bluuebunny/crossref_metadata_2025 huggingface dataset:
“Mars Bar and a Tin of Red Bull Kept Me and My Patients Alive”: Exploring Barriers to Healthy Eating through Facebook Comments of Shiftworkers
Authors: McIntosh Emma , Ferguson Sally A. , Dorrian Jillian , Coates Alison M. , Leung Gloria , Gupta Charlotte C.
Published: February 2023

The negative impact of an unhealthy diet on the shiftworker population has been well-documented. However, little evidence exists on the underlying reasons for unhealthy eating behaviours and the existing barriers to healthy eating withinshiftwork environments. This qualitative study investigated the dietary behaviours reported by shiftworkers through Facebook comments. Comments were collected if they were on public shiftworker-relevant posts pertaining to dietary news or dietary information on Facebook and were posted by self-identified shiftworkers, relatives of shiftworkers, or partners of shiftworkers. A thematic analysis of the 144 comments collected generated four categories that can be used to understand the motivations for eating behaviour on-shift: what shiftworkers eat, where food is sourced from, when food is eaten, and why certain foods are chosen. Results reveal motivations, attitudes, and both internal and external barriers to healthy eating behaviours, as well as similarities and differences across shiftwork industries. Recommendations for future research include further explorations on the link between scheduled eating (e.g., time-restricted eating) and shiftwork, the impact of a rotating shift arrangements on dietary health behaviours, and the impact of interpersonal relationships on shiftworker dietary choices. Understanding these motivations will inform strategies to promote healthy eating and help understand barriers for shiftworkers.
Arm Circumference, Arm-to-Waist Ratio in Relation to Cardiovascular and All-Cause Mortality among Patients with Diabetes Mellitus
Authors: Xiao Xinyu , Yu Xinyi , Zhu Huiping , Zhai Xiaobing , Li Shiyang , Ma Wenzhi , Ouyang Meishuo , Liu Keyang , Eshak Ehab , Cao Jinhong
Published: February 2023

Among patients with diabetes mellitus, limited studies have investigated the relationship between anthropometric parameters and cardiovascular disease (CVD), with all-cause mortality. We examined the associations of arm circumference (AC), arm-to-waist ratio (AC/WC), and CVD, with all-cause mortality among patients with diabetes. This is a cohort study of 5497 diabetic individuals aged 20 or over who were recruited in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2014. Cox proportional hazards regression models were used to analyze the associations between AC, AC/WC, and CVD, with all-cause mortality. We also conducted stratified analyses and explored the possible non-linear relation by restricted cubic splines. During a median follow-up of 7.2 years, there were 271 and 1093 cases of CVD and all-cause death. The multivariable adjusted hazard ratios (HRs) with 95% confidence intervals (Cis) of CVD mortality in Q2, Q3, and Q4 groups compared with Q1 group were 0.37 (0.22, 0.62), 0.24 (0.12, 0.48), 0.18 (0.07, 0.46) for AC, and 0.18 (0.07, 0.46), 0.34 (0.20, 0.60), 0.28 (0.15, 0.53) for AC/WC. Similar results were observed in the analysis for all-cause mortality risk. AC and AC/WC were both inversely associated with CVD and all-cause mortality among individuals with diabetes. It is important to pay attention to these anthropometric parameters of diabetic patients.
Frequency of Convenience Cooking Product Use Is Associated with Cooking Confidence, Creativity, and Markers of Vegetable Intake
Authors: Brasington Natasha , Bucher Tamara , Beckett Emma L.
Published: February 2023

Low levels of cooking skills, confidence and home cooking are related to poorer dietary outcomes and are a common barrier to adequate vegetable consumption. Convenience cooking products may play a role in lowering the levels of confidence and creativity required to prepare home-cooked meals. It has previously been reported that those who use convenience cooking products have lower levels of cooking confidence and creativity and lower vegetable intakes compared to those who do not use these products. However, the relationship between these outcomes and the frequency of use of convenience cooking products has not been assessed. Therefore, a balanced demographic panel of Australian adults (n = 1034) was surveyed on the frequency of convenience cooking product use, vegetable intake and variety, and opinions and habits regarding vegetable intake. Those who used the products more regularly had higher cooking confidence and creativity, and higher vegetable variety scores, compared to less regular users (p < 0.05). However, the frequency of use of convenience cooking products was not associated with higher vegetable intake and did not influence views around the ease of eating vegetables. Therefore, these products may be a tool for assisting those with lower levels of cooking skills in accessing a higher variety of vegetables, but vegetable quantity in these products may need to be revised to assist consumers in better meeting intake recommendations.
Citrus aurantium ‘Crispifolia’ Essential Oil: A Promise for Nutraceutical Applications
Authors: Di Napoli Michela , Castagliuolo Giusy , Badalamenti Natale , Maresca Viviana , Basile Adriana , Bruno Maurizio , Varcamonti Mario , Zanfardino Anna
Published: February 2023

Food waste is one of the main topics of various scientific studies of the last decade. In this regard, this work analyzed an essential oil (EO) extracted from the flavedo of Citrus aurantium ‘Crispifolia’ fruit. The analysis, performed by GC-MS, showed a chemically variegated chromatogram characterized by the presence of limonene (33.35%), but also by oxygenated monoterpenes such as β-linalool (7.69%), α-terpineol (7.06%), and geranyl acetate (10.12%). EO from the external part of the C. aurantium peel had several properties, including excellent antimicrobial and good antibiofilm activities. It also showed antioxidant activity in vitro and decreased the amount of cellular ROS, thus stimulating the catalytic activity of crucial enzymes involved in mitigating oxidative stress.
High Burden of Co-Infection with Multiple Enteric Pathogens in Children Suffering with Diarrhoea from Rural and Peri-Urban Communities in South Africa
Authors: Potgieter Natasha , Heine Lee , Ngandu Jean Pierre Kabue , Ledwaba Solanka Ellen , Zitha Tinyiko , Mudau Lutendo Sylvia , Becker Piet , Traore Afsatou Ndama , Barnard Tobias George
Published: February 2023

Infectious diarrhoea contributes to high morbidity and mortality in young children from sub-Saharan Africa. The aim of this study was to assess the prevalence of single and multiple diarrhoeal-causing pathogen combinations in children suffering from diarrhoea from rural and peri-urban communities in South Africa. A total of 275 diarrhoea stool specimens were collected between 2014 and 2016 from Hospitals and Primary Health Care clinics. The BioFire® FilmArray® Gastrointestinal panel was used to simultaneously detect 22 diarrhoea pathogens (viruses, bacteria, parasites) known to cause diarrhoea. A total of 82% (226/275) enteric pathogens were detected in the stool specimens. The two most detected bacterial, viral and parasitic pathogens each included: EAEC (42%), EPEC (32%), Adenovirus F40/41 (19%), Norovirus (15%), Giardia (8%) and Cryptosporidium (6%), respectively. Single enteric pathogen infections were recorded in 24% (65/275) specimens with EAEC, and Norovirus was found in 26% (17/65) and 14% (9/65) of the specimens, respectively. Multiple enteric pathogen combinations were recorded in 59% (161/275) of the stool specimens with 53% (85/161) containing two pathogens, 22% (35/161) containing three pathogens and 25% (41/161) containing four or more pathogens. The results from this study demonstrated the complex nature of pathogen co-infections in diarrhoeal episodes which could have an impact on treatment effectiveness.
The Epidemiology of Infectious Diseases Meets AI: A Match Made in Heaven
Authors: Bothra Ankur , Cao Yongguo , Černý Jiří , Arora Gunjan
Published: February 2023

Infectious diseases remain a major threat to public health [...]
Characteristics of Human Babesiosis in Europe
Authors: Hildebrandt Anke , Gray Jeremy , Montero Estrella
Published: February 2023

One of the Editor’s choice articles in 2021 published in Pathogens was a review of human babesiosis in Europe [...]
Insights into Synonymous Codon Usage Bias in Hepatitis C Virus and Its Adaptation to Hosts
Authors: Khandia Rekha , Khan Azmat Ali , Karuvantevida Noushad , Gurjar Pankaj , Rzhepakovsky Igor Vladimirovich , Legaz Isabel
Published: February 2023

Hepatitis C virus (HCV) is enveloped RNA virus, encoding for a polyprotein that is processed by cellular proteases. The virus is responsible for liver cirrhosis, allograft rejection, and human hepatocellular carcinoma. Based on studies including compositional analysis, odds ratio analysis, parity analysis, skew analysis, relative synonymous codon usage, codon bias, and protein properties, it was evident that codon usage bias in HCV is dependent upon the nucleotide composition. Codon context analysis revealed CTC-CTG as a preferred codon pair. While CGA and CGT codons were rare, none of the codons were rare in HCV-like viruses envisaged in the present study. Many of the preferred codon pairs were valine amino acid-initiated, which possibly infers viral infectivity; hence the role of selection forces appears to act on the HCV genome, which was further validated by neutrality analysis where selection accounted for 87.28%, while mutation accounted for 12.72% force shaping codon usage. Furthermore, codon usage was correlated with the length of the genome. HCV viruses prefer valine-initiated codon pairs, while HCV-like viruses prefer alanine-initiated codon pairs. The HCV host range is very narrow and is confined to only humans and chimpanzees. Based on indices including codon usage correlation analysis, similarity index, and relative codon deoptimization index, it is evident in the study that the chimpanzee is the primary host of the virus. The present study helped elucidate the preferred host for HCV. The information presented in the study paved the way for generating an attenuated vaccine candidate through viral recoding, with finely tuned nucleotide composition and a perfect balance of preferred and rare codons.
Electrostatic Adsorption of Dense AuNPs onto Silica Core as High-Performance SERS Tag for Sensitive Immunochromatographic Detection of Streptococcus pneumoniae
Authors: Shen Wanzhu , Li Jiaxuan , Jiang Bo , Nie You , Pang Yuanfeng , Wang Chongwen , Xiao Rui , Hao Rongzhang
Published: February 2023

Streptococcus pneumoniae (S. pneumoniae) is a prominent pathogen of bacterial pneumonia and its rapid and sensitive detection in complex biological samples remains a challenge. Here, we developed a simple but effective immunochromatographic assay (ICA) based on silica-Au core-satellite (SiO2@20Au) SERS tags to sensitively and quantitatively detect S. pneumoniae. The high-performance SiO2@20Au tags with superior stability and SERS activity were prepared by one-step electrostatic adsorption of dense 20 nm AuNPs onto 180 nm SiO2 core and introduced into the ICA method to ensure the high sensitivity and accuracy of the assay. The detection limit of the proposed SERS-ICA reached 46 cells/mL for S. pneumoniae and was 100-fold more sensitive than the traditional AuNPs-based colorimetric ICA method. Further, considering its good stability, specificity, reproducibility, and easy operation, the SiO2@20Au-SERS-ICA developed here has great potential to meet the demands of on-site and accurate detection of respiratory pathogens.
Nanotechnology as a Tool for Optimizing Topical Photoprotective Formulations Containing Buriti Oil (Mauritia flexuosa) and Dry Aloe vera Extracts: Stability and Cytotoxicity Evaluations
Authors: Reis-Mansur Maria Cristina Pinheiro Pereira , Firmino Gomes Christian Campos , Nigro Fiammetta , Ricci-Júnior Eduardo , de Freitas Zaida Maria Faria , dos Santos Elisabete Pereira
Published: February 2023

Human beings are actively exposed to ultraviolet (UV) radiation, which is associated with skin cancer. This has encouraged the continuous search for more effective and safer photoprotective formulations. Along with the application of traditional organic sunscreens, there is a growing interest in “green products” containing natural compounds such as plant extracts and oils. This trend is combined with the use of nanotechnology as a tool for optimizing the vehicles of such compounds. Nanoemulsions (NEs) are suitable for the encapsulation of natural compounds, which improves topical treatment. Therefore, we have developed oil-in-water (O/W) nanoemulsions containing 3% buriti oil (BO), incorporated in a 10% vegetal extract of Aloe vera (AV) by means of ultrasonic processing to improve the chemical characteristics of this component and, consequently, its efficacy and safety in pharmaceutical and cosmetic formulations. The composition of the formulation was initially defined in a preliminary study on surfactants where the concentrations of Tween® 80 and Span® 20 were evaluated in relation to particle size and the polydispersity index (PDI). The nanoemulsion was prepared and then chemical sunscreens were incorporated with the aim of developing a sunscreen nanoemulsion called NE-A19. This nanoemulsion was found to be the best formulation due to its stability, droplet size (146.80 ± 2.74), and PDI (0.302 ± 0.088), with a monomodal size distribution. The stability was evaluated over 90 days and showed a low growth in particle size at the end of the study. NE-A19 exhibited good viscosity and organoleptic properties, in addition to an occlusion factor indicating an interesting and higher water holding capacity when compared with a NE without AV (p < 0.05). The in vitro efficacy and safety studies of NE-19A were promising. Its average in vitro sun protection factor value was 49, with a critical wavelength (λc) of 369.7 nm, satisfactory UVA protection, and a UVA/UVB ratio of 0.40, indicating broad spectrum protection against UVA and UVB radiation. Furthermore, NE-19A displayed a good safety profile in dermal keratinocytes. It can be concluded that NE-19A is a promising formulation for carrying natural products, such as buriti oil and AV, associated with synthetic filters in lower concentrations.
Chemical Constituents, Anticancer and Anti-Proliferative Potential of Limonium Species: A Systematic Review
Authors: Gancedo Naiara Cássia , Isolani Raquel , de Oliveira Natalia Castelhano , Nakamura Celso Vataru , de Medeiros Araújo Daniela Cristina , Sanches Andreia Cristina Conegero , Tonin Fernanda Stumpf , Fernandez-Llimos Fernando , Chierrito Danielly , de Mello João Carlos Palazzo
Published: February 2023

Limonium species represent a source of bioactive compounds that have been widely used in folk medicine. This study aimed to synthesize the anticancer and anti-proliferative potential of Limonium species through a systematic review. Searches were performed in the electronic databases PubMed/MEDLINE, Scopus, and Scielo and via a manual search. In vivo or in vitro studies that evaluated the anticancer or anti-proliferative effect of at least one Limonium species were included. In total, 942 studies were identified, with 33 articles read in full and 17 studies included for qualitative synthesis. Of these, 14 (82.35%) refer to in vitro assays, one (5.88%) was in vivo, and two (11.76%) were designed as in vitro and in vivo assays. Different extracts and isolated compounds from Limonium species were evaluated through cytotoxic analysis against various cancer cells lines (especially hepatocellular carcinoma—HepG2; n = 7, 41.18%). Limonium tetragonum was the most evaluated species. The possible cellular mechanism involved in the anticancer activity of some Limonium species included the inhibition of enzymatic activities and expression of matrix metalloproteinases (MMPs), which suggested anti-metastatic effects, anti-melanogenic activity, cell proliferation inhibition pathways, and antioxidant and immunomodulatory effects. The results reinforce the potential of Limonium species as a source for the discovery and development of new potential cytotoxic and anticancer agents. However, further studies and improvements in experimental designs are needed to better demonstrate the mechanism of action of all of these compounds.
Targeting the IGF-Axis in Cultured Pediatric High-Grade Glioma Cells Inhibits Cell Cycle Progression and Survival
Authors: Chen Yinhsuan Michely , Leibovitch Matthew , Zeinieh Michele , Jabado Nada , Brodt Pnina
Published: February 2023

Pediatric high-grade gliomas (pHGG) accounts for approximately 8–12% of primary brain tumors in children. Prognosis is poor, with a median survival of 9–15 months. Insulin-like growth factor 1-receptor (IGF-1R) gene amplifications have been identified in high-grade gliomas and may contribute to its highly aggressive phenotype, but the effect of IGF inhibitors on pHGG is yet to be determined. In the present study, we analyzed the response of patient-derived pediatric high-grade glioma cells to a novel IGF-1R inhibitor, the IGF-Trap. Using immunohistochemistry, we found that IGF-1R was localized to both the nucleus and cell membrane in different pHGG patient-derived xenograft (PDX) lines under basal conditions. In response to ligand binding, nuclear levels of the receptor increased, and this was associated with the transcriptional upregulation of both the receptor and cyclin D1, suggesting that IGF-1R could regulate its own expression and cell cycle progression in these cells. Insulin-like growth factor-1 (IGF-1) increased the proliferation of the pHGG cells DIPG13 and SGJ2, and this could be blocked by the addition of the IGF-Trap. The IGF-Trap reduced the colony formation of these cells in an optimal growth medium and impeded the ability of IGF-1 to rescue DIPG13 cells from starvation-induced apoptosis. Collectively, these results implicate the IGF-1 axis in the regulation of cell cycle progression, cellular proliferation, and cell survival in pHGG, and identify the IGF-axis as a target and the IGF-Trap as a potential inhibitor of this axis in pHGG.
Quantification of the Chemical Chaperone 4-Phenylbutyric Acid (4-PBA) in Cell Culture Media via LC-HRMS: Applications in Fields of Neurodegeneration and Cancer
Authors: Villani Salvatore , Dematteis Giulia , Tapella Laura , Gagliardi Mara , Lim Dmitry , Corazzari Marco , Aprile Silvio , Del Grosso Erika
Published: February 2023

In recent years, 4-phenylbutyric acid (4-PBA), an FDA-approved drug, has increasingly been used as a nonspecific chemical chaperone in vitro and in vitro, but its pharmacodynamics is still not clear. In this context, we developed and validated a Liquid Chromatography–High Resolution Mass Spectrometry (LC-HRMS) method to quantify 4-PBA in NeuroBasal-A and Dulbecco’s Modified Eagle widely used cell culture media. Samples were injected on a Luna® 3 µm PFP(2) 100 Å (100 × 2.0 mm) column maintained at 40 °C. Water and methanol both with 0.1% formic acid served as mobile phases in a step gradient mode. The mass acquisition was performed by selected ion monitoring (SIM) in negative mode for a total run time of 10.5 min at a flow rate of 0.300 mL/min. The analogue 4-(4-Nitrophenyl)-Butyric Acid served as internal standard. Validation parameters were verified according to FDA and EMA guidelines. The quantification ranges from 0.38–24 µM. Inter and intraday RSDs (Relative Standard Deviations) were within 15%. The developed LC-HRMS method allowed the estimation of 4-PBA absorption and adsorption kinetics in vitro in two experimental systems: (i) 4-PBA improvement of protein synthesis in an Alzheimer’s disease astrocytic cell model; and (ii) 4-PBA reduction of endoplasmic reticulum stress in thapsigargin-treated melanoma cell lines.
Targeting the Endoplasmic Reticulum Stress-Linked PERK/GRP78/CHOP Pathway with Magnesium Sulfate Attenuates Chronic-Restraint-Stress-Induced Depression-like Neuropathology in Rats
Authors: Arab Hany H. , Khames Ali , Alsufyani Shuruq E. , El-Sheikh Azza A. K. , Gad Amany M.
Published: February 2023

Magnesium sulfate has demonstrated marked neuroprotection in eclampsia, hypoxia, stroke, and post-traumatic brain injury rodent models. However, its potential impact against chronic-restraint-stress (CRS)-induced depression-like neuropathology and associated alterations in endoplasmic reticulum (ER) stress have not been adequately examined. The present study aimed to investigate the neuroprotective potential of magnesium sulfate in a rat model of CRS-triggered depression-like behavioral disturbance and the underlying molecular mechanisms. Herein, CRS was induced by placing rats into restraining tubes for 6 h/day for 21 days and the animals were intraperitoneally injected with magnesium sulfate (100 mg/kg/day) during the study period. After stress cessation, the depression-like behavior was examined by the open-field test, sucrose preference test, and forced swimming test. The present data demonstrated that CRS triggered typical depression-like behavioral changes which were confirmed by the Z-normalization scores. Mechanistically, serum circulating corticosterone levels spiked, and the hippocampi of CRS-exposed animals demonstrated a significant decline in serotonin, norepinephrine, and dopamine neurotransmitters. At the molecular level, the hippocampal pro-inflammatory TNF-alpha and IL-1β cytokines and the oxidative stress marker 8-hydroxy-2′-deoxyguanosine (8-HG) increased in stressed animals. In tandem, enhancement of hippocampal ER stress was evidenced by the activation of iNOS/PERK/GRP78/CHOP axis seen by increased protein expression of iNOS, PERK, GRP78, and CHOP signal proteins in the hippocampi of stressed rats. Interestingly, magnesium sulfate administration attenuated the depression-like behavioral outcomes and the histopathological changes in the brain hippocampi. These favorable actions were driven by magnesium sulfate’s counteraction of corticosterone spike, and hippocampal neurotransmitter decline, alongside the attenuation of neuroinflammation, pro-oxidation, and ER stress. In conclusion, the current results suggest the promising neuroprotective/antidepressant actions of magnesium sulfate in CRS by dampening inflammation, ER stress, and the associated PERK/GRP78/CHOP pathway.
Recent Advances in Polymeric Drug Delivery Systems for Peripheral Nerve Regeneration
Authors: Bianchini Marta , Micera Silvestro , Redolfi Riva Eugenio
Published: February 2023

When a traumatic event causes complete denervation, muscle functional recovery is highly compromised. A possible solution to this issue is the implantation of a biodegradable polymeric tubular scaffold, providing a biomimetic environment to support the nerve regeneration process. However, in the case of consistent peripheral nerve damage, the regeneration capabilities are poor. Hence, a crucial challenge in this field is the development of biodegradable micro- nanostructured polymeric carriers for controlled and sustained release of molecules to enhance nerve regeneration. The aim of these systems is to favor the cellular processes that support nerve regeneration to increase the functional recovery outcome. Drug delivery systems (DDSs) are interesting solutions in the nerve regeneration framework, due to the possibility of specifically targeting the active principle within the site of interest, maximizing its therapeutical efficacy. The scope of this review is to highlight the recent advances regarding the study of biodegradable polymeric DDS for nerve regeneration and to discuss their potential to enhance regenerative performance in those clinical scenarios characterized by severe nerve damage.
Effect of Copolymer Properties on the Phase Behavior of Ibuprofen–PLA/PLGA Mixtures
Authors: Iemtsev Anton , Klajmon Martin , Hassouna Fatima , Fulem Michal
Published: February 2023

Prediction of compatibility of the active pharmaceutical ingredient (API) with the polymeric carrier plays an essential role in designing drug delivery systems and estimating their long-term physical stability. A key element in deducing API–polymer compatibility is knowledge of a complete phase diagram, i.e., the solubility of crystalline API in polymer and mutual miscibility of API and polymer. In this work, the phase behavior of ibuprofen (IBU) with different grades of poly(D,L-lactide-co-glycolide) (PLGA) and polylactide (PLA), varying in composition of PLGA and molecular weight of PLGA and PLA, was investigated experimentally using calorimetry and computationally by the perturbed-chain statistical associating fluid theory (PC-SAFT) equation of state (EOS). The phase diagrams constructed based on a PC-SAFT EOS modeling optimized using the solubility data demonstrated low solubility at typical storage temperature (25 °C) and limited miscibility (i.e., presence of the amorphous–amorphous phase separation region) of IBU with all polymers studied. The ability of PC-SAFT EOS to capture the experimentally observed trends in the phase behavior of IBU–PLA/PLGA systems with respect to copolymer composition and molecular weight was thoroughly investigated and evaluated.
Chlorambucil-Loaded Graphene-Oxide-Based Nano-Vesicles for Cancer Therapy
Authors: Kumari Surabhi , Nehra Anuj , Gupta Kshitij , Puri Anu , Kumar Vinay , Singh Krishna Pal , Kumar Mukesh , Sharma Ashutosh
Published: February 2023

In this study, the authors have designed biocompatible nano-vesicles using graphene oxide (GO) for the release of chlorambucil (CHL) drugs targeting cancerous cells. The GO sheets were first sulfonated and conjugated with folic acid (FA) molecules for controlled release and high loading efficiency of CHL. The chlorambucil (CHL) drug loading onto the functionalized GO surface was performed through π-π stacking and hydrophobic interactions with the aromatic planes of GO. The drug loading and “in vitro” release from the nano-vesicles at different pH were studied. The average particle size, absorption, and loading efficiency (%) of FA-conjugated GO sheets (CHL-GO) were observed to be 300 nm, 58%, and 77%, respectively. The drug release study at different pH (i.e., 7.4 and 5.5) showed a slight deceleration at pH 7.4 over pH 5.5. The amount of drug released was very small at pH 7.4 in the first hour which progressively increased to 24% after 8 h. The rate of drug release was faster at pH 5.5; initially, 16% to 27% in the first 3 h, and finally it reached 73% after 9 h. These observations indicate that the drug is released more rapidly at acidic pH with a larger amount of drug-loading ability. The rate of drug release from the CHL-loaded GO was 25% and 75% after 24 h. The biotoxicity study in terms of % cell viability of CHL-free and CHL-loaded GO against human cervical adenocarcinoma cell line was found to have lower cytotoxicity of CHL-loaded nano-vesicles (IC50 = 18 μM) as compared to CHL-free (IC50 = 8 μM). It is concluded that a high drug-loading efficiency and controlled release with excellent biotoxicity of CHL-GO offers an excellent application in the biomedical field.
Fabrication of Stimuli-Responsive Quince/Mucin Co-Poly (Methacrylate) Hydrogel Matrices for the Controlled Delivery of Acyclovir Sodium: Design, Characterization and Toxicity Evaluation
Authors: Aslam Aysha , Ashraf Muhammad Umer , Barkat Kashif , Mahmood Asif , Hussain Muhammad Ajaz , Farid-ul-Haq Muhammad , Lashkar Manar O. , Gad Heba A.
Published: February 2023

Free-radical polymerization technique was adopted to fabricate a stimuli-responsive intelligent quince/mucin co-poly (methacrylate) hydrogel for the controlled delivery of acyclovir sodium. The developed hydrogel matrices were appraised using different parameters, such as drug loading (%), swelling kinetics, pH- and electrolyte-responsive swelling, and sol–gel fraction. Drug-excipient compatibility study, scanning electron microscopy, thermal analysis, powder X-ray diffraction (PXRD) analysis, in vitro drug release studies, drug release kinetics and acute oral toxicity studies were conducted. The results of drug loading revealed an acyclovir sodium loading of 63–75% in different formulations. The hydrogel discs exhibited pH-responsive swelling behavior, showing maximum swelling in a phosphate buffer with a pH of 7.4, but negligible swelling was obvious in an acidic buffer with a pH of 1.2. The swelling kinetics of the developed hydrogel discs exhibited second-order kinetics. Moreover, the hydrogel discs responded to the concentration of electrolytes (CaCl2 and NaCl). The results of the FTIR confirm the formation of the hydrogel via free-radical polymerization. However, the major peaks of acyclovir remain intact, proving drug-excipient compatibility. The results of the SEM analysis reveal the porous, rough surface of the hydrogel discs with multiple cracks and pores over the surface. The results of the PXRD disclose the amorphous nature of the fabricated hydrogel. The dissolution studies showed a minor amount of acyclovir sodium released in an acidic environment, while an extended release up to 36 h in the phosphate buffer was observed. The drug release followed Hixen–Crowell’s kinetics with Fickian diffusion mechanism. The toxicity studies demonstrated the non-toxic nature of the polymeric carrier system. Therefore, these results signify the quince/mucin co-poly (methacrylate) hydrogel as a smart material with the potential to deliver acyclovir into the intestine for an extended period of time.
Cyclodextrin-Calcium Carbonate Micro- to Nano-Particles: Targeting Vaterite Form and Hydrophobic Drug Loading/Release
Authors: Chesneau Cléa , Sow Alpha Oumar , Hamachi Fadila , Michely Laurent , Hamadi Séna , Pires Rémy , Pawlak André , Belbekhouche Sabrina
Published: February 2023

Tailor-made and designed micro- and nanocarriers can bring significant benefits over their traditional macroscopic counterparts in drug delivery applications. For the successful loading and subsequent release of bioactive compounds, carriers should present a high loading capacity, trigger release mechanisms, biodegradability and biocompatibility. Hydrophobic drug molecules can accumulate in fat tissues, resulting in drawbacks for the patient’s recovery. To address these issues, we propose to combine the advantageous features of both host molecules (cyclodextrin) and calcium carbonate (CaCO3) particles in order to load hydrophobic chemicals. Herein, hybrid cyclodextrin-CaCO3 micro- to nano-particles have been fabricated by combining Na2CO3 solution and CaCl2 solution in the presence of an additive, namely poly (vinylsulfonic acid) (PVSA) or glycerol (gly). By investigating experimental parameters and keeping the Na2CO3 and CaCl2 concentrations constant (0.33 M), we have evidenced that the PVSA or gly concentration and mixing time have a direct impact on the final cyclodextrine-CaCO3 particle size. Indeed, by increasing the concentration of PVSA (5 mM to 30 mM) or gly (0.7 mM to 4 mM) or the reaction time (from 10 min to 4 h), particles with a size of 200 nm could be reached. Interestingly, the vaterite or calcite form could also be selected, according to the experimental conditions. We hypothesised that the incorporation of PVSA or gly into the precipitation reaction might reduce the nucleation rate by sequestering Ca2+. The obtained particles have been found to keep their crystal structure and surface charge after storage in aqueous media for at least 6 months. In the context of improving the therapeutic benefit of hydrophobic drugs, the developed particles were used to load the hydrophobic drug tocopherol acetate. The resulting particles are biocompatible and highly stable in a physiological environment (pH 7.4, 0.15 M NaCl). A selective release of the cargo is observed in acidic media (pH lower than 5).
In Silico Studies to Support Vaccine Development
Authors: Saldanha Leonor , Langel Ülo , Vale Nuno
Published: February 2023

The progress that has been made in computer science positioned in silico studies as an important and well-recognized methodology in the drug discovery and development process. It has numerous advantages in terms of costs and also plays a huge impact on the way the research is conducted since it can limit the use of animal models leading to more sustainable research. Currently, human trials are already being partly replaced by in silico trials. EMA and FDA are both endorsing these studies and have been providing webinars and guidance to support them. For instance, PBPK modeling studies are being used to gather data on drug interactions with other drugs and are also being used to support clinical and regulatory requirements for the pediatric population, pregnant women, and personalized medicine. This trend evokes the need to understand the role of in silico studies in vaccines, considering the importance that these products achieved during the pandemic and their promising hope in oncology. Vaccines are safer than other current oncology treatments. There is a huge variety of strategies for developing a cancer vaccine, and some of the points that should be considered when designing the vaccine technology are the following: delivery platforms (peptides, lipid-based carriers, polymers, dendritic cells, viral vectors, etc.), adjuvants (to boost and promote inflammation at the delivery site, facilitating immune cell recruitment and activation), choice of the targeted antigen, the timing of vaccination, the manipulation of the tumor environment, and the combination with other treatments that might cause additive or even synergistic anti-tumor effects. These and many other points should be put together to outline the best vaccine design. The aim of this article is to perform a review and comprehensive analysis of the role of in silico studies to support the development of and design of vaccines in the field of oncology and infectious diseases. The authors intend to perform a literature review of all the studies that have been conducted so far in preparing in silico models and methods to support the development of vaccines. From this point, it was possible to conclude that there are few in silico studies on vaccines. Despite this, an overview of how the existing work could support the design of vaccines is described.
Potential Drug-Related Problems in Pediatric Patients—Describing the Use of a Clinical Decision Support System at Pharmacies in Sweden
Authors: Abdulkadir Sazan Abass , Wettermark Björn , Hammar Tora
Published: February 2023

The clinical support system Electronic Expert Support (EES) is available at all pharmacies in Sweden to examine electronic prescriptions when dispensing to prevent drug-related problems (DRPs). DRPs are common, and result in patient suffering and substantial costs for society. The aim of this research was to study the use of EES for the pediatric population (ages 0–12 years), by describing what types of alerts are generated for potential DRPs, how they are handled, and how the use of EES has changed over time. Data on the number and categories of EES analyses, alerts, and resolved alerts were provided by the Swedish eHealth Agency. The study shows that the use of EES has increased. The most common type of alert for a potential DRP among pediatric patients was regarding high doses in children (30.3% of all alerts generated). The most common type of alert for a potential DRP that was resolved among pediatrics was therapy duplication (4.6% of the alerts were resolved). The most common reason for closing an alert was dialogue with patient for verification of the treatment (66.3% of all closed alerts). Knowledge of which type of alerts are the most common may contribute to increased prescriber awareness of important potential DRPs.
A Data Processing and Distribution System Based on Apache NiFi
Authors: Wnęk Karol , Boryło Piotr
Published: February 2023

The monitoring of physical and logical networks is essential for the high availability of 5G/6G networks. This could become a challenge in 5G/6G deployments due to the heterogeneity of the optical layer. It uses equipment from multiple vendors, and, as a result, the protocols and methods for gathering monitoring data usually differ. Simultaneously, to effectively support 5G/6G networks, the optical infrastructure should also be dense and ensure high throughput. Thus, vast numbers of photonic transceivers operating at up to 400 Gbps are needed to interconnect network components. In demanding optical solutions for 5G and beyond, enterprise-class equipment will be used—for example, high-capacity and high-density optical switches based on the SONiC distribution. These emerging devices produce vast amounts of data on the operational parameters of each optical transceiver, which should be effectively collected, processed, and analyzed. The aforementioned circumstances may lead to the necessity of using multiple independent monitoring systems dedicated to specific optical hardware. Apache NiFi can be used to address these potential issues. Its high configurability enables the aggregation of unstandardized log files collected from heterogenous devices. Furthermore, it is possible to configure Apache NiFi to absorb huge data streams about each of the thousands of transceivers comprising high-density optical switches. In this way, data can be preprocessed by using Apache NiFi and later uploaded to a dedicated system. In this paper, we focus on presenting the tool, its capabilities, and how it scales horizontally. The proven scalability is essential for making it usable in optical networks that support 5G/6G networks. Finally, we propose a unique optimization process that can greatly improve the performance and make Apache NiFi suitable for high-throughput and high-density photonic devices and optical networks. We also present some insider information on real-life implementations of Apache NiFi in commercial 5G networks that fully rely on optical networks.
Willow (Salix babylonica) Extracts Can Act as Biostimulants for Enhancing Salinity Tolerance of Maize Grown in Soilless Culture
Authors: Mutlu-Durak Hande , Arikan Yagmur , Kutman Bahar Yildiz
Published: February 2023

Salinity negatively affects agricultural production by reducing crop growth and yield. Botanical biostimulants can be used as innovative and sustainable tools to cope with abiotic stress. In this study, salicylic acid (SA) (25 µM) and willow leaf (WL) (0.1 and 0.2%) and bark (WB) (0.1 and 0.2%) extracts were applied as plant-based biostimulants to hydroponically grown maize in the absence and presence of salinity stress (60 mM NaCl). The hormone-like activity and mineral composition of willow extracts were analyzed, and the effects of willow extracts on growth parameters, chlorophyll content, antioxidative enzyme activities, protein levels and mineral nutrient concentrations of maize plants were measured. Within the tested biostimulant applications, 0.2% WB, 0.1% WL and 0.2% WL gave the most promising results, considering the stress alleviating effects. The shoot biomass was increased up to 50% with 0.1% WL treatment and Na+ uptake was reduced with biostimulant applications under saline conditions. Under stress, the protein concentrations of maize leaves were enhanced by 50% and 80% with high doses of WB and WL applications, respectively. Results indicate that willow tree prunings can be valuable bio-economy resources, and aqueous extracts prepared from their leaves and barks can be used as effective and eco-friendly biostimulants.
Selection and Validation of Reference Genes for RT-qPCR Analysis of Gene Expression in Nicotiana benthamiana upon Single Infections by 11 Positive-Sense Single-Stranded RNA Viruses from Four Genera
Authors: Zhang Ge , Zhang Zhuo , Wan Qionglian , Zhou Huijie , Jiao Mengting , Zheng Hongying , Lu Yuwen , Rao Shaofei , Wu Guanwei , Chen Jianping , Yan Fei , Peng Jiejun , Wu Jian
Published: February 2023

Quantitative real-time PCR (RT-qPCR) is a widely used method for studying alterations in gene expression upon infections caused by diverse pathogens such as viruses. Positive-sense single-stranded (ss(+)) RNA viruses form a major part of all known plant viruses, and some of them are damaging pathogens of agriculturally important crops. Analysis of gene expression following infection by ss(+) RNA viruses is crucial for the identification of potential anti-viral factors. However, viral infections are known to globally affect gene expression and therefore selection and validation of reference genes for RT-qPCR is particularly important. In this study, the expression of commonly used reference genes for RT-qPCR was studied in Nicotiana benthamiana following single infection by 11 ss(+) RNA viruses, including five tobamoviruses, four potyviruses, one potexvirus and one polerovirus. Stability of gene expression was analyzed in parallel by four commonly used algorithms: geNorm, NormFinder, BestKeeper, and Delta CT, and RefFinder was finally used to summarize all the data. The most stably expressed reference genes differed significantly among the viruses, even when those viruses were from the same genus. Our study highlights the importance of the selection and validation of reference genes upon different viral infections.
On the Prospects of In Situ Conservation of Medicinal- and Aromatic-Plant Genetic Resources at Ancient-Hillfort Sites: A Case Study from Lithuania
Authors: Labokas Juozas , Karpavičienė Birutė
Published: February 2023

Twenty-three ancient-hillfort sites were investigated to evaluate the potential for the in situ conservation of medicinal- and aromatic-plant populations. An evaluation of the site’s suitability was carried out by employing three major groups of criteria: species-specific, site-specific, and threat assessment. The species-specific criteria included the total species number, target species number, the cover-abundance of the target species estimated by mean Braun–Blanquet score, and, as an additional criterion, the number and cover-abundance of crop wild relatives. The site-specific criteria included site evaluation with respect to climatic region, the area size of a site, the habitat type, and the site’s protection status. The threat assessment was focused on anthropogenic activities, such as recreational, agricultural, and others. The total number of vascular plant species inventoried was 264, including 82 species of medicinal and aromatic plants (MAP). There was a strong and highly significant correlation between the total and the MAP species numbers (rs = 0.77, p < 0.001), and the two most species-rich sites, Žuklijai and Pamiškė, contained the highest total and MAP species numbers. The investigated hillfort sites covered the populations of 49 species, or about 33% of the priority species list, with 5 or more populations. The most frequent species, Hypericum perforatum, occurred at 21 sites. The twenty-three hillfort sites represent three of the four climatic regions and six of the ten climatic subregions of Lithuania. Although these hillfort sites are quite small (1.24 ± 0.75 ha on average, without buffer zone), they are scattered across the country and are state-protected as archaeological objects, which makes them suitable for the in situ conservation of MAP genetic resources. In addition, seven hillfort sites (30.4% of the investigated ones) belong to the European network of special areas of conservation of habitats (Natura 2000), thus increasing their international importance. The threat assessment showed that anthropogenic activities (recreational, agricultural, etc.) are among the major factors affecting target-species populations.
Characterization of Leaf Rust Resistance in International Barley Germplasm Using Genome-Wide Association Studies
Authors: Ziems Laura A. , Singh Lovepreet , Dracatos Peter M. , Dieters Mark J. , Sanchez-Garcia Miguel , Amri Ahmed , Verma Ramesh Pal Singh , Park Robert F. , Singh Davinder
Published: February 2023

A panel of 114 genetically diverse barley lines were assessed in the greenhouse and field for resistance to the pathogen Puccinia hordei, the causal agent of barley leaf rust. Multi-pathotype tests revealed that 16.6% of the lines carried the all-stage resistance (ASR) gene Rph3, followed by Rph2 (4.4%), Rph1 (1.7%), Rph12 (1.7%) or Rph19 (1.7%). Five lines (4.4%) were postulated to carry the gene combinations Rph2+9.am, Rph2+19 and Rph8+19. Three lines (2.6%) were postulated to carry Rph15 based on seedling rust tests and genotyping with a marker linked closely to this gene. Based on greenhouse seedling tests and adult-plant field tests, 84 genotypes (73.7%) were identified as carrying APR, and genotyping with molecular markers linked closely to three known APR genes (Rph20, Rph23 and Rph24) revealed that 48 of the 84 genotypes (57.1%) likely carry novel (uncharacterized) sources of APR. Seven lines were found to carry known APR gene combinations (Rph20+Rph23, Rph23+Rph24 and Rph20+Rph24), and these lines had higher levels of field resistance compared to those carrying each of these three APR genes singly. GWAS identified 12 putative QTLs; strongly associated markers located on chromosomes 1H, 2H, 3H, 5H and 7H. Of these, the QTL on chromosome 7H had the largest effect on resistance response to P. hordei. Overall, these studies detected several potentially novel genomic regions associated with resistance. The findings provide useful information for breeders to support the utilization of these sources of resistance to diversify resistance to leaf rust in barley and increase resistance durability.
First Report on the Genetic Diversity of Populations of Gossypium barbadense L. and Gossypium hirsutun L. in the Amazonian Native Communities, Cusco-Peru
Authors: Morales-Aranibar Luis , Yucra Francisca Elena Yucra , Aranibar Carlos Genaro Morales , Sáenz Manuel Canto , Gonzales Hebert Hernán Soto , Aguilera Jorge González , Álvarez Juan Luis Lazo , Zuffo Alan Mario , Steiner Fabio , Ratke Rafael Felippe , Teodoro Paulo Eduardo
Published: February 2023

The genus Gossypium has important ethnobotanical and economic value for Amazonian Native Communities (A.N.C.). However, little research has been undertaken on the distribution and genetic diversity of cotton populations maintained in the Peruvian rainforest. This work aims to present the first report on the genetic diversity of Gossypium spp. populations in the A.N.C. of the province of La Convención, Cusco-Peru. The methodology was based on exploring, collecting, identifying, and characterizing the Gossypium populations present in the A.N.C. Twenty-six descriptors were evaluated (9 quantitative and 17 qualitative), and with this information, distribution, correlation, and principal component (PC) analyses were carried out. As a result, plants of two species [G. barbadense L. (44 samples) and G. hirsutum L. (19 samples)], one variety [G. barbadense var. brasiliensis (75 samples)], and three previously unidentified variations (9 samples) were identified. Altogether, 147 samples were collected. G. barbadense var. brasiliensis, which was always found in association with other economic crops within an altitude range of 338 to 1086 m, was the most predominant (51%), distributed in eleven A.N.C. and always in small plots (up to 2 ha). G. barbadense L. was cultivated between 397 and 1137 m of altitude in eight A.N.C. in plots of up to 3 ha in marginal lands. G. hirsutum L., with a smaller distribution (13%), was found between 334 and 497 m of altitude in only three communities; this species is cultivated in marginal areas throughout the year. The variability found for the first two PCs when considering the quantitative and qualitative descriptors was high (74.7%) and moderate (48.2%), respectively. When combining all the descriptors, the analysis showed that the first two PCs accounted for 51.8% of the total variability of the data. The PCs of the two types of data and their combination confirmed that the three populations found were grouped. The nine undefined samples were close to or intermediate between the described ones, showing that these samples may be the result of spontaneous crosses; as such, these samples need to be better evaluated with other tools for further definition. The information obtained shows that in the A.N.C. of Cusco-Peru, there is variability conserved by the inhabitants, who have been able to maintain and use these genotypes, even from their Amazonian indigenous ancestry, and the environment has been able to generate variability among the species, as will be highlighted in future works.