysis (FEA). The homogenization effect of orthotropic heat transfer characteristics on temperature distribution and its evolutionary relationship with time are investigated based on this model. This study will provide beneficial help for the temperature distribution homogenization design of stretchable heaters and the exploration of its transient heat transfer mechanism.
Generation of Multi-Lobe Chua Corsage Memristor and Its Neural Oscillation
Authors: Liu Yue , Li Hui , Guo Shu-Xu , Iu Herbert Ho-Ching
Published: August 2022

The Chua corsage memristor (CCM) is considered as one of the candidates for the realization of biological neuron models due to its rich neuromorphic behaviors. In this paper, a universal model for m-lobe CCM memristor is proposed. Moreover, a novel small-signal equivalent circuit with one capacitor is derived based on the proposed model to determine the edge of chaos and obtain the zero-pole diagrams and analyze the frequency response and oscillation mechanism of the m-lobe CCM system, which are discussed in detail. In view of existence of the edge of chaos, the frequency response and the oscillation mechanism of the simplest oscillator is analysed using the proposed model. Finally, the proposed model has exhibited some essential neural oscillation, including the stable limit cycle, supercritical Hopf bifurcation, spiking and bursting oscillation. This study also reveals a previously undiscovered behavior of bursting oscillation in a CCM system.
Screening of Healthy Feral Pigeons (Columba livia domestica) in the City of Zurich Reveals Continuous Circulation of Pigeon Paramyxovirus-1 and a Serious Threat of Transmission to Domestic Poultry
Authors: Annaheim Désirée , Vogler Barbara Renate , Sigrist Brigitte , Vögtlin Andrea , Hüssy Daniela , Breitler Christian , Hartnack Sonja , Grund Christian , King Jacqueline , Wolfrum Nina , Albini Sarah
Published: August 2022

Pigeon paramyxovirus-1 (PPMV-1) is predominantly isolated from pigeons or doves and forms a separate group of viral strains within Avian Orthoavulavirus-1, the causative agent of Newcastle disease in poultry. Since the introduction of PPMV-1 into Europe in 1981, these strains have rapidly spread all over Europe, and are nowadays considered to be enzootic in feral and hobby pigeons (Columba livia domestica). Infections with PPMV-1 can range from asymptomatic to fatal. To assess whether PPMV-1 continuously circulates in healthy feral pigeons, 396 tissue samples of pigeons from the city of Zurich were tested by reverse transcriptase real-time PCR over the period of one year. PPMV-1-RNA was detected in 41 feral pigeons (10.35%), determined as the dominant European genotype VI.2.1.1.2.2. In 38 of the 41 pigeons where organ samples tested positive, PPMV-1-RNA was also detected in either choana or cloaca swabs. There were no significant differences in positivity rates between seasons, age, and sex. The current study shows that feral pigeons without clinical signs of disease can harbour and most likely excrete PPMV-1. Spill-over into free-range holdings of chickens are therefore possible, as observed in a recent outbreak of Newcastle disease in laying hens due to PPMV-1 genotype VI.2.1.1.2.2. in the canton of Zurich in January 2022.
To Die or Not to Die—Regulated Cell Death and Survival in Cyanobacteria
Authors: Barteneva Natasha S. , Meirkhanova Ayagoz , Malashenkov Dmitry , Vorobjev Ivan A.
Published: August 2022

Regulated cell death (RCD) is central to the development, integrity, and functionality of multicellular organisms. In the last decade, evidence has accumulated that RCD is a universal phenomenon in all life domains. Cyanobacteria are of specific interest due to their importance in aquatic and terrestrial habitats and their role as primary producers in global nutrient cycling. Current knowledge on cyanobacterial RCD is based mainly on biochemical and morphological observations, often by methods directly transferred from vertebrate research and with limited understanding of the molecular genetic basis. However, the metabolism of different cyanobacteria groups relies on photosynthesis and nitrogen fixation, whereas mitochondria are the central executioner of cell death in vertebrates. Moreover, cyanobacteria chosen as biological models in RCD studies are mainly colonial or filamentous multicellular organisms. On the other hand, unicellular cyanobacteria have regulated programs of cellular survival (RCS) such as chlorosis and post-chlorosis resuscitation. The co-existence of different genetically regulated programs in cyanobacterial populations may have been a top engine in life diversification. Development of cyanobacteria-specific methods for identification and characterization of RCD and wider use of single-cell analysis combined with intelligent image-based cell sorting and metagenomics would shed more light on the underlying molecular mechanisms and help us to address the complex colonial interactions during these events. In this review, we focus on the functional implications of RCD in cyanobacterial communities.
Investigating the Physicochemical Property Changes of Plastic Packaging Exposed to UV Irradiation and Different Aqueous Environments
Authors: Conradie Wihann , Dorfling Christie , Chimphango Annie , Booth Andy M. , Sørensen Lisbet , Akdogan Guven
Published: August 2022

A wide range of weathering processes contributes to the degradation of plastic litter items which leads to the formation of microplastics that may be detrimental to marine ecosystems and the organisms inhabiting them. In this study, the impact of UV exposure on the degradation of clear polypropylene (CPP), black polypropylene (BPP), and polyethylene terephthalate (PET) packaging materials was investigated over a period of 6 weeks under dry air conditions representing the terrestrial environment. The exposure was conducted using differently sized and shaped samples at irradiation intensities of 65 W/m2 and 130 W/m2. Results indicated that UV irradiation led to changes in the properties of PET, BPP, and CPP that were proportional to the intensity delivered, leading to a higher level of mass loss, carbonyl indices, crystallinities, and microhardness in all polymer types at 130 W/m2 relative to 65 W/m2. However, material shape and size did not have a significant influence on any property for any of the test materials. Increased mass loss over time was accompanied by considerable increases in carbonyl index (CI) for both PPs. Clear PP (CPP) underwent the most severe degradation, resulting in the highest mass loss, increase in crystallinity, and CI. BPP was less degraded and modified by the UV irradiation than the CPP, indicating that the colorant, carbon black, provided some degree of protection to the bulk polymer material. PET was the least degraded of the three materials, suggesting this polymer type is more resistant to UV degradation. The differences in the degradation behaviours of the three test materials under dry environmental conditions indicate that the UV exposure history of plastic litter might play an important role in its potential for further degradation once it reaches the marine environment. Furthermore, analysis of samples exposed to UV in aqueous media reveals a more irregular set of trends for most material properties measured. Overall, the degree of degradation resulting from UV irradiation in dry environments was more pronounced than in aqueous environments, although the most significant property changes were observed for materials without previous UV exposure histories. Samples with previous UV histories showed higher resistance to further crystallinity changes, which appeared to be due to crosslinking in the pretreatment exposures inhibiting chain alignment into crystalline structures. The effect of solution medium was insignificant, although the presence of water allowed hydrolytic degradation to proceed simultaneously with UV degradation for PET. The reduction of CI in pretreated materials in the aqueous exposures, combined with the mass loss, suggest that the degraded surface layer erodes or products dissolve into surrounding solution medium, leaving a fresh surface of plastic exposed.
Comprehensive Review on Medicinal Applications of Coumarin-Derived Imine–Metal Complexes
Authors: Patil Siddappa A. , Kandathil Vishal , Sobha Anjali , Somappa Sasidhar B. , Feldman Max R. , Bugarin Alejandro , Patil Shivaputra A.
Published: August 2022

Coumarins are fused six-membered oxygen-containing benzoheterocycles that join two synthetically useful rings: α-pyrone and benzene. A survey of the literature shows that coumarins and their metal complexes have received great interest from synthetic chemists, medicinal scientists, and pharmacists due to their wide spectrum of biological applications. For instance, coumarin and its derivatives have been used as precursors to prepare a large variety of medicinal agents. Likewise, coumarin-derived imine–metal complexes have been found to display a variety of therapeutic applications, such as antibacterial, antifungal, anticancer, antioxidant, anthelmintic, pesticidal, and nematocidal activities. This review highlights the current synthetic methodologies and known bioactivities of coumarin-derived imine–metal complexes that make this molecule a more attractive scaffold for the discovery of newer drugs.
Radiopharmaceutical Treatments for Cancer Therapy, Radionuclides Characteristics, Applications, and Challenges
Authors: Salih Suliman , Alkatheeri Ajnas , Alomaim Wijdan , Elliyanti Aisyah
Published: August 2022

Advances in the field of molecular biology have had an impact on biomedical applications, which provide greater hope for both imaging and therapeutics. Work has been intensified on the development of radionuclides and their application in radiopharmaceuticals (RPS) which will certainly influence and expand therapeutic approaches in the future treatment of patients. Alpha or beta particles and Auger electrons are used for therapy purposes, and each has advantages and disadvantages. The radionuclides labeled drug delivery system will deliver the particles to the specific targeting cell. Different radioligands can be chosen to uniquely target molecular receptors or intracellular components, making them suitable for personal patient-tailored therapy in modern cancer therapy management. Advances in nanotechnology have enabled nanoparticle drug delivery systems that can allow for specific multivalent attachment of targeted molecules of antibodies, peptides, or ligands to the surface of nanoparticles for therapy and imaging purposes. This review presents fundamental radionuclide properties with particular reference to tumor biology and receptor characteristic of radiopharmaceutical targeted therapy development.
Identification and Inhibition of the Druggable Allosteric Site of SARS-CoV-2 NSP10/NSP16 Methyltransferase through Computational Approaches
Authors: Faisal Shah , Badshah Syed Lal , Kubra Bibi , Sharaf Mohamed , Emwas Abdul-Hamid , Jaremko Mariusz , Abdalla Mohnad
Published: August 2022

Since its emergence in early 2019, the respiratory infectious virus, SARS-CoV-2, has ravaged the health of millions of people globally and has affected almost every sphere of life. Many efforts are being made to combat the COVID-19 pandemic’s emerging and recurrent waves caused by its evolving and more infectious variants. As a result, novel and unexpected targets for SARS-CoV-2 have been considered for drug discovery. 2′-O-Methyltransferase (nsp10/nsp16) is a significant and appealing target in the SARS-CoV-2 life cycle because it protects viral RNA from the host degradative enzymes via a cap formation process. In this work, we propose prospective allosteric inhibitors that target the allosteric site, SARS-CoV-2 MTase. Four drug libraries containing ~119,483 compounds were screened against the allosteric site of SARS-CoV-2 MTase identified in our research. The identified best compounds exhibited robust molecular interactions and alloscore-score rankings with the allosteric site of SARS-CoV-2 MTase. Moreover, to further assess the dynamic stability of these compounds (CHEMBL2229121, ZINC000009464451, SPECS AK-91811684151, NCI-ID = 715319), a 100 ns molecular dynamics simulation, along with its holo-form, was performed to provide insights on the dynamic nature of these allosteric inhibitors at the allosteric site of the SARS-CoV-2 MTase. Additionally, investigations of MM-GBSA binding free energies revealed a good perspective for these allosteric inhibitor–enzyme complexes, indicating their robust antagonistic action on SARS-CoV-2 (nsp10/nsp16) methyltransferase. We conclude that these allosteric repressive agents should be further evaluated through investigational assessments in order to combat the proliferation of SARS-CoV-2.
Structural Optimization of Graphene Triangular Lattice Phononic Crystal Based on Dissipation Dilution Theory
Authors: Zheng Xiande , Liu Ying , Qiu Jing , Liu Guanjun
Published: August 2022

Nanomechanical resonators offer brilliant mass and force sensitivity applied in many fields, owing to a low mass m and high-quality factor Q. However, in vibrating process, resonant energy is inevitably dissipated. Typically, quality factor does not surpass the inverse of the material loss angle φ. Recently, some exceptions emerged in the use of highly stressed silicon nitride material. As yet, it is interpreted that the pre-stress seems to “dilute” the intrinsic energy dissipation according to the Zener model. Is there any other material that could further break the 1/φ limit and achieve higher quality factors? In our previous research, through theoretical calculation and finite element simulation, we have proved that graphene’s quality factor is two orders of magnitude larger than silicon nitride, on account of the extremely thin thickness of graphene. Based on this, we further optimize the structure of phononic crystals to achieve higher quality factors, in terms of duty cycle and cell size. Through simulation analysis, the quality factor could improve with a larger duty cycle and bigger cell size of triangular lattice phononic crystal. Unexpectedly, the Q amplification coefficient of the 3 × 5-cell structure, which is the least number to compose a phononic crystal with a central defect area, is the highest. In contrast, the minimal cell-number structure in hexagonal lattice could not achieve the brilliant dissipation dilution effect as well as the triangular one. Then we consider how overall size and stress influence quality factor and, furthermore, compare theoretical calculation and finite simulation. Lastly, we start from the primitive 3 × 5 cells, constantly adding cells to the periphery. Through simulation, to our surprise, the largest Q amplification coefficient does not belong to the largest structure, instead originating from the moderate one consisting of 7 × 13 cells.
Vitamin D-Mediated Regulation of Intestinal Calcium Absorption
Authors: Fleet James C.
Published: August 2022

Vitamin D is a critical regulator of calcium and bone homeostasis. While vitamin D has multiple effects on bone and calcium metabolism, the regulation of intestinal calcium (Ca) absorption efficiency is a critical function for vitamin D. This is necessary for optimal bone mineralization during growth, the protection of bone in adults, and the prevention of osteoporosis. Intestinal Ca absorption is regulated by 1,25 dihydroxyvitamin D (1,25(OH)2 D), a hormone that activates gene transcription following binding to the intestinal vitamin D receptor (VDR). When dietary Ca intake is low, Ca absorption follows a vitamin-D-regulated, saturable pathway, but when dietary Ca intake is high, Ca absorption is predominately through a paracellular diffusion pathway. Deletion of genes that mediate vitamin D action (i.e., VDR) or production (CYP27B1) eliminates basal Ca absorption and prevents the adaptation of mice to low-Ca diets. Various physiologic or disease states modify vitamin-D-regulated intestinal absorption of Ca (enhanced during late pregnancy, reduced due to menopause and aging).
Riboflavin (Vitamin B2) Deficiency Induces Apoptosis Mediated by Endoplasmic Reticulum Stress and the CHOP Pathway in HepG2 Cells
Authors: Zhang Bo , Cao Jun-Ting , Wu Yong-Bao , Gao Ke-Xin , Xie Ming , Zhou Zheng-Kui , Tang Jing , Hou Shui-Sheng
Published: August 2022

Riboflavin is an essential micronutrient and a precursor of flavin mononucleotide and flavin adenine dinucleotide for maintaining cell homeostasis. Riboflavin deficiency (RD) induces cell apoptosis. Endoplasmic reticulum (ER) stress is considered to induce apoptosis, and C/EBP homologous protein (CHOP) is a key pathway involved in this process. However, whether RD-induced apoptosis is mediated by ER stress and the CHOP pathway remains unclear and needs further investigation. Therefore, the current study presents the effect of RD on ER stress and apoptosis in the human hepatoma cell line (HepG2). Firstly, cells were cultured in a RD medium (4.55 nM riboflavin) and a control (CON) medium (1005 nM riboflavin). We conducted an observation of cell microstructure characterization and determining apoptosis. Subsequently, 4-phenyl butyric acid (4-PBA), an ER stress inhibitor, was used in HepG2 cells to investigate the role of ER stress in RD-induced apoptosis. Finally, CHOP siRNA was transfected into HepG2 cells to validate whether RD triggered ER stress-mediated apoptosis by the CHOP pathway. The results show that RD inhibited cell proliferation and caused ER stress, as well as increased the expression of ER stress markers (CHOP, 78 kDa glucose-regulated protein, activating transcription factor 6) (p < 0.05). Furthermore, RD increased the cell apoptosis rate, enhanced the expression of proapoptotic markers (B-cell lymphoma 2-associated X, Caspase 3), and decreased the expression of the antiapoptotic marker (B-cell lymphoma 2) (p < 0.05). The 4-PBA treatment and CHOP knockdown markedly alleviated RD-induced cell apoptosis. These results demonstrate that RD induces cell apoptosis by triggering ER stress and the CHOP pathway.
Intermediate Hair Follicles from Patients with Female Pattern Hair Loss Are Associated with Nutrient Insufficiency and a Quiescent Metabolic Phenotype
Authors: Piccini Ilaria , Sousa Marta , Altendorf Sabrina , Jimenez Francisco , Rossi Alfredo , Funk Wolfgang , Bíró Tamás , Paus Ralf , Seibel Jens , Jakobs Mira , Yesilkaya Tanju , Edelkamp Janin , Bertolini Marta
Published: August 2022

Female pattern hair loss (FPHL) is a non-scarring alopecia resulting from the progressive conversion of the terminal (t) scalp hair follicles (HFs) into intermediate/miniaturized (i/m) HFs. Although data supporting nutrient deficiency in FPHL HFs are lacking, therapeutic strategies are often associated with nutritional supplementation. Here, we show by metabolic analysis that selected nutrients important for hair growth such as essential amino acids and vitamins are indeed decreased in affected iHFs compared to tHFs in FPHL scalp skin, confirming nutrient insufficiency. iHFs also displayed a more quiescent metabolic phenotype, as indicated by altered metabolite abundance in freshly collected HFs and release/consumption during organ culture of products/substrates of TCA cycle, aerobic glycolysis, and glutaminolysis. Yet, as assessed by exogenous nutrient supplementation ex vivo, nutrient uptake mechanisms are not impaired in affected FPHL iHFs. Moreover, blood vessel density is not diminished in iHFs versus tHFs, despite differences in tHFs from different FPHL scalp locations or versus healthy scalp or changes in the expression of angiogenesis-associated growth factors. Thus, our data reveal that affected iHFs in FPHL display a relative nutrient insufficiency and dormant metabolism, but are still capable of absorbing nutrients, supporting the potential of nutritional supplementation as an adjunct therapy for FPHL.
Emotional Eating and Perfectionism as Predictors of Symptoms of Binge Eating Disorder: The Role of Perfectionism as a Mediator between Emotional Eating and Body Mass Index
Authors: Bernabéu-Brotóns Elena , Marchena-Giráldez Carlos
Published: August 2022

(1) Background: Perfectionism has been linked to eating disorders and might be a risk factor for the appearance of eating pathologies. The aims of this study are (a) to verify the relationship between perfectionism, emotional eating (EE), binge eating (BE), and body mass index (BMI); (b) to identify the variables that predict BE symptoms and BMI; (c) to study the role of perfectionism as a mediator between EE and BMI. (2) Methods: 312 adult participants answered a cross-sectional survey that included the Multidimensional Perfectionism Scale, the Emotional Eater Questionnaire (EEQ), the Binge Eating Scale (BES), and a sociodemographic questionnaire including BMI. (3) Results: The results suggest a direct correlation between EE, BE, and BMI, showing that EE is a powerful predictor of BE symptoms and BMI. Furthermore, two dimensions of perfectionism have a mediator role between EE and BMI, specifically doubts and actions and concern over mistakes: the presence of these two components of perfectionism reverses the relationship between EE and BMI. (4) Conclusions: These results have significant implications for the understanding of the two different (pathological) eating patterns: intake restriction and overeating and should be considered in intervention programs.
Absent Metabolic Transition from the Early to the Late Period in Non-Survivors Post Cardiac Surgery
Authors: Veraar Cecilia , Fischer Arabella , Bernardi Martin H. , Sulz Isabella , Mouhieddine Mohamed , Dworschak Martin , Tschernko Edda , Lassnigg Andrea , Hiesmayr Michael
Published: August 2022

After major surgery, longitudinal changes in resting energy expenditure (REE) as well as imbalances in oxygen delivery (DO2) and distribution and processing (VO2) may occur due to dynamic metabolic requirements, an impaired macro- and microcirculatory flow and mitochondrial dysfunction. However, the longitudinal pattern of these parameters in critically ill patients who die during hospitalization remains unknown. Therefore, we analyzed in 566 patients who received a pulmonary artery catheter (PAC) their REE, DO2, VO2 and oxygen extraction ratio (O2ER) continuously in survivors and non-survivors over the first 7 days post cardiac surgery, calculated the percent increase in the measured compared with the calculated REE and investigated the impact of a reduced REE on 30-day, 1-year and 6-year mortality in a uni- and multivariate model. Only in survivors was there a statistically significant transition from a negative to a positive energy balance from day 0 until day 1 (Day 0: −3% (−18, 14) to day 1: 5% (−9, 21); p < 0.001). Furthermore, non-survivors had significantly decreased DO2 during the first 4 days and reduced O2ER from day 2 until day 6. Additionally, a lower REE was significantly associated with a worse survival at 30 days, 1 year and 6 years (p = 0.009, p < 0.0001 and p = 0.012, respectively). Non-survivors seemed to be unable to metabolically adapt from the early (previously called the ‘ebb’) phase to the later ‘flow’ phase. DO2 reduction was more pronounced during the first three days whereas O2ER was markedly lower during the following four days, suggesting a switch from a predominantly limited oxygen supply to prolonged mitochondrial dysfunction. The association between a reduced REE and mortality further emphasizes the importance of REE monitoring.
Non-Endemic Leishmaniases Reported Globally in Humans between 2000 and 2021—A Comprehensive Review
Authors: Rocha Rafael , Pereira André , Maia Carla
Published: August 2022

Leishmaniases are human and animal parasitic diseases transmitted by phlebotomine sand flies. Globalization is an important driver of the burden and in the current dynamics of these diseases. A systematic review of articles published between 2000 and 2021 was conducted using the PubMed search engine to identify the epidemiology and clinical management of imported human leishmaniases as a fundamental step to better manage individual cases and traveler and migrant health from a global perspective. A total of 275 articles were selected, representing 10,341 human imported cases. Identified drivers of changing patterns in epidemiology include conflict and war, as well as host factors, such as immunosuppression, natural and iatrogenic. Leishmania species diversity associated with different clinical presentations implies diagnostic and treatment strategies often complex to select and apply, especially in non-endemic settings. Thus, diagnostic and management algorithms for medical clinical decision support are proposed. Increased surveillance of non-endemic cases, whether in vulnerable populations such as refugees/migrants and immunocompromised individuals or travelers, could improve individual health and mitigate the public health risk of introducing Leishmania species into new areas.
Correction: Kumar et al. The Global Emergence of Human Babesiosis. Pathogens 2021, 10, 1447
Authors: Kumar Abhinav , O’Bryan Jane , Krause Peter J.
Published: August 2022

In the original publication [...]
Correction: Belyaeva et al. Tuberculosis and Autoimmunity. Pathophysiology 2022, 29, 298–318
Authors: Belyaeva Irina V. , Kosova Anna N. , Vasiliev Andrei G.
Published: August 2022

The authors would like to make the following correction to the published paper [...]
Neuroprotective Effects of Phytochemicals against Aluminum Chloride-Induced Alzheimer’s Disease through ApoE4/LRP1, Wnt3/β-Catenin/GSK3β, and TLR4/NLRP3 Pathways with Physical and Mental Activities in a Rat Model
Authors: Hamdan Ahmed Mohsen Elsaid , Alharthi Fatimah Hussain J. , Alanazi Ahmed Hadi , El-Emam Soad Z. , Zaghlool Sameh S. , Metwally Kamel , Albalawi Sana Abdulaziz , Abdu Yahia S. , Mansour Reda El-Sayed , Salem Hoda A. , Abd Elmageed Zakaria Y. , Abu-Elfotuh Karema
Published: August 2022

Background: Alzheimer’s disease (AD) is a neurodegenerative disorder that is associated with abnormal cognition. AD is aided in its initiation and progression by hereditary and environmental factors. Aluminum (Al) is a neurotoxic agent that causes oxidative stress, which is linked to AD progression. Additionally, Nrf2/HO-1, APOE4/LRP1, Wnt3/β-catenin, and TLR4/NLRP3 are the main signaling pathways involved in AD pathogenesis. Several phytochemicals are promising options in delaying AD evolution. Objectives: This study aimed at studying the neuroprotective effects of some phytochemicals as morin (MOR), thymol (TML), and thymoquinone (TMQ) on physical and mental activities (PhM) in Al chloride (AlCl3)-induced AD rat model. Another objective was to determine the specificity of phytochemicals to AD signaling pathways using molecular docking. Methods: Eighty male Dawley rats were divided into eight groups. Each group received: saline (control group), AlCl3, (ALAD), PhM, either alone or with a combination of MOR, TML, and/or TMQ for five weeks. Animals were then subjected to behavioral evaluation. Brain tissues were used for histopathological and biochemical analyses to determine the extent of neurodegeneration. The effect of phytochemicals on AlCl3-induced oxidative stress and the main signaling pathways involved in AD progression were also investigated. Results: AlCl3 caused a decline in spatial learning and memory, as well as histopathological changes in the brains of rats. Phytochemicals combined with PhM restored antioxidant activities, increased HO-1 and Nrf2 levels, blocked inflammasome activation, apoptosis, TLR4 expression, amyloide-β generation, and tau hyperphophorylation. They also brought ApoE4 and LRP1 levels back to normal and regulated Wnt3/β-catenin/GSK3β signaling pathway. Conclusions: The use of phytochemicals with PhM is a promising strategy for reducing AD by modulating Nrf2/HO-1, TLR4/NLRP3, APOE4/LRP1, and Wnt3/β-catenin/GSK-3β signaling pathways.
Towards Personalized Allele-Specific Antisense Oligonucleotide Therapies for Toxic Gain-of-Function Neurodegenerative Diseases
Authors: Helm Jacob , Schöls Ludger , Hauser Stefan
Published: August 2022

Antisense oligonucleotides (ASOs) are single-stranded nucleic acid strings that can be used to selectively modify protein synthesis by binding complementary (pre-)mRNA sequences. By specific arrangements of DNA and RNA into a chain of nucleic acids and additional modifications of the backbone, sugar, and base, the specificity and functionality of the designed ASOs can be adjusted. Thereby cellular uptake, toxicity, and nuclease resistance, as well as binding affinity and specificity to its target (pre-)mRNA, can be modified. Several neurodegenerative diseases are caused by autosomal dominant toxic gain-of-function mutations, which lead to toxic protein products driving disease progression. ASOs targeting such mutations—or even more comprehensively, associated variants, such as single nucleotide polymorphisms (SNPs)—promise a selective degradation of the mutant (pre-)mRNA while sparing the wild type allele. By this approach, protein expression from the wild type strand is preserved, and side effects from an unselective knockdown of both alleles can be prevented. This makes allele-specific targeting strategies a focus for future personalized therapies. Here, we provide an overview of current strategies to develop personalized, allele-specific ASO therapies for the treatment of neurodegenerative diseases, such Huntington’s disease (HD) and spinocerebellar ataxia type 3 (SCA3/MJD).
A β–Sitosterol Encapsulated Biocompatible Alginate/Chitosan Polymer Nanocomposite for the Treatment of Breast Cancer
Authors: Afzal Obaid , Akhter Md Habban , Ahmad Irfan , Muzammil Khursheed , Dawria Adam , Zeyaullah Mohammad , Altamimi Abdulmalik S. A. , Khalilullah Habibullah , Mir Najib Ullah Shehla Nasar , Rahman Mohammad Akhlaquer , Ali Abuzer , Shahzad Naiyer , Jaremko Mariusz , Emwas Abdul-Hamid , Abdel Aziz Ibrahim Ibrahim
Published: August 2022

β–sitosterol is the most abundant type of phytosterol or plant sterol and can be found in various plant dietary sources including natural oils, soy products, and nuts. Numerous studies have demonstrated the potential therapeutic and clinical applications of β–sitosterol including lowering low-density lipoprotein and cholesterol levels, scavenging free radicals in the body, and interestingly, treating and preventing cancer. This study focuses on synthesizing and characterizing β–sitosterol encapsulated Alginate/Chitosan nanoparticles (β–sito–Alg/Ch/NPs) and evaluating their effectiveness in breast cancer treatment and their pharmacokinetic profile in vivo. The synthesized NPs, which incurred a mean size of 25 ± 1 nm, were extensively characterized in vitro for various parameters including surface charge and morphology. The NPs were further analyzed using DSC, FT-IR, thermogravimetry and X-ray diffraction studies. The release of β–sito from NPs was carried out in a bio-relevant medium of pH 7.4 and pH 5.5 and samples were drawn off and analyzed under time frames of 0, 8, 16, 32, 64, 48, 80, and 96 h, and the best kinetic release model was developed after fitting drug release data into different kinetic models. The metabolic activity of MCF-7 cells treated with the prepared formulation was assessed. The radical scavenging potential of β–sito–Alg/Ch/NPs was also studied. The pharmacokinetic parameters including Cmax, Tmax, half-life (t1/2), and bioavailability were measured for β–sito–Alg/Ch/NPs as compared to β–sito–suspension. The β–sito–Alg/Ch/NPs stability was assessed at biological pH 7.4. The % drug release in PBS of pH 7.4 reportedly has shown 41 ± 6% vs. 11 ± 1% from β–sito–Alg/Ch/NPs and β–sito–suspension. In acidic pH 5.5 mimicking the tumor microenvironment has shown 75 ± 9% vs. 12 ± 4% drug release from β–sito–Alg/Ch/NPs and β–sito–suspension. When compared to the β–sito–suspension, the β–sito–Alg/Ch/NPs demonstrated greater cytotoxicity (p < 0.05) and ~3.41-fold higher oral bioavailability. Interestingly, this work demonstrated that β–sito–Alg/Ch/NPs showed higher cytotoxicity due to improved bioavailability and antioxidant potential compared to the β–sito–suspension.
Evaluating UK Pharmacy Workers’ Knowledge, Attitudes and Behaviour towards Antimicrobial Stewardship and Assessing the Impact of Training in Community Pharmacy
Authors: Seaton Donna , Ashiru-Oredope Diane , Charlesworth Jordan , Gemmell Isla , Harrison Roger
Published: August 2022

The Antibiotic Guardian (AG) campaign, developed in 2014 is an online ‘pledge’ approach to engage health workers and the public about antimicrobial resistance. It is underpinned by models of science communication and behaviour change. Since its launch until the end of 2021, more than 140,000 individuals pledged. A service evaluation was conducted to determine the impact of the campaign upon UK pharmacy workers, in response to national training introduced in 2020. Pledged pharmacy workers were sent an online questionnaire collating demographics, self-reported behaviour and opportunity to support prudent antibiotic use. It also investigated respondents’ daily practice and antimicrobial stewardship (AMS) efforts, and motivations for pledging. Capability was measured with a set of knowledge questions. Awareness of changes to the Community Pharmacy Quality Scheme in England to include incentivized training on antimicrobial resistance (AMR) was explored. Of the 5344 pharmacy workers invited to participate, 783 (14.6%) responded to the survey. There was a statistically significant difference between job roles and capability score. Pharmacists, including Academic and Hospital Pharmacists and Pharmacy Technicians reported higher confidence and capability scores than Dispensers and Pharmacy Assistants (F = 13.776, p = 0.0002). Respondents reported strong knowledge on antimicrobial resistance and high confidence in fulfilling their AG stewardship pledge within daily practices (92.7% of all respondents answered all capability questions, as measured by knowledge, correctly). Two thirds of respondents (61.6% (423/693)) agreed or strongly agreed that they had access to and were able to utilise local antibiotic prescribing guidance and a similar proportion of responding community pharmacists (60%) were aware of the content of their workplace AMS plans. No statistically significant relationships were found between motivations for pledging and subsequent behaviour; pledging due to mandatory requirements of work-place training was the most common answer in both 2019 (42%) and 2020 (54%) cohorts. This evaluation supports the value of the AG pledge-based approach to engage and educate pharmacy workers. Reflections show its impact on increasing evidence-based stewardship for pharmacy workers and their response to mandatory training requirement by employers highlights the effectiveness of the AG campaign to promote AMS within pharmacy teams.
Research Progress on the Leaf Morphology, Fruit Development and Plant Architecture of the Cucumber
Authors: Li Jie , Cao Jiajian , Wang Chunhua , Hao Ning , Zhang Xiaolan , Liu Mingyue , Wu Tao
Published: August 2022

Cucumber (Cucumis sativus L.) is an annual climbing herb that belongs to the Cucurbitaceae family and is one of the most important economic crops in the world. The breeding of cucumber varieties with excellent agronomic characteristics has gained more attention in recent years. The size and shape of the leaves or fruit and the plant architecture are important agronomic traits that influence crop management and productivity, thus determining the crop yields and consumer preferences. The growth of the plant is precisely regulated by both environmental stimuli and internal signals. Although significant progress has been made in understanding the plant morphological regulation of Arabidopsis, rice, and maize, our understanding of the control mechanisms of the growth and development of cucumber is still limited. This paper reviews the regulation of phytohormones in plant growth and expounds the latest progress in research regarding the genetic regulation pathways in leaf development, fruit size and shape, branching, and plant type in cucumber, so as to provide a theoretical basis for improving cucumber productivity and cultivation efficiency.
Diversity of Molluscan Assemblage in Relation to Biotic and Abiotic Variables in Brown Algal Forests
Authors: Orlando-Bonaca Martina , Trkov Domen , Klun Katja , Pitacco Valentina
Published: August 2022

Canopy-forming macroalgae, mainly those belonging to the order Fucales, form the so-called brown algal forests, which are among the most productive assemblages in shallow coastal zones. Their vertical, branching canopies increase nearshore primary production, provide nursery areas for juvenile fish, and sustain understory assemblages of smaller algae and both sessile and vagile fauna. The majority of benthic invertebrates inhabiting these forests have larval stages that spend some time floating freely or swimming in the plankton. Therefore, canopy-forming macroalgae play an important role as species collectors related to larval supply and hydrodynamic processes. During the past several decades, brown algal forests have significantly reduced their extension and coverage in the Mediterranean basin, due to multiple interacting natural and anthropogenic pressures, with negative consequences also for the related fauna. The aim of this research was to examine how differences in macrophyte abundance and structure, as well as environmental variables, affect the associated molluscan communities in the shallow northern Adriatic Sea. Sampling sites with well-developed vegetation cover dominated by different canopy-forming species were selected in the shallow infralittoral belt of the northern Adriatic Sea in the spring–summer period of the years 2019 and 2020. Our results confirm the importance of algal forests for molluscan assemblage, with a total of 68 taxa of molluscs found associated with macrophytes. Gastropods showed the highest richness and abundance, followed by bivalves. Mollusc richness and diversity (in terms of biotic indices) were not related with the degree of development of canopy-forming species (in terms of total cover and total volume), nor with the ecological status of benthic macroalgae at different depths. On the contrary, the variability in molluscan taxa abundances was explained by some environmental variables, such as temperature, pH, light, and nitrates concentration.