bluuebunny/crossref_metadata_2025 huggingface dataset:
Dark Current Reduction and Performance Improvements in Graphene/Silicon Heterojunction Photodetectors Obtained Using a Non-Stoichiometric HfOx Thin Oxide Layer
Authors: Qu Tao , Fan Jibin , Wei Xing
Published: February 2024

Graphene/silicon heterojunction photodetectors suffer from a high dark current due to the high surface states and low barrier height at the interface, which limits their application. In this study, we introduce an HfOx interfacial layer via magnetron sputtering to address this issue. With this new structure, the dark current is reduced by six times under a bias voltage of −2 V. Under 460 nm illumination, the responsivity is 0.228A/W, the detectivity is 1.15 × 1011 cmHz1/2W−1, and the noise equivalent power is 8.75 × 10−5 pW/Hz1/2, demonstrating an excellent weak light detection capability. Additionally, the oxygen vacancies in the HfOx interfacial layer provide a conductive channel for charge carriers, resulting in a 2.03-fold increase in photocurrent and an external quantum efficiency of 76.5%. The photodetector maintains good photoresponse ability at a low bias voltage. This work showcases the outstanding performance of HfOx films as interfacial layer materials and provides a new solution for high-performance photodetectors, as well as a new path to improve the photovoltaic conversion efficiency of solar cells.
Enhancing Sustainability in Potato Crop Production: Mitigating Greenhouse Gas Emissions and Nitrate Accumulation in Potato Tubers through Optimized Nitrogen Fertilization
Authors: Seno Nascimento Camila , Seno Nascimento Carolina , de Jesus Pereira Breno , Soares Silva Paulo Henrique , Pessôa da Cruz Mara Cristina , Bernardes Cecílio Filho Arthur
Published: February 2024

The complex ramifications of global climate change, which is caused by heightened concentrations of greenhouse gases in the Earth’s atmosphere, are deeply concerning. Addressing this crisis necessitates the immediate implementation of adaptive mitigation strategies, especially within the agricultural sector. In this context, this study aimed to assess how the supply of nitrogen (N) (0, 70, 140, and 210 kg N ha−1) in the forms of ammonium nitrate and urea affects the agronomic performance, food quality, greenhouse gas emissions (GHG), and carbon footprint of potato plants. The examined hypothesis was that by precisely calibrating N doses alongside appropriate sourcing, over-fertilization in potato cultivation can be mitigated. A decline in stomatal conductance and net photosynthetic rate disturbs physiological mechanisms, reflecting in biomass production. Application of 136 kg N ha−1 as urea showed a remarkable yield increase compared to other doses and sources. The highest nitrate content in potato tubers was achieved at 210 kg N ha−1 for both sources, not exceeding the limit (200 mg kg−1 of fresh mass) recommended for human consumption. The lowest carbon footprint was obtained when 70 kg N ha−1 was applied, around 41% and 26% lower than when 210 kg N ha−1 and 140 kg N ha−1 were applied, respectively. The results demonstrated that over-fertilization not only worsened the yield and tuber quality of potato plants, but also increased greenhouse gas emissions. This information is valuable for establishing an effective fertilization program for the potato crop and reducing carbon footprint.
Effect of Dietary Supplementation with Omega-3 Fatty Acid on the Generation of Regulatory T Lymphocytes and on Antioxidant Parameters and Markers of Oxidative Stress in the Liver Tissue of IL−10 Knockout Mice
Authors: Campanari Daniela Dalpubel , Cipriano Ualter Guilherme , Fraga-Silva Thais Fernanda de Campos , Ramalho Leandra Náira Zambelli , Ovidio Paula Payão , Jordão Júnior Alceu Afonso , Bonato Vânia Luiza Deperon , Ferriolli Eduardo
Published: February 2024

Introduction: chronic low-grade inflammation, or inflammaging, emerges as a crucial element in the aging process and is associated with cardiovascular and neurological diseases, sarcopenia, and malnutrition. Evidence suggests that omega-3 fatty acids present a potential therapeutic agent in the prevention and treatment of inflammatory diseases, mitigating oxidative stress, and improving muscle mass, attributes that are particularly relevant in the context of aging. The objective of the present study was to evaluate the effectiveness of supplementation with omega-3 fish oil in improving the immune response and oxidative stress in knockout mice for interleukin IL−10 (IL−10−/−). Material and methods: female C57BL/6 wild-type (WT) and interleukin IL−10 knockout (IL−10−/−) mice were fed during 90 days with a standard diet (control groups), or they were fed/supplemented with 10% of the omega-3 polyunsaturated fatty acid diet (omega-3 groups). Muscle, liver, intestinal, and mesenteric lymph node tissue were collected for analysis. Results: the IL−10−/−+O3 group showed greater weight gain compared to the WT+O3 (p = 0.001) group. The IL−10−/−+O3 group exhibited a higher frequency of regulatory T cells than the IL−10−/− group (p = 0.001). It was found that animals in the IL−10−/−+O3 group had lower levels of steatosis when compared to the IL−10−/− group (p = 0.017). There was even greater vitamin E activity in the WT group compared to the IL−10−/−+O3 group (p = 0.001) and WT+O3 compared to IL−10−/−+O3 (p = 0.002), and when analyzing the marker of oxidative stress, MDA, an increase in lipid peroxidation was found in the IL−10−/−+O3 group when compared to the IL−10−/− group (p = 0.03). Muscle tissue histology showed decreased muscle fibers in the IL−10−/−+O3, IL−10−/−, and WT+O3 groups. Conclusion: the findings show a decrease in inflammation, an increase in oxidative stress markers, and a decrease in antioxidant markers in the IL−10−/−+O3 group, suggesting that supplementation with omega-3 fish oil might be a potential intervention for inflammaging that characterizes the aging process and age-related diseases.
Application of Nanoparticles in Human Nutrition: A Review
Authors: Altemimi Ammar B. , Farag Halgord Ali M. , Salih Tablo H. , Awlqadr Farhang H. , Al-Manhel Alaa Jabbar Abd , Vieira Italo Rennan Sousa , Conte-Junior Carlos Adam
Published: February 2024

Nanotechnology in human nutrition represents an innovative advance in increasing the bioavailability and efficiency of bioactive compounds. This work delves into the multifaceted dietary contributions of nanoparticles (NPs) and their utilization for improving nutrient absorption and ensuring food safety. NPs exhibit exceptional solubility, a significant surface-to-volume ratio, and diameters ranging from 1 to 100 nm, rendering them invaluable for applications such as tissue engineering and drug delivery, as well as elevating food quality. The encapsulation of vitamins, minerals, and antioxidants within NPs introduces an innovative approach to counteract nutritional instabilities and low solubility, promoting human health. Nanoencapsulation methods have included the production of nanocomposites, nanofibers, and nanoemulsions to benefit the delivery of bioactive food compounds. Nutrition-based nanotechnology and nanoceuticals are examined for their economic viability and potential to increase nutrient absorption. Although the advancement of nanotechnology in food demonstrates promising results, some limitations and concerns related to safety and regulation need to be widely discussed in future research. Thus, the potential of nanotechnology could open new paths for applications and significant advances in food, benefiting human nutrition.
Association between Intake of Edible Mushrooms and Algae and the Risk of Cognitive Impairment in Chinese Older Adults
Authors: Yang Yun , Zhu Danni , Qi Ran , Chen Yanchun , Sheng Baihe , Zhang Xinyu
Published: February 2024

Previous studies have investigated the association between diet and cognitive impairment, yet there is limited investigation into the link between edible mushrooms and algae intake and cognitive decline. This study aims to explore the association between edible mushrooms and algae intake and the risk of cognitive impairment in individuals aged 65 years and above in China. Cross-sectional data from the 2018 Chinese Longitudinal Healthy Longevity Survey (CLHLS) formed the basis of this study. Edible mushrooms and algae intake was evaluated using a simplified food frequency questionnaire (FFQ) and cognitive function was assessed using the Mini-Mental State Examination (MMSE). A binary logistic regression model was used to evaluate odds ratios (ORs) and 95% confidence intervals (CIs), with subgroup analysis conducted. Among 14,150 older adults, the average age was (85.33 ± 11.55), with a cognitive impairment prevalence of 22.7; multi-model adjustments showed a 25.3% lower probability of cognitive impairment for those occasionally consuming edible mushrooms and algae (OR: 0.747, 95% CI: 0.675~0.826). Furthermore, a 29% lower risk was observed in those with daily intake (OR: 0.710, 95% CI: 0.511~0.987). Subgroup analysis demonstrated significant risk reduction in women (OR: 0.589, 95% CI: 0.375~0.925, p = 0.022), individuals with disability in activities of daily living (OR: 0.568, 95% CI: 0.367~0.878, p = 0.011), and those with low social activity levels (OR: 0.671, 95% CI: 0.473~0.950, p = 0.025). This study concludes that edible mushrooms and algae intake significantly impacts the risk of cognitive impairment in older adults. These results provide insights and impetus for further research into this area. Additional cohort studies or intervention trials are necessary to confirm the potential benefits of edible mushrooms and algae in promoting cognitive health.
Consistency and Variability of the Human Milk Oligosaccharide Profile in Repeat Pregnancies
Authors: Renwick Simone , Rahimi Kamand , Sejane Kristija , Bertrand Kerri , Chambers Christina , Bode Lars
Published: February 2024

Human milk oligosaccharides (HMOs) are a set of complex carbohydrates and the third largest solid component of human milk, after lactose and lipids. To date, over 150 HMOs have been identified and the diversity of structures produced by lactating women is influenced by maternal genetics as well as other maternal, infant, and environmental factors. While the concentrations of individual HMOs have been shown to vary between individuals and throughout the course of lactation, the variability of HMO concentration profiles following different pregnancies occurring in the same woman is presently unknown. As such, the objective of this study was to compare HMO concentrations in human milk samples provided by the same women (n = 34) following repeat pregnancies. We leveraged existing human milk samples and metadata from the UC San Diego Human Milk Research Biorepository (HMB) and measured the concentrations of the 19 most abundant HMOs using high-performance liquid chromatography with fluorescence detection (HPLC-FL). By assessing dissimilarities in HMO concentration profiles, as well as concentration trends in individual structures between pregnancies of each participant, we discovered that HMO profiles largely follow a highly personalized and predictable trajectory following different pregnancies irrespective of non-genetic influences. In conclusion, this is the first study to assess the interactions between parity and time following delivery on variations in HMO compositions.
Exploring the Anti-Diabetic Potential of Quercetagitrin through Dual Inhibition of PTPN6 and PTPN9
Authors: Gone Geetanjali B. , Go Geonhui , Nam Gibeom , Jeong Woojoo , Kim Hyemin , Lee Soah , Chung Sang J.
Published: February 2024

Protein tyrosine phosphatases (PTPs) are pivotal contributors to the development of type 2 diabetes (T2DM). Hence, directing interventions towards PTPs emerges as a valuable therapeutic approach for managing type 2 diabetes. In particular, PTPN6 and PTPN9 are targets for anti-diabetic effects. Through high-throughput drug screening, quercetagitrin (QG) was recognized as a dual-target inhibitor of PTPN6 and PTPN9. We observed that QG suppressed the catalytic activity of PTPN6 (IC50 = 1 μM) and PTPN9 (IC50 = 1.7 μM) in vitro and enhanced glucose uptake by mature C2C12 myoblasts. Additionally, QG increased the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and insulin-dependent phosphorylation of Akt in mature C2C12 myoblasts. It further promoted the phosphorylation of Akt in the presence of palmitic acid, suggesting the attenuation of insulin resistance. In summary, our results indicate QG’s role as a potent inhibitor targeting both PTPN6 and PTPN9, showcasing its potential as a promising treatment avenue for T2DM.
Macro-B12 and Unexpectedly High Levels of Plasma B12: A Critical Review
Authors: Fedosov Sergey N. , Nexo Ebba
Published: February 2024

A low total plasma vitamin B12 supports a clinical suspicion of B12 deficiency, while the interpretation of an unexpectedly normal/high level is marred by controversies. Here, we critically review current knowledge on B12 in blood plasma, including the presence of the so-called “macro-B12”. The latter form is most often defined as the fraction of B12 that can be removed by precipitation with polyethylene glycol (PEG), a nonspecific procedure that also removes protein polymers and antibody-bound analytes. Plasma B12 includes B12 attached to transcobalamin and haptocorrin, and an increased concentration of one or both proteins almost always causes an elevation of B12. The total plasma B12 is measured by automated competitive binding assays, often incorrectly referred to as immunoassays, since the binding protein is intrinsic factor and not an antibody. An unexpectedly high level of B12 may be further explored using immunological measurements of haptocorrin and transcobalamin (optionally combined with e.g., size-exclusion chromatography). Nonspecific methods, such as PEG precipitation, are likely to give misleading results and cannot be recommended. Currently, the need for evaluation of a high B12 of unknown etiology is limited since other tests (such as measurements of methylmalonic acid) may better guide the diagnosis of B12 deficiency.
Royal Jelly and Fermented Soy Extracts—A Holistic Approach to Menopausal Symptoms That Increase the Quality of Life in Pre- and Post-menopausal Women: An Observational Study
Authors: Balan Andreea , Moga Marius Alexandru , Neculau Andrea Elena , Mitrica Maria , Rogozea Liliana , Ifteni Petru , Dima Lorena
Published: February 2024

Background: The objective of this study was to determine the effects of royal jelly and fermented soy extracts on menopausal symptoms and on quality of life in pre- and post-menopausal women. Materials and method: This prospective observational study was carried out in a Clinical Hospital of Brasov, Romania, during June 2020 and December 2021. Eighty pre- and post-menopausal women, aged between 45 and 60 years, were included in two groups. The first group (40 women) received a dietary supplement with fermented soy extract twice a day for eight weeks and the second group (40 women) received the same dietary supplement with fermented soy extracts and 1500 mg of royal jelly capsules for eight weeks. After the treatment, the MENQOL score, DASS-21 score, and the mean number and intensity of daily hot flushes were recorded and compared with baseline values. Results: After eight weeks of treatment, the score of the MENQOL questionnaire and all its domains’ scores decreased in comparison with the baseline in both groups (p < 0.001). Also, the DASS-21 score (p < 0.001), depression score (p < 0.001), anxiety score (p < 0.001), and stress score (p < 0.001) improved. The mean number and the intensity of hot flushes decreased in both groups (p < 0.001). Comparing these variables after the treatment in both groups, we observed that the women who received dietary supplements with fermented soy extracts and royal jelly capsules recorded better scores for MENQOL (vasomotor, physical, and psychosocial domains) and a more reduced mean number of daily hot flushes. Conclusions: This observational study suggests that both dietary fermented soy supplements and royal jelly capsules possess beneficial effects against menopausal symptoms, increase the quality of life in pre- and post-menopausal women, and that the effects might be significantly improved if those dietary supplements are administered in association.
Geriatric Nutritional Risk Index and First-Year Mortality in Incident Hemodialysis Patients
Authors: Song Gi Hyun , Choi Han Byul , Park Hayne Cho , Kim Do Hyoung , Lee Young-Ki , Cho AJin
Published: February 2024

Objective. The Geriatric Nutritional Risk Index is a simple nutritional screening method, and this study aimed to investigate the association between the initial Geriatric Nutritional Risk Index and all-cause mortality in incident patients in the first year after the initiation of hemodialysis. Materials and Methods. This study is a retrospective cohort study and used the Korean Renal Data System database. Patients who were eligible for Geriatric Nutritional Risk Index assessment and underwent hemodialysis from January 2016 to December 2019 were included. The primary outcome was all-cause mortality, and outcome evaluation was performed in December 2020. A Cox proportional hazard model was used to analyze the association between the Geriatric Nutritional Risk Index and mortality. Results. A total of 10,545 patients were included, and the mean age was 63.9 ± 3.7 years. The patients were divided into four groups by the quartile of the Geriatric Nutritional Risk Index with a mean value of 96.2 ± 8.2. During the study period, 545 (5.2%) deaths occurred. The surviving patients had higher Geriatric Nutritional Risk Index values than ones who died in the first year of hemodialysis initiation (96.6 ± 7.5 vs. 88.2 ± 9.3, p < 0.001). Quartile 1 (Geriatric Nutritional Risk Index < 91.8) showed a significantly increased risk of all-cause (Hazard Ratio: 2.56; 95% Confidence Interval: 2.13–3.09; p < 0.001) and cardiovascular mortality (Hazard Ratio: 22.29; 95% Confidence Interval: 1.71– 3.08; p < 0.001) at the first year in comparison with Quartile 4 (Geriatric Nutritional Risk Index ≥ 101.3). In areas under the receiver-operating characteristic curves of all-cause mortality, the Geriatric Nutritional Risk Index model improved predictive values, compared to the baseline model. The area with the Geriatric Nutritional Risk Index model was significantly higher than the one with a model including albumin or body mass index (p < 0.001). Conclusions. These findings suggest that a low Geriatric Nutritional Risk Index (<91.8) is associated with first-year all-cause and cardiovascular mortality in patients who start hemodialysis and may be a useful and reproducible tool for assessing prognoses in this population.
Menopause Hot Flashes and Molecular Mechanisms Modulated by Food-Derived Nutrients
Authors: Forma Ewa , Urbańska Karina , Bryś Magdalena
Published: February 2024

The causes of vasomotor symptoms, including hot flashes, are not fully understood, may be related to molecular factors, and have a polygenic architecture. Nutrients and bioactive molecules supplied to the body with food are metabolized using various enzymatic pathways. They can induce molecular cell signaling pathways and, consequently, activate effector proteins that modulate processes related to hot flashes in menopausal women. In this review, we analyzed the literature data from the last 5 years, especially regarding genome-wide association study (GWAS) analysis, and selected molecular factors and cell signaling pathways that may potentially be related to hot flashes in women. These are the kisspeptin-GnRH pathway, adipocyte-derived hormones, aryl hydrocarbon receptor signaling, catechol estrogens and estrogen sulfotransferase, inflammatory and oxidative stress biomarkers, and glucose availability. Then, single compounds or groups of food ingredients were selected that, according to experimental data, influence the course of the discussed molecular pathways and thus can be considered as potential natural therapeutic agents to effectively reduce the troublesome symptoms of menopause in women.
Cost and Affordability of Habitual and Recommended Diets in Welfare-Dependent Households in Australia
Authors: Lewis Meron , Nash Stephen , Lee Amanda J.
Published: February 2024

It is crucial to ensure healthy diets are affordable in low socioeconomic groups, such as welfare-dependent households, who experience higher rates of diet-related disease than others. This study assessed the cost of habitual (unhealthy) and recommended (healthy) diets in six welfare-dependent and six other, comparable Australian households, using either popular branded products or the cheapest available alternatives. It also assessed diet affordability in welfare-dependent households, before and after modest increases in government welfare payments introduced in early September 2023. Results confirmed that recommended diets were less expensive than habitual diets in all households unless the cheapest available products were included. This strategy reduced habitual diet costs by 35–37% and recommended diet costs by 30–32%. The lower cost differential could aid perceptions that healthy foods are more expensive than unhealthy foods. In April 2023, 23–37% of the income of welfare-dependent households with children was required to purchase recommended diets; this reduced only to 20–35% in September 2023. Hence, the increases in welfare payments were insufficient to meaningfully improve the affordability of healthy diets in the most vulnerable Australians. In the current cost-of-living crisis, there is an urgent need for more welfare support to help purchase healthy diets. Monitoring of diet cost and affordability is also required.
Exploring the Dynamic Relationship between the Gut Microbiome and Body Composition across the Human Lifespan: A Systematic Review
Authors: Komodromou Ifigeneia , Andreou Eleni , Vlahoyiannis Angelos , Christofidou Maria , Felekkis Kyriacos , Pieri Myrtani , Giannaki Christoforos D.
Published: February 2024

This systematic review aimed to identify different gut microbiome profiles across the human lifespan and to correlate such profiles with the body composition. PubMed, Scopus, and Cochrane were searched from inception to March 2022. Sixty studies were included in this systematic review. Overall, the gut microbiome composition in overweight participants exhibited decreased α-diversity, decreased levels of the phylum Bacteroidetes and its taxa, and increased levels of the phylum Firmicutes, its taxa, and the Firmicutes/Bacteroidetes ratio, in comparison to normal-weight participants. Other body composition parameters showed similar correlations. Fat mass and waist circumference were found to correlate positively with the Firmicutes taxa and negatively with the Bacteroidetes taxa. In contrast, lean body mass and muscle mass demonstrated a positive correlation with the Bacteroidetes taxa. Notably, these correlations were more pronounced in athletes than in obese and normal-weight individuals. The composition of the gut microbiome is evidently different in overweight individuals or athletes of all age groups, with the former tending towards decreased Bacteroidetes taxa and increased Firmicutes taxa, while a reversed relationship is observed concerning athletes. Further studies are needed to explore the dynamic relationship between energy intake, body composition, and the gut microbiome across the human lifespan.
Access to the Health Care System of Undocumented Moroccan Migrant Slum Dwellers in Southern Spain: A Qualitative Study
Authors: Plaza del Pino Fernando Jesus , Chraibi Ghita , Molina-Gallego Brigida , Humanes-García Maria , Sánchez-Ojeda Maria Angustias , Ugarte-Gurrutxaga María Idoia
Published: February 2024

Spain has grown economically due to the recent boosts in the industrial sector, the agricultural sector, construction and services. Those who carry out agricultural tasks are mainly undocumented immigrants living in marginal neighborhoods. Objectives: to know the perception of undocumented Moroccan migrants living in marginal neighborhoods regarding access to the Public Health System. Methods: A qualitative method with a phenomenological approach was used to get closer to the experience of the participants in the study. In this work, 24 semi-structured interviews were conducted following a guide with a set of open questions to facilitate an in-depth discussion of the topics of interest. The participants were given an informed consent form, which guaranteed anonymity and confidentiality regarding the information obtained. For this, codes were used to identify them. The data were stored, managed, classified, and organized with the ATLAS-ti 9 software. Results: access and use of health services by the immigrants in the study was difficult due to communication problems related to language and culture, the discriminatory attitude and lack of cultural competence of health personnel, and the location of the neighborhoods (which were marginal far from urban centers), as well as the lack of transportation to health centers. Conclusions: it is an ethical imperative of the Health System to offer greater attention to the population in situations of extreme vulnerability, implement intercultural mediators and train health professionals in cultural competence.
Pathogens Causing Pediatric Community Acquired Urinary Tract Infections and Their Increasing Antimicrobial Resistance: A Nationwide Study
Authors: Shkalim Zemer Vered , Ashkenazi Shai , Levinsky Yoel , Richenberg Yael , Jacobson Eyal , Nathanson Shay , Shochat Tzippy , Kushnir Shiri , Cohen Moriya , Cohen Avner Herman
Published: February 2024

Urinary tract infections (UTIs) in childhood are common and are associated with considerable acute morbidity and long-term complications. The need for updated data to optimize empiric antibiotic therapy is crucial. We aimed to investigate the pathogens causing pediatric community acquired UTIs, their correlation with demographic characteristics, and trends in their antimicrobial resistance. This nationwide cross-sectional study included all 53,203 children (<18 years) diagnosed with UTI in community outpatient clinics in the following selected years: 2007, 2011, 2015, 2019 and 2021. Escherichia coli (E. coli) (82.1%) was the most common uropathogen, followed by Enterobacter, Klebsiella, Proteus, Pseudomonas, and Enterococcus species. The bacterial distribution displayed statistically significant (p < 0.0001) gender- and sector-specific patterns with a higher relative prevalence of non-E. coli UTI in Jewish and males. The rate of extended-spectrum beta-lactamase-positive E. coli increased substantially and significantly (p < 0.001) from only 6.1% in 2007 to 25.4% in 2021. Most non-E. coli uropathogens exhibited resistance to commonly used empiric antibiotics for UTIs in children. These findings are significant in guiding optimal empiric antibiotic treatment for pediatric community acquired UTIs. The resistance of uropathogens to antimicrobials is region- and time-dependent. Therefore, the periodic and local assessment of antibiotic resistance trends is essential to update guidelines and provide the most appropriate antibacterial therapy for children with UTIs.
Survival of Escherichia coli in Edible Land Snails: Implications for Heliciculture and Public Health
Authors: Tanyitiku Mary Nkongho , Nicholas Graeme , Sullivan Jon J. , Petcheu Igor C. Njombissie , On Stephen L. W.
Published: February 2024

Background: Land snails are considered a delicacy in many countries in Europe and sub-Saharan Africa. However, the interaction of microbial pathogens with land snails may present a public health threat when handling and/or consuming snails. This study examines the survival of Escherichia coli in edible land snails in a model system. Methods: Well-studied Shigatoxigenic (STEC) and non-STEC strains were compared. Mature Helix spp. were experimentally fed with E. coli-inoculated oats for 48 h. The snail feces after inoculation were periodically sampled and cultured for a 30-day period and subjected to microbiological analyses. Results: The average rate of decline of the non-STEC strain CSH-62 in the feces of live snails was significantly (p < 0.05) faster than that of STEC ERL 06-2503. In addition, the viable population of E. coli ERL 06-2503 significantly (p < 0.05) persisted for a longer time in the intestine of land snails than E. coli CSH-62. Conclusion: The results showed that the viable population of the E. coli strains examined demonstrated first-order kinetics, and their survival (CFU/mL) appeared significantly (p < 0.05) dependent on the E. coli pathotype. In addition, the continuous enumeration of E. coli in snail faeces indicated that land snails could serve as a mode of transmission of microbial pathogens to susceptible hosts, including humans. Further research is recommended to better quantify the direct and indirect health risks of pathogen transmission by edible snails to humans.
Autochthonous and Imported Visceral Leishmaniasis in Bulgaria—Clinical Experience and Treatment of Patients
Authors: Vutova Kamenna , Yancheva-Petrova Nina , Tchipeva Rossitsa , Velev Valeri
Published: February 2024

Visceral leishmaniasis (VL) is a severe endemic disease with a fatal outcome if left untreated. The symptoms of patients are diverse and atypical. Against the background of anemia and pancytopenia, the condition of the patients gradually worsens with marked cachexia. Through sharing our experience, we aim to draw attention to this deadly disease. Clinical and laboratory data for 58 patients with VL treated over a forty-five-year period are presented. The diagnosis was established within a duration of 1 to 28 months of illness. Continuous fever (38–42 °C), splenomegaly, hepatomegaly, severe anemia (decreased hemoglobin to lowest values of 31 g/L), leucopenia (lowest values of leucocytes et 0.5 g/L), and thrombocytopenia (reduced thrombocyte count to 29 g/L) were observed. The diagnosis was made on the basis of microscopic evidence of amastigote forms in bone marrow smears and serological tests. The patients were treated with Glucantime for 17 to 21 days. Relapses were observed in seven patients (12.1%) and fatal outcome was observed in two patients (3.5%) during treatment, who developed acute respiratory and cardiovascular failure. In Bulgaria, Visceral leishmaniasis is primarily endemic in the southern regions and should be suspected not only in patients who have returned from tropical and subtropical countries, but also in those who have not traveled abroad. The challenges associated with VL stem from delayed diagnosis of patients, as this disease remains unrecognized by physicians.
TRPV4 Activation during Guinea Pig Airway Smooth Muscle Contraction Promotes Ca2+ and Na+ Influx
Authors: Montaño Luis M. , Carbajal-García Abril , Casas-Hernández María F. , Arredondo-Zamarripa David , Reyes-García Jorge
Published: February 2024

Airway smooth muscle (ASM) contraction is determined by the increase in intracellular Ca2+ concentration ([Ca2+]i) caused by its release from the sarcoplasmic reticulum (SR) or by extracellular Ca2+ influx. Major channels involved in Ca2+ influx in ASM cells are L-type voltage-dependent Ca2+ channels (L-VDCCs) and nonselective cation channels (NSCCs). Transient receptor potential vanilloid 4 (TRPV4) is an NSCC recently studied in ASM. Mechanical stimuli, such as contraction, can activate TRPV4. We investigated the possible activation of TRPV4 by histamine (His)- or carbachol (CCh)-induced contraction in guinea pig ASM. In single myocytes, the TRPV4 agonist (GSK101) evoked an increase in [Ca2+]i, characterized by a slow onset and a plateau phase. The TRPV4 antagonist (GSK219) decreased channel activity by 94%, whereas the Ca2+-free medium abolished the Ca2+ response induced by GSK101. Moreover, GSK101 caused Na+ influx in tracheal myocytes. GSK219 reduced the Ca2+ peak and the Ca2+ plateau triggered by His or CCh. TRPV4 blockade shifted the concentration–response curve relating to His and CCh to the right in tracheal rings and reduced the maximal contraction. Finally, the activation of TRPV4 in single myocytes increased the Ca2+ refilling of the SR. We conclude that contraction of ASM cells after stimulation with His or CCh promotes TRPV4 activation, the subsequent influx of Ca2+ and Na+, and the opening of L-VDCCs. The entry of Ca2+ into ASM cells via TRPV4 and L-VDCCs contributes to optimal smooth muscle contraction.
Molecular Imaging of Fibrosis in Benign Diseases: An Overview of the State of the Art
Authors: Zhang Yongbai , Huang Wenpeng , Jiao Hao , Song Lele , Kang Lei
Published: February 2024

Fibrosis is a progressive pathological process participating in the progression of many diseases and can ultimately result in organ malfunction and failure. Around 45% of deaths in the United States are believed to be attributable to fibrotic disorders, and there are no favorable treatment regiments available to meet the need of blocking fibrogenesis, reversing established fibrosis, and curing diseases, especially in the terminal stage. Therefore, early detection and continuous monitoring provide valuable benefits for patients. Among all the advanced techniques developed in recent years for fibrosis evaluation, molecular imaging stands out with its distinct advantage of visualizing biochemical processes and patterns of target localization at the molecular and cellular level. In this review, we summarize the current state of the art in molecular imaging of benign fibrosis diseases. We will first introduce molecular pathways underlying fibrosis processes and potential targets. We will then elaborate on molecular probes that have been developed thus far, expounding on their mechanisms and current states of translational advancement. Finally, we will delineate the extant challenges impeding further progress in this area and the prospective benefits after overcoming these problems.
Graft-Versus-Host Disease: Can Biomarkers Assist in Differential Diagnosis, Prognosis, and Therapeutic Strategy?
Authors: Alexoudi Vaia-Aikaterini , Gavriilaki Eleni , Cheva Angeliki , Sakellari Ioanna , Papadopoulou Stavroula , Paraskevopoulos Konstantinos , Vahtsevanos Konstantinos
Published: February 2024

A crucial complication after allogeneic hematopoietic cell transplantation (alloHCT), namely, acute graft-versus-host disease (aGVHD), occurs in about 50% of transplant recipients, leading to high morbidity and mortality. Thus far, the diagnosis of GVHD has been mainly established through clinical features and histologic or laboratory evidence of periductal lymphocyte infiltration, fibroplasia, and mixed lymphocytic and plasmocytic inflammation. Intensive research is focused on identifying biomarkers for the early diagnosis, prediction of disease, response to treatment, prognosis, and risk stratification of patients. The serum biomolecules that have been investigated are reported and summarized. Moreover, oral tissue involvement in GVHD is described, and other biomarkers that have been proposed, such as saliva, are analyzed. Future research is highlighted as a necessity in order for these biomarkers to be validated and quantified for use in clinical practice.
Magnetic Hyperthermia Therapy for High-Grade Glioma: A State-of-the-Art Review
Authors: Rodriguez Benjamin , Rivera Daniel , Zhang Jack Y. , Brown Cole , Young Tirone , Williams Tyree , Huq Sakibul , Mattioli Milena , Bouras Alexandros , Hadjpanayis Constantinos G.
Published: February 2024

Magnetic hyperthermia therapy (MHT) is a re-emerging treatment modality for brain tumors where magnetic nanoparticles (MNPs) are locally delivered to the brain and then activated with an external alternating magnetic field (AMF) to generate localized heat at a site of interest. Due to the recent advancements in technology and theory surrounding the intervention, clinical and pre-clinical trials have demonstrated that MHT may enhance the effectiveness of chemotherapy and radiation therapy (RT) for the treatment of brain tumors. The future clinical success of MHT relies heavily on designing MNPs optimized for both heating and imaging, developing reliable methods for the local delivery of MNPs, and designing AMF systems with integrated magnetic particle imaging (MPI) for use in humans. However, despite the progression of technological development, the clinical progress of MHT has been underwhelming. This review aims to summarize the current state-of-the-art of MHT and offers insight into the current barriers and potential solutions for moving MHT forward.
Excipients in Pharmaceutical Additive Manufacturing: A Comprehensive Exploration of Polymeric Material Selection for Enhanced 3D Printing
Authors: Muehlenfeld Christian , Duffy Patrick , Yang Fengyuan , Zermeño Pérez David , El-Saleh Firas , Durig Thomas
Published: February 2024

This review provides a comprehensive overview of additive manufacturing (AM) or 3D-printing (3DP) applications in the pharmaceutical industry, with a particular focus on the critical role of polymer selection. By providing insights into how material properties influence the 3DP process and the quality of the final product, this review aims to contribute to a better understanding of the interplay between polymers and pharmaceutical 3DP. As 3DP technologies are increasingly integrated into pharmaceutical sciences, this review contributes insights into the nuanced process of polymer selection, serving mainly as a foundational guide for researchers and formulators new to the subject seeking to harness the full potential of pharmaceutical 3DP by understanding the physicochemical properties, roles, and functions of used polymers in 3D-printed dosage forms and medical devices.
The Development and Characterization of Novel Ionic Liquids Based on Mono- and Dicarboxylates with Meglumine for Drug Solubilizers and Skin Permeation Enhancers
Authors: Furuishi Takayuki , Taguchi Sara , Wang Siran , Fukuzawa Kaori , Yonemochi Etsuo
Published: February 2024

In this study, we synthesized a family of novel ionic liquids (ILs) with meglumine (MGM) as cations and tartaric acid (TA), azelaic acid (AA), geranic acid (GA), and capric acid (CPA) as anions, using pharmaceutical additives via simple acid–base neutralization reactions. The successful synthesis was validated by attenuated total reflection–Fourier transform infrared (ATR-FTIR) and powder X-ray diffraction (PXRD). Thermal analysis using differential scanning calorimetry confirmed the glass transition temperature of MGM-ILs to be within the range of −43.4 °C–−13.8 °C. We investigated the solubilization of 15 drugs with varying pKa and partition coefficient (log P) values using these ILs and performed a comparative analysis. Furthermore, we present MGM-IL as a new skin permeation enhancer for the drug model flurbiprofen (FRP). We confirmed that AA/MGM-IL improves the skin permeation of FRP through hairless mouse skin. Moreover, AA/MGM-IL enhanced drug skin permeability by affecting keratin rather than stratum corneum lipids, as confirmed by ATR-FTIR. To conclude, MGM-ILs exhibited potential as drug solubilizer and skin permeation enhancers of drugs.
Formulation Development of Solid Self-Nanoemulsifying Drug Delivery Systems of Quetiapine Fumarate via Hot-Melt Extrusion Technology: Optimization Using Central Composite Design
Authors: Uttreja Prateek , Youssef Ahmed Adel Ali , Karnik Indrajeet , Sanil Kavish , Narala Nagarjuna , Wang Honghe , Elkanayati Rasha M. , Vemula Sateesh Kumar , Repka Michael A.
Published: February 2024

Quetiapine fumarate (QTF) was approved for the treatment of schizophrenia and acute manic episodes. QTF can also be used as an adjunctive treatment for major depressive disorders. QTF oral bioavailability is limited due to its poor aqueous solubility and pre-systemic metabolism. The objective of the current investigation was the formulation development and manufacturing of solid self-nanoemulsifying drug delivery system (S-SNEDDS) formulation through a single-step continuous hot-melt extrusion (HME) process to address these drawbacks. In this study, Capmul® MCM, Gelucire® 48/16, and propylene glycol were selected as oil, surfactant, and co-surfactant, respectively, for the preparation of S-SNEDDS. Soluplus® and Klucel™ EF (1:1) were selected as the solid carrier. Response surface methodology in the form of central composite design (CCD) was utilized in the current experimental design to develop the S-SNEDDS formulations via a continuous HME technology. The developed formulations were evaluated for self-emulsifying properties, particle size distribution, thermal behavior, crystallinity, morphology, physicochemical incompatibility, accelerated stability, and in vitro drug release studies. The globule size and emulsification time of the optimized SNEDDS formulation was 92.27 ± 3.4 nm and 3.4 ± 3.38 min. The differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) studies revealed the amorphous nature of the drug within the formulation. There were no drug-excipient incompatibilities observed following the Fourier transform infrared (FTIR) spectroscopy. The optimized formulation showed an extended-release profile for 24 h. The optimized formulation was stable for three months (last time-point tested) at 40 °C/75% RH. Therefore, the developed S-SNEDDS formulation could be an effective oral delivery platform for QTF and could lead to better therapeutic outcomes.
Research Progress of Extracellular Vesicles-Loaded Microneedle Technology
Authors: Wang Xue , Cheng Wei , Su Jiandong
Published: February 2024

Microneedles (MNs), renowned for their painless and minimally invasive qualities, exhibit significant potential for facilitating effective drug delivery, vaccination, and targeted sample extraction. Extracellular vesicles (EVs), serving as cargo for MNs, are naturally occurring nanovesicles secreted by cells and characterized by novel biomarkers, low immunogenicity, and cell-source-specific traits. MNs prove instrumental in extracting EVs from the sample fluid, thereby facilitating a promising diagnostic and prognostic tool. To harness the therapeutic potential of EVs in tissue repair, MNs with sustained delivery of EVs leverage micron-sized channels to enhance targeted site concentration, demonstrating efficacy in treating various diseases, such as Achillea tendinopathy, hair loss, spinal cord injury, and diabetic ulcers. EV-loaded MNs emerge as a promising platform for repair applications of skin, cardiac, tendon, hair, and spinal cord tissues. This review commences with an overview of MNs, subsequently delving into the role of EVs as cargo for MNs. The paper then synthesizes the latest advancements in the use of EV-loaded MNs for tissue regenerative repair, extending to research progress in extracting EVs from MNs for disease diagnosis and prognostic evaluations. It aims to offer valuable insights and forecast future research trajectories with the hope of inspiring innovative ideas among researchers in this field.
Design Space and Control Strategy for the Manufacturing of Wet Media Milled Drug Nanocrystal Suspensions by Adopting Mechanistic Process Modeling
Authors: Bitterlich André , Mihorko Andrej , Juhnke Michael
Published: February 2024

Wet media milling is a fully industrialized technology for the manufacturing of drug nanocrystal suspensions. This work describes the development of an advanced control strategy and an associated design space for a manufacturing process at a commercial scale. Full-scale experiments and mechanistic process modeling have been used to establish a physically reasonable control strategy of factors relevant to the quality attributes of the nanocrystal suspension. The design space has been developed based on a mature mechanistic process model of the wet media milling procedure. It presents the process–product attribute relationship between a multidimensional range of measured process parameters and a range of the product-quality attribute mean particle sizes. The control strategy allows for simple, robust, and sound scientific process control as well as the operational flexibility of the suspension batch size. This is an industrial case study of control strategy and design-space definition with the crucial contribution of mechanistic process modeling for an intended commercial manufacturing process.
A Critique of the Inclusion/Exclusion Dichotomy
Authors: Felix Cathrine Victoria
Published: February 2024

In contemporary discourse, inclusion has evolved into a core value, with inclusive societies being lauded as progressive and inherently positive. Conversely, exclusion and excluding practices are typically deemed undesirable. However, this paper questions the prevailing assumption that inclusion is always synonymous with societal progress. Could it be that exclusion, in certain contexts, serves as a more effective tool for advancing societal development? Is there a more intricate interconnection between these phenomena than conventionally acknowledged? This paper advocates moving beyond a simplistic inclusion/exclusion dichotomy and puts forth two theses. First, it posits that exclusion can, at times, be a superior metric for gauging progress. Second, it contends that inclusion and exclusion are thoroughly entwined, challenging the notion of a clear demarcation between them. The underlying premise is that, much like inclusion, there can be meaningful value associated with exclusion. Furthermore, applying a rigid inclusion/exclusion dichotomy oversimplifies the discourse on societal progress, providing an artificial representation of what constitutes advancement. Such oversimplification hampers both contemporary research in the humanities and broader political discourse. The primary objective of this paper is to introduce a fresh perspective to the discourse surrounding societal progress. By challenging the fundamental conceptual framework, it seeks to add nuance to the ongoing debate, fostering a more comprehensive understanding of the complexities inherent in measuring progress within society.
GeAsSeTe/GeAsSe Pedestal Waveguides for Long-Wave Infrared Tunable on-Chip Spectroscopy
Authors: Mourgelas Vasileios , Boonsit Sirawit , Wilkinson James Shafto , Senthil Murugan Ganapathy
Published: February 2024

A dry-etched pedestal chalcogenide waveguide platform, designed for use in long-wave IR spectrometer applications, is demonstrated, fabricated and optically characterized. The optical layers were deposited on pre-patterned dry-etched silicon pedestals. An exceptionally low waveguide propagation loss was measured, at around 0.1 dB/cm at λ = 10 μm. The modal thermo-optic coefficient of the waveguide was experimentally estimated to be approximately 1.1 × 10−4 C−1 at λ = 1.63 μm, which is comparable to that of Si and GaAs. Waveguide spiral interferometers were fabricated, proving the potential for realization of more complex, chalcogenide-based, integrated photonic circuits. The combination of low propagation losses and a strong thermo-optic coefficient makes this platform an ideal candidate for utilization in on-chip tunable spectrometers in the long-wave IR wavelength band.
An InGaAs Vertical-Cavity Surface-Emitting Laser Emitting at 1130 nm for Silicon Photonics Application
Authors: Fang Yunfeng , Zhang Yang , Li Chuanchuan , Li Jian , Wang Yongli , Wei Xin
Published: February 2024

A highly strained InGaAs quantum well (QW) vertical-cavity surface-emitting laser (VCSEL) with low threshold current density, high efficiency and output power emissions around 1130 nm was grown by MOCVD. Its static characteristics at room temperature and high operation temperature were studied in detail. The 7 μm oxide aperture device exhibits a threshold current of 0.68 mA, corresponding to a threshold current density of 1.7 kA/cm2. The slope efficiency is 0.43 W/A and the maximum output power is 3.3 mW. Continuous-wave (CW) operation in the 10–80 °C temperature range is observed. The slope efficiency is almost constant at 10–80 °C. The threshold current becomes lower at high temperatures thanks to the alignment between gain peak and cavity mode. The 3 μm oxide aperture device’s lasing in single mode with the RMS spectral width of 0.163 nm and orthogonal polarization suppression ratio (OPSR) is ~15 dB at 25 °C. The small-signal response analysis indicates that reducing the parasitics of the device and refining the fabrication process will improve the dynamics response characteristics. These results indicate that the 1130 nm GaAs-based VCSEL with highly strained InGaAs QWs is expected to be used as source for silicon photonics.