bluuebunny/crossref_metadata_2025 huggingface dataset:
Formation of Copper Oxide Nanotextures on Porous Calcium Carbonate Templates for Water Treatment
Authors: Diab Mahmud , Shreteh Karam , Volokh Michael , Mokari Taleb
Published: October 2021

The necessity of providing clean water sources increases the demand to develop catalytic systems for water treatment. Good pollutants adsorbers are a key ingredient, and CuO is one of the candidate materials for this task. Among the different approaches for CuO synthesis, precipitation out of aqueous solutions is a leading candidate due to the facile synthesis, high yield, sustainability, and the reported shape control by adjustment of the counter anions. We harness this effect to investigate the formation of copper oxide-based 3D structures. Specifically, the counter anion (chloride, nitrate, and acetate) affects the formation of copper-based hydroxides and the final structure following their conversion into copper oxide nanostructures over porous templates. The formation of a 3D structure is obtained when copper chloride or nitrate reacts with a Sorites scaffold (marine-based calcium carbonate template) without external hydroxide addition. The transformation into copper oxides occurs after calcination or reduction of the obtained Cu2(OH)3X (X = Cl− or NO3−) while preserving the porous morphology. Finally, the formed Sorites@CuO structure is examined for water treatment to remove heavy metal cations and degrade organic contaminant molecules.
Comparing Dimerization Free Energies and Binding Modes of Small Aromatic Molecules with Different Force Fields
Authors: Patmanidis Ilias , Alessandri Riccardo , de Vries Alex H. , Marrink Siewert J.
Published: October 2021

Dimerization free energies are fundamental quantities that describe the strength of interaction of different molecules. Obtaining accurate experimental values for small molecules and disentangling the conformations that contribute most to the binding can be extremely difficult, due to the size of the systems and the small energy differences. In many cases, one has to resort to computational methods to calculate such properties. In this work, we used molecular dynamics simulations in conjunction with metadynamics to calculate the free energy of dimerization of small aromatic rings, and compared three models from popular online servers for atomistic force fields, namely G54a7, CHARMM36 and OPLS. We show that, regardless of the force field, the profiles for the dimerization free energy of these compounds are very similar. However, significant care needs to be taken when studying larger molecules, since the deviations from the trends increase with the size of the molecules, resulting in force field dependent preferred stacking modes; for example, in the cases of pyrene and tetracene. Our results provide a useful background study for using topology builders to model systems which rely on stacking of aromatic moieties, and are relevant in areas ranging from drug design to supramolecular assembly.
How to Make a Cocktail of Palladium Catalysts with Cola and Alcohol: Heteroatom Doping vs. Nanoscale Morphology of Carbon Supports
Authors: Pentsak Evgeniy O. , Galushko Alexey S. , Cherepanova Vera A. , Ananikov Valentine P.
Published: October 2021

Sparkling drinks such as cola can be considered an affordable and inexpensive starting material consisting of carbohydrates and sulfur- and nitrogen-containing organic substances in phosphoric acid, which makes them an excellent precursor for the production of heteroatom-doped carbon materials. In this study, heteroatom-doped carbon materials were successfully prepared in a quick and simple manner using direct carbonization of regular cola and diet cola. The low content of carbon in diet cola allowed reaching a higher level of phosphorus in the prepared carbon material, as well as obtaining additional doping with nitrogen and sulfur due to the presence of sweeteners and caffeine. Effects of carbon support doping with phosphorus, nitrogen and sulfur, as well as of changes in textural properties by ball milling, on the catalytic activity of palladium catalysts were investigated in the Suzuki–Miyaura and Mizoroki–Heck reactions. Contributions of the heteroatom doping and specific surface area of the carbon supports to the increased activity of supported catalysts were discussed. Additionally, the possibility of these reactions to proceed in 40% potable ethanol was studied. Moreover, transformation of various palladium particles (complexes and nanoparticles) in the reaction medium was detected by mass spectrometry and transmission electron microscopy, which evidenced the formation of a cocktail of catalysts in a commercial 40% ethanol/water solution.
The New Standardized Malaysian Healthy Eating Index
Authors: Jailani Marhamah , Elias Siti Masitah , Rajikan Roslee
Published: October 2021

Healthy Eating Index (HEI) is a diet quality measure that assesses the population’s compliance towards dietary guidelines. In Malaysia, diet quality measure, though existing, has some limitations in terms of application and relevance. This study aims to develop a new standardized Malaysian Healthy Eating Index (S-MHEI) that can measure the diet quality of all Malaysians regardless of their energy requirement level. The Malaysian Dietary Guidelines (MDG) 2010 and MDG for Children and Adolescents (MDGCA) 2013 were used as main references in developing the index components. In addition, the latest Malaysian Adults Nutrition Survey (MANS) and Adolescent Nutrition Survey (ANS) were also referred to ensure the relevance of the components selected. For adequacy components, the least restrictive method was used in setting the standard for the scoring system. Meanwhile, the scoring system for moderation components was built based on the Recommended Nutrient Intake (RNI) 2017. The new S-MHEI comprises of 11 components with a maximum total score of 100. The least restrictive method allowed the index to be used across energy requirement levels. However, the index will not be sensitive towards adhering to the specific recommended amount of intake—which in effect, made the index focus on measuring diet quality rather than diet quantity.
Time-Restricted Eating: A Novel and Simple Dietary Intervention for Primary and Secondary Prevention of Breast Cancer and Cardiovascular Disease
Authors: Christensen Rebecca A. G. , Kirkham Amy A.
Published: October 2021

There is substantial overlap in risk factors for the pathogenesis and progression of breast cancer (BC) and cardiovascular disease (CVD), including obesity, metabolic disturbances, and chronic inflammation. These unifying features remain prevalent after a BC diagnosis and are exacerbated by BC treatment, resulting in elevated CVD risk among survivors. Thus, therapies that target these risk factors or mechanisms are likely to be effective for the prevention or progression of both conditions. In this narrative review, we propose time-restricted eating (TRE) as a simple lifestyle therapy to address many upstream causative factors associated with both BC and CVD. TRE is simple dietary strategy that typically involves the consumption of ad libitum energy intake within 8 h, followed by a 16-h fast. We describe the feasibility and safety of TRE and the available evidence for the impact of TRE on metabolic, cardiovascular, and cancer-specific health benefits. We also highlight potential solutions for overcoming barriers to adoption and adherence and areas requiring future research. In composite, we make the case for the use of TRE as a novel, safe, and feasible intervention for primary and secondary BC prevention, as well as tertiary prevention as it relates to CVD in BC survivors.
Sensitivity of Food-Based Recommendations Developed Using Linear Programming to Model Input Data in Young Kenyan Children
Authors: Borgonjen-van den Berg Karin J. , de Vries Jeanne H. M. , Chopera Prosper , Feskens Edith J. M. , Brouwer Inge D.
Published: October 2021

Food-based recommendations (FBR) developed using linear programming generally use dietary intake and energy and nutrient requirement data. It is still unknown to what extent the availability and selection of these data affect the developed FBR and identified problem nutrients. We used 24 h dietary recalls of 62 Kenyan children (4–6 years of age) to analyse the sensitivity of the FBR and problem nutrients to (1) dietary intake data, (2) selection criteria applied to these data and (3) energy and nutrient requirement data, using linear programming (Optifood©), by comparing a reference scenario with eight alternative scenarios. Replacing reported by estimated consumption frequencies increased the recommended frequencies in the FBR for most food groups while folate was no longer identified as a problem nutrient. Using the 10–90th instead of the 5–95th percentile of distribution to define minimum and maximum frequencies/week decreased the recommended frequencies in the FBR and doubled the number of problem nutrients. Other alternative scenarios negligibly affected the FBR and identified problem nutrients. Our study shows the importance of consumption frequencies for developing FBR and identifying problem nutrients by linear programming. We recommend that reported consumption frequencies and the 5–95th percentiles of distribution of reported frequencies be used to define the minimum and maximum frequencies.
Intermittent Fasting and Sleep: A Review of Human Trials
Authors: McStay Mara , Gabel Kelsey , Cienfuegos Sofia , Ezpeleta Mark , Lin Shuhao , Varady Krista A.
Published: October 2021

This review examines the effects of two popular intermittent fasting regimens on sleep in adults with overweight and obesity. Specifically, the effects of time restricted eating (TRE; eating all food within a 4–10 h window) and alternate day fasting (ADF; 600 kcal fast day alternated with ad libitum feast day) on sleep quality, sleep duration, sleep latency, sleep efficiency, insomnia severity, and risk of obstructive sleep apnea, will be summarized. The role of weight loss will also be discussed. Results from our review reveal that the majority of these trials produced weight loss in the range of 1–6% from baseline. Sleep quality and sleep duration remained unaltered with TRE and ADF, as assessed by the Pittsburgh Sleep Quality Index (PSQI). The effects of intermittent fasting on sleep latency and sleep efficiency are mixed, with one study showing worsening of these parameters, and others showing no effect. Insomnia severity and the risk of obstructive sleep apnea remained unchanged in the trials assessing these metrics. Taken together, these preliminary findings suggest that TRE and ADF produce mild to moderate weight loss (1–6%) but their effects on sleep remain unclear. Solid conclusions are difficult to establish since participants in the studies had healthy sleep durations and no clinical insomnia at baseline, leaving little room for improvement in these metrics. Moreover, none of the trials were adequately powered to detect statistically significant changes in any measure of sleep. Future well-powered trials, conducted in individuals with diagnosed sleep disturbances, will be necessary to elucidate the effect of these popular diets on sleep.
Associations of Food and Nutrient Intake with Serum Hepcidin and the Risk of Gestational Iron-Deficiency Anemia among Pregnant Women: A Population-Based Study
Authors: Mayasari Noor Rohmah , Bai Chyi-Huey , Hu Tzu-Yu , Chao Jane C.-J. , Chen Yi Chun , Huang Ya Li , Wang Fan-Fen , Tinkov Alexey A. , Skalny Anatoly V. , Chang Jung-Su
Published: October 2021

Hepcidin is a regulator of iron metabolism. Diet affects the body’s iron status, but how it influences hepcidin concentrations and the risk of gestational iron-deficiency anemia (IDA) remains unclear. We investigated relationships of food and nutrient intake with serum hepcidin levels in relation to the iron status at a population scale. A retrospective cross-sectional study was conducted based on data obtained from the Nationwide Nutrition and Health Survey in pregnant women, Taiwan (2017~2020). In total, 1430 pregnant women aged 20~45 years with a singleton pregnancy were included. Data from blood biochemistry, 24-h dietary recall, and a food frequency questionnaire were collected during a prenatal checkup. Adjusted multivariate linear and logistic regression analyses were employed to measure the beta coefficient (ß) and 95% confidence interval (CI) of serum hepcidin and the odds ratio (OR) of IDA. In IDA women, serum hepcidin levels were positively correlated with the intake frequency of Chinese dim sum and related foods (β = 0.037 (95% CI = 0.015~0.058), p = 0.001) and dark leafy vegetables (β = 0.013 (0.001~0.025), p = 0.040), but they were negatively correlated with noodles and related products (β = −0.022 (−0.043~−0.001), p = 0.038). An adjusted multivariate logistic regression analysis showed that dietary protein [OR: 0.990 (0.981~1.000), p = 0.041], total fiber [OR: 0.975 (0.953~0.998), p = 0.031], and rice/rice porridge [OR: 1.007 (1.00~1.014), p = 0.041] predicted gestational IDA. Total carbohydrates [OR: 1.003 (1.000~1.006), p = 0.036], proteins [OR: 0.992 (0.985~0.999), p = 0.028], gourds/shoots/root vegetables [OR: 1.007 (0.092~1.010), p = 0.005], and to a lesser extent, savory and sweet glutinous rice products [OR: 0.069 (0.937~1.002), p = 0.067] and dark leafy vegetables [OR: 1.005 (0.999~1.011), p = 0.088] predicted IDA. The risk of IDA due to vegetable consumption decreased with an increasing vitamin C intake (p for trend = 0.024). Carbohydrates and vegetables may affect the gestational iron status through influencing hepcidin levels. Vitamin C may lower the risk of gestational IDA due to high vegetable consumption.
Free-Living Dietary Intake in Tactical Personnel and Implications for Nutrition Practice: A Systematic Review
Authors: MacKenzie-Shalders Kristen L. , Tsoi Angela V. , Lee Ka Wing , Wright Charlene , Cox Gregory R. , Orr Robin M.
Published: October 2021

Tactical personnel (including military, law enforcement, and fire and rescue) are responsible for ensuring national and public safety. Dietary intake is an important consideration to support optimal health and performance. The aims of this systematic review were to: (1) describe the reported free-living dietary intake (energy and macronutrients) of tactical personnel, and (2) describe the practical implications of reported dietary intakes to support the physical and dietary requirements of tactical personnel. A systematic search of databases (MEDLINE, EMBASE, CINAHL and Web of Science) was conducted following the PRISMA guidelines. English and full text research articles were identified and screened against inclusion and exclusion criteria. Demographic and dietary intake data were extracted, tabulated, and synthesized narratively. The quality of the studies was assessed using the Academy of Nutrition and Dietetics Quality Criteria Checklist. Twenty-two studies (15 military, 4 law enforcement, and 2 fire and rescue) were eligible to inform this review. The volume of evidence suggested that tactical personnel met dietary protein and exceeded dietary fat recommendations but failed to meet energy and carbohydrate recommendations. Therefore, practical approaches to support optimized energy, fat and carbohydrate intake in tactical personnel is important.
A Community-Based Approach to Integrating Socio, Cultural and Environmental Contexts in the Development of a Food Database for Indigenous and Rural Populations: The Case of the Batwa and Bakiga in South-Western Uganda
Authors: Scarpa Giulia , Berrang-Ford Lea , Twesigomwe Sabastian , Kakwangire Paul , Peters Remco , Zavaleta-Cortijo Carol , Patterson Kaitlin , Namanya Didacus B. , Lwasa Shuaib , Nowembabazi Ester , Kesande Charity , Harris-Fry Helen , Cade Janet E.
Published: October 2021

Comprehensive food lists and databases are a critical input for programs aiming to alleviate undernutrition. However, standard methods for developing them may produce databases that are irrelevant for marginalised groups where nutritional needs are highest. Our study provides a method for identifying critical contextual information required to build relevant food lists for Indigenous populations. For our study, we used mixed-methods study design with a community-based approach. Between July and October 2019, we interviewed 74 participants among Batwa and Bakiga communities in south-western Uganda. We conducted focus groups discussions (FGDs), individual dietary surveys and markets and shops assessment. Locally validated information on foods consumed among Indigenous populations can provide results that differ from foods listed in the national food composition tables; in fact, the construction of food lists is influenced by multiple factors such as food culture and meaning of food, environmental changes, dietary transition, and social context. Without using a community-based approach to understanding socio-environmental contexts, we would have missed 33 commonly consumed recipes and foods, and we would not have known the variety of ingredients’ quantity in each recipe, and traditional foraged foods. The food culture, food systems and nutrition of Indigenous and vulnerable communities are unique, and need to be considered when developing food lists.
Influence of Tilia tomentosa Moench Extract on Mouse Small Intestine Neuromuscular Contractility
Authors: Cerantola Silvia , Faggin Sofia , Annaloro Gabriela , Mainente Federica , Filippini Raffaella , Savarino Edoardo Vincenzo , Piovan Anna , Zoccatelli Gianni , Giron Maria Cecilia
Published: October 2021

Functional gastrointestinal disorders (FGIDs) are characterized by abdominal pain, bloating and bowel disturbances. FGID therapy is primarily symptomatic, including treatment with herbal remedies. Flower extract of Tilia tomentosa Moench (TtM) is occasionally used as an anti-spasmodic in popular medicine. Since its effect on intestinal response is unknown, we evaluated the influence of TtM extract on small intestine contractility. Ileal preparations from C57BL/6J mice were mounted in organ baths to assess changes in muscle tension, following addition of TtM extract (0.5–36 μg/mL) or a vehicle (ethanol). Changes in contractile response to receptor- and non-receptor-mediated stimuli were assessed in ileal preparations pretreated with 12 μg/mL TtM. Alterations in the enteric nervous system neuroglial network were analyzed by confocal immunofluorescence. Increasing addition of TtM induced a marked relaxation in ileal specimens compared to the vehicle. Pretreatment with TtM affected cholinergic and tachykininergic neuromuscular contractions as well as K+-induced smooth muscle depolarization. Following incubation with TtM, a significant reduction in non-adrenergic non-cholinergic-mediated relaxation sensitive to Nω-Nitro-L-arginine methyl ester hydrochloride (pan-nitric oxide synthase inhibitor) was found. In vitro incubation of intestinal specimens with TtM did not affect the myenteric plexus neuroglial network. Our findings show that TtM-induced intestinal relaxation is mediated by nitric oxide pathways, providing a pharmacological basis for the use of TtM in FGIDs.
Indole-3-Propionic Acid, a Gut-Derived Tryptophan Metabolite, Associates with Hepatic Fibrosis
Authors: Sehgal Ratika , Ilha Mariana , Vaittinen Maija , Kaminska Dorota , Männistö Ville , Kärjä Vesa , Tuomainen Marjo , Hanhineva Kati , Romeo Stefano , Pajukanta Päivi , Pihlajamäki Jussi , de Mello Vanessa D.
Published: October 2021

Background and Aims: Gut microbiota-derived metabolites play a vital role in maintenance of human health and progression of disorders, including obesity and type 2 diabetes (T2D). Indole-3-propionic acid (IPA), a gut-derived tryptophan metabolite, has been recently shown to be lower in individuals with obesity and T2D. IPA’s beneficial effect on liver health has been also explored in rodent and cell models. In this study, we investigated the association of IPA with human liver histology and transcriptomics, and the potential of IPA to reduce hepatic stellate cell activation in vitro. Methods: A total of 233 subjects (72% women; age 48.3 ± 9.3 years; BMI 43.1 ± 5.4 kg/m2) undergoing bariatric surgery with detailed liver histology were included. Circulating IPA levels were measured using LC-MS and liver transcriptomics with total RNA-sequencing. LX-2 cells were used to study hepatoprotective effect of IPA in cells activated by TGF-β1. Results: Circulating IPA levels were found to be lower in individuals with liver fibrosis compared to those without fibrosis (p = 0.039 for all participants; p = 0.013 for 153 individuals without T2D). Accordingly, levels of circulating IPA associated with expression of 278 liver transcripts (p < 0.01) that were enriched for the genes regulating hepatic stellate cells (HSCs) activation and hepatic fibrosis signaling. Our results suggest that IPA may have hepatoprotective potential because it is able to reduce cell adhesion, cell migration and mRNA gene expression of classical markers of HSCs activation in LX-2 cells (all p < 0.05). Conclusion: The association of circulating IPA with liver fibrosis and the ability of IPA to reduce activation of LX-2 cells suggests that IPA may have a therapeutic potential. Further molecular studies are needed to investigate the mechanisms how IPA can ameliorate hepatic fibrosis.
Vitamin D Status and Physical Activity during Wintertime in Forensic Inpatients—A Randomized Clinical Trial
Authors: Hansen Anita L. , Ambroziak Gina , Thornton David M. , Mundt James C. , Kahn Rachel E. , Dahl Lisbeth , Waage Leif , Kattenbraker Daniel , Grung Bjørn
Published: October 2021

This study aimed to gain deeper knowledge about the relationship between vitamin D and physical activity in a sample of forensic inpatients. Sixty-seven male forensic inpatients participated. Participants were randomly assigned into an Intervention group (vitamin D) or a Control group (placebo). The Physical Activity–Rating (PA-R) questionnaire was used to measure physical activity from January to May. Vitamin D status was measured as 25-hydroxy vitamin D (25-OHD) pre- and post-intervention. The results revealed that vitamin D status at post-test was positively correlated with physical activity, but there was no effect of vitamin D supplementation looking at the two randomized groups. However, controlling for body mass index (BMI), the results showed an effect of BMI and a main effect of groups with a higher level of physical activity in the Intervention group. No interaction effects were found. Participants were also assigned into High and Low vitamin D groups based on the vitamin D status at post-test; i.e., the upper (75.1 nmol/L) and lower quartile (46.7 nmol/L). T-tests revealed that participants with a vitamin D status above 75 nmol/L showed significantly higher levels of physical activity than participants with a vitamin D status below 46.7 nmol/L. Thus, a vitamin D status above 75 nmol/L seems to be an optimal level.
I Believe It Is Healthy—Impact of Extrinsic Product Attributes in Demonstrating Healthiness of Functional Food Products
Authors: Plasek Brigitta , Lakner Zoltán , Temesi Ágoston
Published: October 2021

Due to the high proportion of impulse purchases and the short time devoted to purchase decisions, packaging and other extrinsic attributes are becoming increasingly important in demonstrating the health benefits of a functional food item to consumers as plausibly as possible. Our research aims at identifying the role of extrinsic features (claims related to ingredients and health claims, organic or domestic origin, as well as the shape and color of packaging), gathered in the course of in-depth literature analysis, in the case of a functional smoothie. Our online consumer questionnaire was completed by 633 respondents, and the answers were assessed by choice based conjoint analysis. Our results show that each examined attribute plays a role in the assessment of health effects. The color blue has the biggest impact on making the consumer believe in the health benefits of the product. This is followed by the indication of organic origin, then the statement emphasizing the natural quality of the ingredients. The assessment of the specific extrinsic attributes is affected by consumers’ general health interest level, their involvement with food items, and their various demographic features.
Strategies to Improve School Meal Consumption: A Systematic Review
Authors: Cohen Juliana F. W. , Hecht Amelie A. , Hager Erin R. , Turner Lindsey , Burkholder Kara , Schwartz Marlene B.
Published: October 2021

School meals can play an integral role in improving children’s diets and addressing health disparities. Initiatives and policies to increase consumption have the potential to ensure students benefit from the healthy school foods available. This systematic review evaluates studies examining initiatives, interventions, and policies to increase school meal consumption. Following PRISMA guidelines, this review was conducted using four databases and resulted in a total of 96 studies. The research evidence supports the following strategies to increase school meal consumption: (1) offering students more menu choices; (2) adapting recipes to improve the palatability and/or cultural appropriateness of foods; (3) providing pre-sliced fruits; (4) rewarding students who try fruits and vegetables; (5) enabling students to have sufficient time to eat with longer (~30 min) lunch periods; (6) having recess before lunch; and (7) limiting students’ access to competitive foods during the school day. Research findings were mixed when examining the impact of nutrition education and/or offering taste tests to students, although multiple benefits for nutrition education outside the cafeteria were documented. There is some evidence that choice architecture (i.e., “Smarter Lunchroom”) techniques increase the proportion of students who select targeted meal components; however, there is not evidence that these techniques alone increase consumption. There were limited studies of the impact of increasing portion sizes; serving vegetables before other meal components; and strengthening local district and/or school wellness policies, suggesting that further research is necessary. Additionally, longer-term studies are needed to understand the impact of policies that limit students’ access to flavored milk. Several studies found increases in students’ meal consumption following the Healthy Hunger-Free Kids Act (HHFKA) and concerns regarding an increase in food waste following the HHFKA were not supported. Overall, there are a range of effective strategies to increase school meal consumption that can be implemented by schools, districts, and policymakers at the local, state, and federal levels (PROSPERO registration: CRD42021244688).
The Rapid Assessment of Aggregated Wastewater Samples for Genomic Surveillance of SARS-CoV-2 on a City-Wide Scale
Authors: Rouchka Eric C. , Chariker Julia H. , Saurabh Kumar , Waigel Sabine , Zacharias Wolfgang , Zhang Mei , Talley Daymond , Santisteban Ian , Puccio Madeline , Moyer Sarah , Holm Rochelle H. , Yeager Ray A. , Sokoloski Kevin J. , Fuqua Joshua , Bhatnagar Aruni , Smith Ted
Published: October 2021

Throughout the course of the ongoing SARS-CoV-2 pandemic there has been a need for approaches that enable rapid monitoring of public health using an unbiased and minimally invasive means. A major way this has been accomplished is through the regular assessment of wastewater samples by qRT-PCR to detect the prevalence of viral nucleic acid with respect to time and location. Further expansion of SARS-CoV-2 wastewater monitoring efforts to include the detection of variants of interest/concern through next-generation sequencing has enhanced the understanding of the SARS-CoV-2 outbreak. In this report, we detail the results of a collaborative effort between public health and metropolitan wastewater management authorities and the University of Louisville to monitor the SARS-CoV-2 pandemic through the monitoring of aggregate wastewater samples over a period of 28 weeks. Through the use of next-generation sequencing approaches the polymorphism signatures of Variants of Concern/Interest were evaluated to determine the likelihood of their prevalence within the community on the basis of their relative dominance within sequence datasets. Our data indicate that wastewater monitoring of water quality treatment centers and smaller neighborhood-scale catchment areas is a viable means by which the prevalence and genetic variation of SARS-CoV-2 within a metropolitan community of approximately one million individuals may be monitored, as our efforts detected the introduction and emergence of variants of concern in the city of Louisville. Importantly, these efforts confirm that regional emergence and spread of variants of interest/concern may be detected as readily in aggregate wastewater samples as compared to the individual wastewater sheds. Furthermore, the information gained from these efforts enabled targeted public health efforts including increased outreach to at-risk communities and the deployment of mobile or community-focused vaccination campaigns.
Tracking the Transcription Kinetic of SARS-CoV-2 in Human Cells by Reverse Transcription-Droplet Digital PCR
Authors: Au Ka-Ki , Chen Chunke , Chan Yee-Man , Wong Winsome Wing Sum , Lv Huibin , Mok Chris Ka Pun , Chow Chun-Kin
Published: October 2021

Viral transcription is an essential step of SARS-CoV-2 infection after invasion into the target cells. Antiviral drugs such as remdesivir, which is used to treat COVID-19 patients, targets the viral RNA synthesis. Understanding the mechanism of viral transcription may help to develop new therapeutic treatment by perturbing virus replication. In this study, we established 28 ddPCR assays and designed specific primers/probe sets to detect the RNA levels of 15 NSP, 9 ORF, and 4 structural genes of SARS-CoV-2. The transcriptional kinetics of these viral genes were determined longitudinally from the beginning of infection to 12 h postinfection in Caco-2 cells. We found that SARS-CoV-2 takes around 6 h to hijack the cells before the initiation of viral transcription process in human cells. Our results may contribute to a deeper understanding of the mechanisms of SARS-CoV-2 infection.
Molecular Characterization of Staphylococcus aureus Isolated from Human and Food Samples in Northern Algeria
Authors: Achek Rachid , El-Adawy Hosny , Hotzel Helmut , Hendam Ashraf , Tomaso Herbert , Ehricht Ralf , Neubauer Heinrich , Nabi Ibrahim , Hamdi Taha Mossadak , Monecke Stefan
Published: October 2021

Staphylococcus aureus is a commensal resident of the skin and nasal cavities of humans and can cause various infections. Some toxigenic strains can contaminate food matrices and cause foodborne intoxications. The present study aimed to provide relevant information (clonal complex lineages, agr types, virulence and antimicrobial resistance-associated genes) based on DNA microarray analyses as well as the origins and dissemination of several circulating clones of 60 Staphylococcus aureus isolated from food matrices (n = 24), clinical samples (n = 20), and nasal carriers (n = 16) in northern Algeria. Staphylococcus aureus were genotyped into 14 different clonal complexes. Out of 60 S. aureus, 13 and 10 isolates belonged to CC1-MSSA and CC97-MSSA, respectively. The CC 80-MRSA-IV was the predominant S. aureus strain in clinical isolates. The accessory gene regulator allele agr group III was mainly found among clinical isolates (70.4%). Panton–Valentine leukocidin genes lukF/lukS-PV were detected in 13.3% of isolates that all belonged to CC80-MRSA. The lukF/S-hlg, hlgA, and hla genes encoding for hemolysins and leucocidin components were detected in all Staphylococcusaureus isolates. Clinical and food isolates harbored more often the antibiotic resistance genes markers. Seventeen (28.3%) methicillin-resistant Staphylococcus aureus carrying the mecA gene localized on a SCCmec type IV element were identified. The penicillinase operon (blaZ/I/R) was found in 71.7% (43/60) of isolates. Food isolates belonging to CC97-MSSA carried several antibiotic resistance genes (blaZ, ermB, aphA3, sat, tetM, and tetK). The results of this study showed that all clones were found in their typical host, but interestingly, some nasal carriers had isolates assigned to CC705 thought to be absent in humans. The detection of MRSA strains among food isolates should be considered as a potential public health risk. Therefore, controlling the antibiotics prescription for a rational use in human and animal infections is mandatory.
Curry Leaf Triggers Cell Death of P. gingivalis with Membrane Blebbing
Authors: Nakao Ryoma , Ikeda Tsuyoshi , Furukawa Soichi , Morinaga Yasushi
Published: October 2021

Periodontal disease has become a serious public health problem, as indicated by accumulating evidence that periodontal disease is not only a major cause of tooth loss but is also associated with various systemic diseases. The present study assessed the anti-bacterial activities of three herbal products (curry leaf, clove, and cinnamon) against Porphyomonas gingivalis, a keystone pathogen for periodontal diseases. The curry leaf extract (CLE) showed the strongest growth inhibitory activity among them, and the activity was maintained even after extensive heat treatment. Of note, while clove and cinnamon extracts at sub-minimum inhibitory concentrations (sub-MICs) significantly enhanced the biofilm formation of P. gingivalis, CLE at sub-MIC did not have any effect on the biofilm formation. The MIC of CLE against P. gingivalis was higher than those against a wide range of other oral bacterial species. P. gingivalis cells were completely killed within 30 min after treatment with CLE. Spatiotemporal analysis using high-speed atomic force microscopy revealed that CLE immediately triggered aberrant membrane vesicle formation on the bacterial surface. Bacterial membrane potential assay revealed that CLE induced depolarization of the bacterial membrane. Taken together, these findings suggest the mechanism behind early bactericidal activity of CLE and its therapeutic applicability in patients with periodontal diseases.
Fungi Inhabiting the Wheat Endosphere
Authors: Błaszczyk Lidia , Salamon Sylwia , Mikołajczak Katarzyna
Published: October 2021

Wheat production is influenced by changing environmental conditions, including climatic conditions, which results in the changing composition of microorganisms interacting with this cereal. The group of these microorganisms includes not only endophytic fungi associated with the wheat endosphere, both pathogenic and symbiotic, but also those with yet unrecognized functions and consequences for wheat. This paper reviews the literature in the context of the general characteristics of endophytic fungi inhabiting the internal tissues of wheat. In addition, the importance of epigenetic regulation in wheat–fungus interactions is recognized and the current state of knowledge is demonstrated. The possibilities of using symbiotic endophytic fungi in modern agronomy and wheat cultivation are also proposed. The fact that the current understanding of fungal endophytes in wheat is based on a rather small set of experimental conditions, including wheat genotypes, plant organs, plant tissues, plant development stage, or environmental conditions, is recognized. In addition, most of the research to date has been based on culture-dependent methods that exclude biotrophic and slow-growing species and favor the detection of fast-growing fungi. Additionally, only a few reports of studies on the entire wheat microbiome using high-throughput sequencing techniques exist. Conducting comprehensive research on the mycobiome of the endosphere of wheat, mainly in the context of the possibility of using this knowledge to improve the methods of wheat management, mainly the productivity and health of this cereal, is needed.
Defining the Prion Type of Fatal Familial Insomnia
Authors: Jürgens-Wemheuer Wiebke , Wrede Arne , Schulz-Schaeffer Walter
Published: October 2021

Fatal familial insomnia (FFI) belongs to the genetic human transmissible spongiform encephalopathies (TSE), such as genetic Creutzfeldt-Jakob disease (CJD) or Gerstmann-Straeussler-Scheinker syndrome (GSS). Here, we analyzed the properties of the pathological prion protein in six FFI cases by Western blot analysis, a protein aggregate stability assay, and aggregate deposition characteristics visualized with the paraffin-embedded tissue blot. While in all cases the unglycosylated fragment in Western blot analysis shared the same size with sporadic CJD prion type 2, the reticular/synaptic deposition pattern of the prion aggregates resembled the ones found in sporadic CJD type 1 (CJD types according to the Parchi classification from 1999). Regarding the conformational stability against denaturation with GdnHCl, FFI prion aggregates resembled CJD type 1 more than type 2. Our results suggest that the size of the proteinase-K-resistant fragments is not a valid criterion on its own. Additional criteria supplying information about conformational differences or similarities need to be taken into account. FFI may resemble a prion type with its own conformation sharing properties partly with type 1 and type 2 prions.
Zinc Binding to NAP-Type Neuroprotective Peptides: Nuclear Magnetic Resonance Studies and Molecular Modeling
Authors: Lupaescu Ancuta-Veronica , Mocanu Cosmin Stefan , Drochioiu Gabi , Ciobanu Catalina-Ionica
Published: October 2021

Aggregation of amyloid-β peptides (Aβ) is a hallmark of Alzheimer’s disease (AD), which is affecting an increasing number of people. Hence, there is an urgent need to develop new pharmaceutical treatments which could be used to prevent the AD symptomatology. Activity-dependent neuroprotective protein (ADNP) was found to be deficient in AD, whereas NAP, an 8-amino-acid peptide (1NAPVSIPQ8) derived from ADNP, was shown to enhance cognitive function. The higher tendency of zinc ion to induce Aβ aggregation and formation of amorphous aggregates is also well-known in the scientific literature. Although zinc binding to Aβ peptides was extensively investigated, there is a shortage of knowledge regarding the relationship between NAP peptide and zinc ions. Therefore, here, we investigated the binding of zinc ions to the native NAP peptide and its analog obtained by replacing the serine residue in the NAP sequence with tyrosine (1NAPVYIPQ8) at various molar ratios and pH values by mass spectrometry (MS) and nuclear magnetic resonancespectroscopy (NMR). Matrix-assisted laser desorption/ionization time-of-flight (MALDI ToF) mass spectrometry confirmed the binding of zinc ions to NAP peptides, while the chemical shift of Asp1, observed in 1H-NMR spectra, provided direct evidence for the coordinating role of zinc in the N-terminal region. In addition, molecular modeling has also contributed largely to our understanding of Zn binding to NAP peptides.
Prophylactic Peripheral Blood Stem Cell Collection in Patients with Extensive Bone-Marrow Infiltration of Neuroendocrine Tumours Prior to Peptide Receptor Radionuclide Therapy with 177Lu-DOTATATE
Authors: Sabet Amir , Mader Nicolai , Bittenbring Jörg Thomas , Khreish Fadi , Grünwald Frank , Biersack Hans Jürgen , Ezziddin Samer
Published: October 2021

Peptide receptor radionuclide therapy (PRRT) of metastatic neuroendocrine tumors (NET) can be successfully repeated but may eventually be dose-limited. Since 177Lu-DOTATATE dose limitation may come from hematological rather than renal function, hematological peripheral blood stem cell backup might be desirable. Here, we report our initial experience of peripheral blood stem-cell collection (PBSC) in patients with treatment-related cytopenia and therefore high risk of bone-marrow failure. Five patients with diffuse bone-marrow infiltration of NET and relevant myelosuppression (≥grade 2) received PBSC before one PRRT cycle with 177Lu-DOTATATE (7.6 ± 0.8 GBq/cycle). Standard stem-cell mobilization with Granulocyte-colony stimulating factor (G-CSF) was applied, and successful PBSC was defined as a collection of >2 × 106/kg CD34+ cells. In case of initial failure, Plerixafor was administered in addition to G-CSF prior to apheresis. PBSC was successfully performed in all patients with no adverse events. Median cumulative activity was 44.8 GBq (range, 21.3–62.4). Three patients had been previously treated with PRRT, two of which needed the addition of Plerixafor for stem-cell mobilization. Only one of five patients required autologous peripheral blood stem-cell transplantation during the median follow up time of 28 months. PBSC collection seems to be feasible in NET with bone-marrow involvement and might be worth considering as a backup strategy prior to PRRT, in order to overcome dose-limiting bone-marrow toxicity.
New Frontiers in Cancer Imaging and Therapy Based on Radiolabeled Fibroblast Activation Protein Inhibitors: A Rational Review and Current Progress
Authors: Imlimthan Surachet , Moon Euy , Rathke Hendrik , Afshar-Oromieh Ali , Rösch Frank , Rominger Axel , Gourni Eleni
Published: October 2021

Over the past decade, the tumor microenvironment (TME) has become a new paradigm of cancer diagnosis and therapy due to its unique biological features, mainly the interconnection between cancer and stromal cells. Within the TME, cancer-associated fibroblasts (CAFs) demonstrate as one of the most critical stromal cells that regulate tumor cell growth, progression, immunosuppression, and metastasis. CAFs are identified by various biomarkers that are expressed on their surfaces, such as fibroblast activation protein (FAP), which could be utilized as a useful target for diagnostic imaging and treatment. One of the advantages of targeting FAP-expressing CAFs is the absence of FAP expression in quiescent fibroblasts, leading to a controlled targetability of diagnostic and therapeutic compounds to the malignant tumor stromal area using radiolabeled FAP-based ligands. FAP-based radiopharmaceuticals have been investigated strenuously for the visualization of malignancies and delivery of theranostic radiopharmaceuticals to the TME. This review provides an overview of the state of the art in TME compositions, particularly CAFs and FAP, and their roles in cancer biology. Moreover, relevant reports on radiolabeled FAP inhibitors until the year 2021 are highlighted—as well as the current limitations, challenges, and requirements for those radiolabeled FAP inhibitors in clinical translation.
Identification of a Novel Neuropeptide S Receptor Antagonist Scaffold Based on the SHA-68 Core
Authors: Zarkin Allison , Jahan Rajwana , Uprety Rajendra , Zhang Yanan , McElhinny Charles , Snyder Rodney , Gay Elaine , Jewula Gabriel , Bool Heather , Clark Stewart D , Runyon Scott
Published: October 2021

Activation of the neuropeptide S receptor (NPSR) system has been shown to produce anxiolytic-like actions, arousal, and enhance memory consolidation, whereas blockade of the NPSR has been shown to reduce relapse to substances of abuse and duration of anesthetics. We report here the discovery of a novel core scaffold (+) N-benzyl-3-(2-methylpropyl)-1-oxo-3-phenyl-1H,3H,4H,5H,6H,7H-furo[3,4-c]pyridine-5-carboxamide with potent NPSR antagonist activity in vitro. Pharmacokinetic parameters demonstrate that 14b reaches pharmacologically relevant levels in plasma and the brain following intraperitoneal (i.p.) administration, but is cleared rapidly from plasma. Compound 14b was able to block NPS (0.3 nmol)-stimulated locomotor activity in C57/Bl6 mice at 3 mg/kg (i.p.), indicating potent in vivo activity for the structural class. This suggests that 14b can serve as a useful tool for continued mapping of the pharmacological functions of the NPS receptor system.
Ustekinumab Dosing Individualization in Crohn’s Disease Guided by a Population Pharmacokinetic–Pharmacodynamic Model
Authors: Aguiar Zdovc Jurij , Hanžel Jurij , Kurent Tina , Sever Nejc , Koželj Matic , Smrekar Nataša , Novak Gregor , Štabuc Borut , Dreesen Erwin , Thomas Debby , Vovk Tomaž , Ostanek Barbara , Drobne David , Grabnar Iztok
Published: October 2021

Ustekinumab is a monoclonal antibody used in Crohn’s disease (CD). Dose optimization in case of non-response and the role of pharmacokinetic–pharmacodynamic (PK-PD) monitoring remain unresolved dilemmas in clinical practice. We aimed to develop a population PK-PD model for ustekinumab in CD and simulate efficacy of alternative dosing regimens. We included 57 patients and recorded their characteristics during 32 weeks after starting with ustekinumab therapy. Serum ustekinumab concentration was prospectively measured and fecal calprotectin (FC) concentration was used to monitor the disease activity. Ustekinumab PK-PD was described by a two-compartment target-mediated drug disposition model linked to an indirect response model. Lower fat-free mass, higher serum albumin, previous non-exposure to biologics, FCGR3A-158 V/V variant and lower C-reactive protein were associated with higher ustekinumab exposure. Model-based simulation suggested that 41.9% of patients receiving standard dosing achieve biochemical remission at week 32. In patients not achieving remission with standard dosing at week 16, transition to 4-weekly subcutaneous maintenance dosing with or without intravenous reinduction resulted in comparably higher remission rates at week 32 (51.1% vs. 49.2%, respectively). Our findings could be used to guide stratified ustekinumab treatment in CD, particularly in patients with unfavorable characteristics, who might benefit from early transition to 4-weekly maintenance dosing.
Protease-Triggered Release of Stabilized CXCL12 from Coated Scaffolds in an Ex Vivo Wound Model
Authors: Spiller Sabrina , Wippold Tom , Bellmann-Sickert Kathrin , Franz Sandra , Saalbach Anja , Anderegg Ulf , Beck-Sickinger Annette G.
Published: October 2021

Biomaterials are designed to improve impaired healing of injured tissue. To accomplish better cell integration, we suggest to coat biomaterial surfaces with bio-functional proteins. Here, a mussel-derived surface-binding peptide is used and coupled to CXCL12 (stromal cell-derived factor 1α), a chemokine that activates CXCR4 and consequently recruits tissue-specific stem and progenitor cells. CXCL12 variants with either non-releasable or protease-mediated-release properties were designed and compared. Whereas CXCL12 was stabilized at the N-terminus for protease resistance, a C-terminal linker was designed that allowed for specific cleavage-mediated release by matrix metalloproteinase 9 and 2, since both enzymes are frequently found in wound fluid. These surface adhesive CXCL12 derivatives were produced by expressed protein ligation. Functionality of the modified chemokines was assessed by inositol phosphate accumulation and cell migration assays. Increased migration of keratinocytes and primary mesenchymal stem cells was demonstrated. Immobilization and release were studied for bioresorbable PCL-co-LC scaffolds, and accelerated wound closure was demonstrated in an ex vivo wound healing assay on porcine skin grafts. After 24 h, a significantly improved CXCL12-specific growth stimulation of the epithelial tips was already observed. The presented data display a successful application of protein-coated biomaterials for skin regeneration.