bluuebunny/crossref_metadata_2025 huggingface dataset:
UK Chickpea Consumption Doubled from 2008/09–2018/19
Authors: Kutepova Inga , Rehm Colin D. , Friend Samara Joy
Published: November 2023

Background: Only 9% of individuals in the United Kingdom (UK) meet the recommendation for dietary fibre intake. Little is known about chickpea consumption in the UK. Methods: Chickpea intake trends and sociodemographic patterns were analysed using the National Diet and Nutrition Survey Rolling Programme data collected from 2008/09 to 2018/19 among 15,655 individuals ≥1.5 years completing a four-day food diary. Chickpea consumers were identified based on a list of chickpea-containing foods, with the most consumed foods being hummus, boiled chickpeas, chickpea flour, and low/reduced-fat hummus. Micronutrient and food group intakes were compared between chickpea consumers and non-consumers; the Modified Healthy Dietary Score was also assessed, which measures adherence to UK dietary recommendations. Results: Chickpea consumption increased from 6.1% (2008–2012) to 12.3% (2016–2019). Among 1.5–3 years, consumption increased from 5.7% to 13.4%, and among 19–64 years, consumption increased from 7.1% to 14.4%. The percentage of individuals eating chickpeas was higher among individuals with higher incomes and more education. Healthy-weight adults were more likely to consume chickpeas compared to those who were overweight or obese. Compared to both bean and non-bean consumers, chickpea consumers ate significantly more dietary fibre, fruits and vegetables, pulses, nuts, and less red meat and processed meat products. Chickpea consumers also had a higher Modified Healthy Dietary Score. Conclusions: In the UK, chickpea consumption more than doubled from 2008/09 to 2018/19. Chickpea consumers had a higher diet quality than non-consumers.
Role of Baseline Gut Microbiota on Response to Fiber Intervention in Individuals with Irritable Bowel Syndrome
Authors: Zhou Jerry , Ho Vincent
Published: November 2023

Irritable bowel syndrome (IBS) is one of the most prevalent functional gut disorders in the world. Partially hydrolyzed guar gum, a low-viscosity soluble fiber, has shown promise in the management of IBS-related symptoms. In this study, we aimed to determine if an individual’s baseline gut microbiota impacted their response to a partially hydrolyzed guar gum intervention. Patients diagnosed with IBS undertook a 90-day intervention and follow-up. IBS symptom severity, tolerability, quality-of-life, and fecal microbiome composition were recorded during this study. Patients with normal microbiota diversity (Shannon index ≥ 3) showed significant improvements to IBS symptom scores, quality-of-life, and better tolerated the intervention compared to patients with low microbiota diversity (Shannon index < 3). Our findings suggest that an individual’s baseline microbiome composition exerts a substantial influence on their response to fiber intervention. Future investigations should explore a symbiotic approach to the treatment of IBS.
The Role of Polyunsaturated Fatty Acids in Osteoarthritis: Insights from a Mendelian Randomization Study
Authors: Li Xuefei , Lu Zhengjie , Qi Yongjian , Chen Biao , Li Bin
Published: November 2023

The prior observational research on the impact of polyunsaturated fatty acid (PUFA) supplementation on osteoarthritis (OA) patients had yielded inclusive outcomes. This study utilized the Mendelian randomization (MR) approach to explore potential causal relationships between PUFAs and OA. The MR study was performed using GWAS summary statistics for PUFAs, encompassing omega-3 and omega-6 fatty acids, and for knee OA (KOA) and hip OA (HOA). The primary inverse-variance-weighted (IVW) method and two supplementary MR approaches were used to establish robust causality. Heterogeneity and horizontal pleiotropy were assessed using Cochrane’s Q and MR-Egger intercept tests. Additionally, a range of sensitivity analyses were conducted to strengthen the precision and reliability of the results. The IVW method indicated a potential genetic association between omega-3 fatty acids and KOA risk (odd ratio (OR) = 0.94, 95% confidence interval (CI): 0.89–1.00, p = 0.048). No significant correlation was found between omega-3 levels and HOA. Moreover, genetically predicted higher levels of omega-6 fatty acids were associated with a decreased risk of KOA (OR = 0. 93, 95% CI: 0.86–1.00, p = 0.041) and HOA (OR = 0.89, 95% CI: 0.82–0.96; p = 0.003). The MR-Egger intercept evaluation showed no horizontal pleiotropy affecting the MR analysis (all p  >  0.05). Our findings supported the causal relationship between PUFAs and OA susceptibility and offered a novel insight that high omega-6 fatty acids may reduce the risk of KOA and HOA. These results underscore the importance of maintaining optimal levels of PUFAs, particularly omega-6 fatty acids, in individuals with a genetic predisposition to OA. Future research is necessary to validate these findings and elucidate the underlying mechanisms involved.
Maternal Body Mass Index Trends and Weight Gain in Singleton Pregnancies at the Time of Fetal Anatomic Survey: Changes in the Last Decade and New Trends in the Modern Era
Authors: Ursache Alexandra , Bujor Iuliana Elena , Cristofor Alexandra Elena , Zelinschi Denisa Oana , Nemescu Dragos , Matasariu Daniela Roxana
Published: November 2023

(1) Background: the worldwide impact of overweight and obesity is rising, increasingly resembling an epidemic (a price we have to pay for our new way of living). (2) Methods: our study aims to evaluate the temporal trends and patterns of singleton pregnant women’s BMI (body mass index) in our region during a 12-year time frame between 2010 and 2021. (3) Results: We noticed a statistically significant difference between the BMIs of nulliparous and multiparous women and a significantly increased pregestational BMI in women with previous ART (assisted reproductive technology) procedures. Smoking pregnant women had a higher second trimester weight gain, regardless of parity. Women with folic acid supplementation alone had a higher BMI than those with folic acid and multivitamin intake. The weight of both nulliparous and multiparous women with chronic hypertension was statistically significantly higher in all three timeframes. Global weight gain did not reveal any statistically significant changes concerning women with pregestational diabetes, regardless of parity and the pregnancy trimester. (4) Conclusions: our article describes the trends in obesity and overweight in our middle-income country, in which this pathology is continuously growing, negatively influencing our reproductive-aged women and future generations.
Relationship between Iron Deficiency and Thyroid Function: A Systematic Review and Meta-Analysis
Authors: Garofalo Vincenzo , Condorelli Rosita A. , Cannarella Rossella , Aversa Antonio , Calogero Aldo E. , La Vignera Sandro
Published: November 2023

Objective: Iron deficiency (ID) is the most prevalent nutritional deficiency worldwide. Low levels of serum ferritin (SF) could affect the thyroid gland and its functioning. The purpose of this systematic review and meta-analysis is to summarize the main currently available evidence and analyze data on the relationship between ID and thyroid function. Methods: This study included all articles evaluating the relationship between ID and thyroid function. Quality assessment was performed using Cambridge Quality Checklists. The search strategy included the following combination of Medical Subjects Headings terms and keywords: “iron deficiency”, “thyroid function”, “thyroid disease”, “thyroid dysfunction”, and “hypothyroidism”. A meta-analysis was performed to evaluate whether thyroid stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) levels differed between patients with ID and healthy controls without ID. For statistical comparison between cases and controls, the mean difference (MD) was calculated, and a subgroup analysis of pregnant and non-pregnant women was performed. Cochran’s Q testing and heterogeneity indices (I2) were used to assess statistical heterogeneity. Sensitivity analysis and publication bias analyses were also performed, both qualitatively and quantitatively. Finally, a meta-regression analysis was performed to evaluate the correlation between serum TSH or FT4 levels and SF in the study population. Results: Ten cross-sectional studies were identified and reviewed. Patients with ID showed TSH (MD: −0.24 mIU/L; 95% CI −0.41, −0.07; I2 = 100%, p = 0.005), FT4 (MD: −1.18 pmol/L; 95% CI −1.43, −0.94; I2 = 99%, p < 0.000001), and FT3 (MD: −0.22 pmol/L; 95% CI −0.32, −0.12; I2 = 99%, p < 0.00001) levels that were significantly lower. Subgroup analysis confirmed significantly lower TSH, FT4, and FT3 levels in pregnant women. Non-pregnant women showed significantly lower serum FT4 and FT3 levels but no difference in TSH values. Meta-regression analysis showed that serum TSH and FT4 levels were positively correlated with SF levels. Our systematic review of the literature found that ID significantly increases the prevalence of thyroid autoantibody (anti-thyroglobulin antibodies and anti-thyroid peroxidase antibodies) positivity both individually and collectively. Conclusion: Studies currently published in the literature indicate a possible relationship between ID, thyroid function, and autoimmunity, especially in some patient groups. Data analysis shows that thyroid hormone levels are lower in patients with ID and, in particular, in pregnant women. Further studies are needed to understand the role played by iron in thyroid metabolism.
Association between Total Dietary Phytochemical Intake and Cardiometabolic Health Outcomes—Results from a 10-Year Follow-Up on a Middle-Aged Cohort Population
Authors: Gamba Magda , Pano Octavio , Raguindin Peter Francis , Roa-Diaz Zayne M. , Muka Taulant , Glisic Marija , Franco Oscar H. , Marques-Vidal Pedro
Published: November 2023

Dietary phytochemical intake associations with cardiovascular health and mortality remain unknown. We studied the relations between total dietary phytochemical intake and cardiovascular health outcomes in a middle-aged Swiss population. We analyzed data spanning 2009 to 2021 from a prospective cohort study in Lausanne, Switzerland, including 3721 participants (54.8% women, 57.2 ± 10.3 years) without cardiovascular disease (CVD) history. Dietary intake was assessed using a validated self-reported food frequency questionnaire. The Dietary Phytochemical Index (DPI) and the healthy Dietary Phytochemical Index (hDPI) were calculated as the total energy intake percentage obtained from phytochemical-rich food consumption. The Healthy Plant-Based Diet Index (hPBD) was estimated by scoring healthy plant foods positively and less-healthy plant foods negatively. Indices tertiles and cardiometabolic outcome associations were determined using Cox proportional hazard models. Over 30,217 person-years of follow-up, 262 CVD events, and 178 deaths occurred. Unadjusted analyses found 36%, 33%, and 32% lower CVD risk for the highest hDPI, DPI, and hPBD tertiles, respectively. After adjustment, only the second hDPI tertile showed a 30% lower CVD risk (HR 0.70, 95% CI 0.51–0.95; P for trend 0.362). No other associations emerged. In this middle-aged Swiss cohort, no associations between dietary indices reflecting a phytochemical-rich dietary pattern and incident CVD, all-cause, or CVD mortality were observed.
Production of Proinflammatory Cytokines by CD4+ and CD8+ T Cells in Response to Mycobacterial Antigens among Children and Adults with Tuberculosis
Authors: Morrow Erin , Liu Qijia , Kiguli Sarah , Swarbrick Gwendolyn , Nsereko Mary , Null Megan D. , Cansler Meghan , Mayanja-Kizza Harriet , Boom W. Henry , Chheng Phalkun , Nyendak Melissa R. , Lewinsohn David M. , Lewinsohn Deborah A. , Lancioni Christina L.
Published: November 2023

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a leading cause of pediatric morbidity and mortality. Young children are at high risk of TB following Mtb exposure, and this vulnerability is secondary to insufficient host immunity during early life. Our primary objective was to compare CD4+ and CD8+ T-cell production of proinflammatory cytokines IFN-gamma, IL-2, and TNF-alpha in response to six mycobacterial antigens and superantigen staphylococcal enterotoxin B (SEB) between Ugandan adults with confirmed TB (n = 41) and young Ugandan children with confirmed (n = 12) and unconfirmed TB (n = 41), as well as non-TB lower respiratory tract infection (n = 39). Flow cytometry was utilized to identify and quantify CD4+ and CD8+ T-cell cytokine production in response to each mycobacterial antigen and SEB. We found that the frequency of CD4+ and CD8+ T-cell production of cytokines in response to SEB was reduced in all pediatric cohorts when compared to adults. However, T-cell responses to Mtb-specific antigens ESAT6 and CFP10 were equivalent between children and adults with confirmed TB. In contrast, cytokine production in response to ESAT6 and CFP10 was limited in children with unconfirmed TB and absent in children with non-TB lower respiratory tract infection. Of the five additional mycobacterial antigens tested, PE3 and PPE15 were broadly recognized regardless of TB disease classification and age. Children with confirmed TB exhibited robust proinflammatory CD4+ and CD8+ T-cell responses to Mtb-specific antigens prior to the initiation of TB treatment. Our findings suggest that adaptive proinflammatory immune responses to Mtb, characterized by T-cell production of IFN-gamma, IL-2, and TNF-alpha, are not impaired during early life.
Major Pathogens Affecting Carob in the Mediterranean Basin: Current Knowledge and Outlook in Italy
Authors: Castello Ivana , Polizzi Giancarlo , Vitale Alessandro
Published: November 2023

The main pathogens affecting the carob (Ceratonia siliqua) tree in the Mediterranean basin are described in this overview. The most widespread diseases periodically occurring in carob orchards are powdery mildew (Pseudoidium ceratoniae) and cercospora leaf spot (Pseudocercospora ceratoniae). The causal agents of “black leaf spots” (e.g., Pestalotiopsis, Phyllosticta and Septoria spp.) are responsible for symptoms similar to those previously mentioned for foliar diseases, but are reported in carob orchards at a negligible frequency. Likewise, canker and branch diebacks caused by fungal species belonging to Botryosphaeriaceae are almost never recorded. Among the rots of wood tissues that may compromise old carob specimens, “brown cubical rot” caused by Laetiporus sulphureus is the most widespread and recurrent issue; this pathogen is also well-known for producing edible fruit bodies that are appreciated for pharmaceutical and industrial purposes. On the other hand, “white rots” caused by Fomes and Ganoderma species are less common and reported for the first time in this review. Gall-like protuberances on twigs of uncertain aetiology or tumors on branches associated with Rhizobium radiobacter are described, although these symptoms are seldom detected, as they are also observed for necrotic leaf spots caused by Pseudomonas syringae pv. ciccaronei. A worldwide list of pathogens not yet recorded but at high risk of potential introduction in Italian carob-producing areas is also provided. Finally, concerns related to new phytopathogenic fungi vectored by the invasive Xylosandrus compactus ambrosia beetle are addressed. All the described pathogens could become limiting factors for carob production in the near future, because they could be favored by high-density orchards, the increasing global network of trade exchanges, and the high frequency at which extreme events related to climate change occur globally. Thus, symptoms and signs, causal agents, epidemiology, and, whenever applicable, recommendations for disease prevention and management are provided in this review.
Molecular Characterization of Hetero-Pathogenic and Diarrheagenic Escherichia coli Pathotypes in Diarrheic Children under Five Years and Exposure Environment in Ogun State, South-West Nigeria
Authors: Ogunbiyi Tosin Segun , Fayemi Olanrewaju Emmanuel , Akanni Gabriel Bidemi , Ayolabi Christianah Idowu , Hald Tine
Published: November 2023

Background: Diarrheagenic Escherichia coli (DEC) is one of the most common etiological agents of moderate-to-severe diarrhea in Low- and Middle-Income Countries (LMICs). Therefore, determining the source(s) of DEC in index cases and exposure environment is important for developing a prevention strategy. The current study aims to investigate the prevalence of DEC among children under 5 years and their exposure environment in Ogun State, Nigeria. Methods: Samples from 228 diarrheic children and their exposure environment were collected and screened for E. coli. Bio-chemically compatible distinct colonies were molecularly characterized using a 7-virulence-gene multiplex PCR with virulence factors (VFs) indicative of four pathotypes of E. coli: enterotoxigenic (ETEC), verotoxigenic (VTEC), enteropathogenic (EPEC), and enteroinvasive (EIEC). Representative pathotypes were subjected to antimicrobial susceptibility and over-expressed efflux pump assays. Results: One or more VFs typical of specific pathotypes were detected in 25.9% (59/228) diarrhea cases consisting of ETEC (21.5%) and EPEC (0.4%), while hetero-pathogenic pathotypes were found in 4.0% of cases. Of the food sources, 27.9% (101/362) were positive for DEC, of which ETEC accounted for 21.0%, VTEC 1.9%, EPEC 0.6%, EIEC 0.6%, and hetero-pathogenic pathotypes were 3.9%. Furthermore, ETEC was the only pathotype detected in the wastewater (4/183). Interestingly, the consumption of street-vended foods was the most significant (p = 0.04) risk factor for DEC infection in the study area. A total of 73.3% of selected DEC pathotypes showed resistance to antimicrobials, while 27.5% demonstrated over-expression of efflux pump activity. Conclusion: The high prevalence of ETEC across all sources and the occurrence of hetero-pathogenic DEC in diarrheic children and food sources emphasizes the importance of establishing a better strategy for the control and prevention of diarrhea among children in low- and medium-income households.
Molecular Epidemiology and Genetic Diversity of the Enteric Protozoan Parasite Blastocystis sp. in the Northern Egypt Population
Authors: Naguib Doaa , Gantois Nausicaa , Desramaut Jeremy , Arafat Nagah , Mandour Mohamed , Abdelmaogood Asmaa Kamal Kamal , Mosa Ashraf Fawzy , Denoyelle Constance , Even Gaël , Certad Gabriela , Chabé Magali , Viscogliosi Eric
Published: November 2023

Blastocystis sp. is currently reported as the most frequent single-celled eukaryote inhabiting the intestinal tract of humans and a wide range of animal groups. Its prevalence is especially higher in developing countries linked with fecal peril. Despite a growing interest in this enteric protozoan, certain geographical regions potentially at high risk of infection, such as North Africa, remain under-investigated. Therefore, a large-scale molecular epidemiological survey, including 825 participants presenting digestive disorders or not, was conducted in five governorates located in Northern Egypt. A real-time polymerase chain reaction (qPCR) assay was performed to identify the parasite in stool samples, followed by direct sequencing of the positive PCR products for subtyping and genotyping of the corresponding isolates. The overall prevalence was shown to reach 72.4% in the Egyptian cohort, coupled with a variable frequency depending on the governorate (41.3 to 100%). Among the 597 positive participants, a large proportion of them (39.4%) presented mixed infections, as determined by sequencing. The remaining individuals with single infection were predominantly colonized by subtype 3 (ST3) (48.3%) followed by ST1 (39.5%), ST2 (10.8%), ST14 (1.1%), and ST10 (0.3%). This was the first report of ST10 and ST14 in North Africa. Age, sex, digestive symptoms, and health status of the participants or contact with animals were not identified as significant risk factors for Blastocystis sp. occurrence or affecting the ST distribution. In contrast, substantial variations in the prevalence and ST distribution of the parasite were reported according to the governorate. Genotyping of isolates revealed the lower intra-ST diversity for ST3, followed by ST1 and then ST2. By combining subtyping and genotyping data, a widespread inter-human transmission was strongly suggested for ST3 within the Egyptian cohort. Regarding ST1 and ST2, additional animal or environmental sources of infection by these STs have been proposed, whereas the few cases of colonization by ST10 and ST14 were likely the result of zoonotic transmission from bovid. These investigations clearly emphasized the active circulation of Blastocystis sp. in Northern Egypt and the necessity for health authorities to implement prevention campaigns towards the population and quality control of drinking water, with the aim of reducing the burden of this enteric protozoan in this endemic country.
Comprehensive Observational Study in a Large Cohort of Asthma Patients after Adding LAMA to ICS/LABA
Authors: Plaza Vicente , Domínguez-Ortega Javier , González-Segura Alsina Diego , Lo Re Daniele , Sicras-Mainar Antoni
Published: November 2023

Introduction: Adding LAMA to LABA/ICS is recommended to improve control in patients with persistent asthma. Methods: This observational, retrospective, before-and-after study considered patients diagnosed with asthma who started LABA/ICS + LAMA treatment (triple therapy, TT) between 1 January 2017 and 31 December 2018 and had been treated with LABA/ICS (dual therapy, DT) in the year before. Changes in lung function and exacerbation rates, healthcare resource utilization, and healthcare and non-healthcare costs (€2019) were estimated in patients with asthma in clinical practices in Spain. Data from computerized medical records from seven Spanish regions were collected ±1 year of LAMA addition. Results: 4740 patients (64.1 years old [SD: 16.3]) were included. TT reduced the incidence of exacerbations by 16.7% (p < 0.044) and the number of patients with exacerbations by 8.5% (p < 0.001) compared to previous DT. The rate of patients with severe exacerbations requiring systemic corticosteroids and their hospitalization rates significantly decreased by 22.5% and 29.5%. TT significantly improved FEV1, FVC, and FEV1/FVC, saving €571/patient for society. Younger patients with asthma (18–44 years old) and patients with severe asthma (FEV1 < 60%) performed better upon the initiation of TT. Conclusions: TT reduced asthma exacerbations, improved lung function and reduced healthcare costs vs. DT, particularly in patients requiring systemic corticosteroids to treat severe exacerbations.
Skin Toxicities Associated with Botulin Toxin Injection for Aesthetic Procedures: Data from the European Spontaneous Reporting System
Authors: Nicoletti Maria Maddalena , Anatriello Antonietta , Liguori Valerio , Cantone Andrea , di Mauro Gabriella , Izzo Imma , Lettera Nicoletta , Della Ragione Joao Marcos , Campitiello Maria Rosaria , Cosenza Vincenzo , Scavone Cristina
Published: November 2023

Botulinum toxin is a protein deriving from the bacteria Clostridium botulinum and it is widely used for the treatment of a variety of muscle hyperactivity syndromes and for cosmetic indications. Having a long-lasting effect, Botulinum toxin type A (BTA) is one of the most botulin toxin products used. Even if BTA has shown benefits in reducing the vertical lines between the eyebrows, Adverse Drug Reactions (ADRs) have been experienced as well, of which the most common ones are headache and drooping eyelids. In addition, since other local and systemic risks have been identified, a non-interventional post-authorization safety study (PASS) has been started. The aim of the present study was to report cases of skin toxicity associated with this drug, considering Individual Case Safety Reports (ICSRs) existing on the Eudravigilance website. Among 1464 ICSRs sent to the EV database, 718 ICSRs, including 5154 PTs, reported BTA as a suspected drug associated with cutaneous toxicity. The majority of patients experiencing BTA-induced skin toxicity were female (92.1%) belonging mostly to the age group of 18–64 years. The most serious criteria, when reported, were “Other Medically Important Condition” and “Caused/prolonged hospitalization”, although the outcome was mainly reported as “Unknown”. The most reported PTs, related to skin disorders, were: “Erythema”, “Rash”, “Pruritus”, “Urticaria”, “Swelling face”, “Brow ptosis”, “Eyelid ptosis”, “Injection site pain”, and “Angioedema”. Considering that in most ICSRs, ADRs related to skin disorders were symptoms of hypersensitivity reactions which in some conditions could be life-threatening, further studies are required to better define the safety profile of BTA used for aesthetic procedures.
The Metabolic Fingerprint of Doxorubicin-Induced Cardiotoxicity in Male CD-1 Mice Fades Away with Time While Autophagy Increases
Authors: Brandão Sofia Reis , Reis-Mendes Ana , Neuparth Maria João , Carvalho Félix , Ferreira Rita , Costa Vera Marisa
Published: November 2023

The cardiotoxicity of doxorubicin (DOX) may manifest at the beginning/during treatment or years after, compromising patients’ quality of life. We intended to study the cardiac pathways one week (short-term, control 1 [CTRL1] and DOX1 groups) or five months (long-term, CTRL2 and DOX2 groups) after DOX administration in adult male CD-1 mice. Control groups were given saline, and DOX groups received a 9.0 mg/Kg cumulative dose. In the short-term, DOX decreased the content of AMP-activated protein kinase (AMPK) while the electron transfer flavoprotein-ubiquinone oxidoreductase (ETF-QO) increased compared to CTRL1, suggesting the upregulation of fatty acids oxidation. Moreover, mitofusin1 (Mfn1) content was decreased in DOX1, highlighting decreased mitochondrial fusion. In addition, increased B-cell lymphoma-2 associated X-protein (BAX) content in DOX1 pointed to the upregulation of apoptosis. Conversely, in the long-term, DOX decreased the citrate synthase (CS) activity and the content of Beclin1 and autophagy protein 5 (ATG5) compared to CTRL2, suggesting decreased mitochondrial density and autophagy. Our study demonstrates that molecular mechanisms elicited by DOX are modulated at different extents over time, supporting the differences on clinic cardiotoxic manifestations with time. Moreover, even five months after DOX administration, meaningful heart molecular changes occurred, reinforcing the need for the continuous cardiac monitoring of patients and determination of earlier biomarkers before clinical cardiotoxicity is set.
A Review of Childhood Acute Myeloid Leukemia: Diagnosis and Novel Treatment
Authors: Tseng Serena , Lee Mu-En , Lin Pei-Chin
Published: November 2023

Acute myeloid leukemia (AML) is the second most common hematologic malignancy in children. The incidence of childhood AML is much lower than acute lymphoblastic leukemia (ALL), which makes childhood AML a rare disease in children. The role of genetic abnormalities in AML classification, management, and prognosis prediction is much more important than before. Disease classifications and risk group classifications, such as the WHO classification, the international consensus classification (ICC), and the European LeukemiaNet (ELN) classification, were revised in 2022. The application of the new information in childhood AML will be upcoming in the next few years. The frequency of each genetic abnormality in adult and childhood AML is different; therefore, in this review, we emphasize well-known genetic subtypes in childhood AML, including core-binding factor AML (CBF AML), KMT2Ar (KMT2A/11q23 rearrangement) AML, normal karyotype AML with somatic mutations, unbalanced cytogenetic abnormalities AML, NUP98 11p15/NUP09 rearrangement AML, and acute promyelocytic leukemia (APL). Current risk group classification, the management algorithm in childhood AML, and novel treatment modalities such as targeted therapy, immune therapy, and chimeric antigen receptor (CAR) T-cell therapy are reviewed. Finally, the indications of hematopoietic stem cell transplantation (HSCT) in AML are discussed.
A Rapid Screening Platform for Simultaneous Evaluation of Biodegradation and Therapeutic Release of an Ocular Hydrogel
Authors: Ho Brandon , Phan Chau-Minh , Garg Piyush , Shokrollahi Parvin , Jones Lyndon
Published: November 2023

This study attempts to address the challenge of accurately measuring the degradation of biodegradable hydrogels, which are frequently employed in drug delivery for controlled and sustained release. The traditional method utilizes a mass-loss approach, which is cumbersome and time consuming. The aim of this study was to develop an innovative screening platform using a millifluidic device coupled with automated image analysis to measure the degradation of Gelatin methacrylate (GelMA) and the subsequent release of an entrapped wetting agent, polyvinyl alcohol (PVA). Gel samples were placed within circular wells on a custom millifluidic chip and stained with a red dye for enhanced visualization. A camera module captured time-lapse images of the gels throughout their degradation. An image-analysis algorithm was used to translate the image data into degradation rates. Simultaneously, the eluate from the chip was collected to quantify the amount of GelMA degraded and PVA released at various time points. The visual method was validated by comparing it with the mass-loss approach (R = 0.91), as well as the amount of GelMA eluted (R = 0.97). The degradation of the GelMA gels was also facilitated with matrix metalloproteinases 9. Notably, as the gels degraded, there was an increase in the amount of PVA released. Overall, these results support the use of the screening platform to assess hydrogel degradation and the subsequent release of entrapped therapeutic compounds.
Synthesis and Preclinical Evaluation of Radiolabeled [103Ru]BOLD-100
Authors: Happl Barbara , Brandt Marie , Balber Theresa , Benčurová Katarína , Talip Zeynep , Voegele Alexander , Heffeter Petra , Kandioller Wolfgang , Van der Meulen Nicholas P. , Mitterhauser Markus , Hacker Marcus , Keppler Bernhard K. , Mindt Thomas L.
Published: November 2023

The first-in-class ruthenium-based chemotherapeutic agent BOLD-100 (formerly IT-139, NKP-1339, KP1339) is currently the subject of clinical evaluation for the treatment of gastric, pancreatic, colorectal and bile duct cancer. A radiolabeled version of the compound could present a helpful diagnostic tool. Thus, this study investigated the pharmacokinetics of BOLD-100 in more detail to facilitate the stratification of patients for the therapy. The synthesis of [103Ru]BOLD-100, radiolabeled with carrier added (c.a.) ruthenium-103, was established and the product was characterized by HPLC and UV/Vis spectroscopy. In order to compare the radiolabeled and non-radioactive versions of BOLD-100, both complexes were fully evaluated in vitro and in vivo. The cytotoxicity of the compounds was determined in two colon carcinoma cell lines (HCT116 and CT26) and biodistribution studies were performed in Balb/c mice bearing CT26 allografts over a time period of 72 h post injection (p.i.). We report herein preclinical cytotoxicity and pharmacokinetic data for BOLD-100, which were found to be identical to those of its radiolabeled analog [103Ru]BOLD-100.
In Vitro Assessment of SWEEPS and Antimicrobial Photodynamic Therapy Alone or in Combination for Eradicating Enterococcus faecalis Biofilm in Root Canals
Authors: Shahi Ardakani Ali , Afrasiabi Shima , Sarraf Pegah , Benedicenti Stefano , Solimei Luca , Chiniforush Nasim
Published: November 2023

Objectives: This study investigates the efficacy of antimicrobial photodynamic therapy (aPDT) using riboflavin and a blue diode laser (BDL), combined with shock wave-enhanced emission photoacoustic streaming (SWEEPS), against Enterococcus faecalis. Materials and Methods: A total of 48 extracted single-rooted human teeth were used. The root canals were instrumented, sealed at their apices, had the smear layer removed, and then underwent autoclave sterilization. Subsequently, each canal was inoculated with E. faecalis bacterial suspension and allowed to incubate for ten days. After confirming the presence of biofilms through scanning electron microscopy (SEM) in three teeth, the remaining teeth were randomly allocated into nine groups, each containing five teeth: control, 5.25% sodium hypochlorite (NaOCl), BDL, SWEEPS + normal saline, SWEEPS + NaOCl, riboflavin, riboflavin + SWEEPS, riboflavin + BDL, and riboflavin + BDL + SWEEPS. After the treatment, the numbers of colony-forming units (CFUs)/mL were calculated. The data were analysed using one-way ANOVA followed by Tukey’s test for comparisons. Results: All groups, with the exception of the BDL group, exhibited a significant reduction in E. faecalis CFU/mL when compared to the control group (p < 0.001). The difference in CFU/mL value between riboflavin + BDL + SWEEPS and riboflavin + SWEEPS was significant (p = 0.029), whereas there was no significant difference between riboflavin + BDL + SWEEPS and riboflavin + BDL (p = 0.397). Moreover, there was no statistically significant difference between the riboflavin + SWEEPS group and the riboflavin + BDL group (p = 0.893). Conclusions: The results demonstrated that combining the SWEEPS technique with riboflavin as a photosensitizer activated by BDL in aPDT effectively reduced the presence of E. faecalis in root canals.
The Ectomycorrhizal Fungi and Soil Bacterial Communities of the Five Typical Tree Species in the Junzifeng National Nature Reserve, Southeast China
Authors: Pang Wenbo , Zhang Panpan , Zhang Yuhu , Zhang Xiao , Huang Yanbin , Zhang Taoxiang , Liu Bao
Published: November 2023

To explore the contribution of microorganisms to forest ecosystem function, we studied the ectomycorrhizal (ECM) fungal and soil bacterial community of the five typical tree species (Pinus massoniana, PM; Castanopsis carlesii, CC; Castanopsis eyrei, CE; Castanopsis fargesii, CF; and Keteleeria cyclolepis, KC) at the Junzifeng National Nature Reserve. The results indicated that the ECM fungal and soil bacterial diversity of CC and CF was similar, and the diversity rates of CC and CF were higher than those of PM, CE, and KC. Cenococcum geophilum and unclassified_Cortinariaceae II were the most prevalent occurring ECM fungi species in the five typical tree species, followed by unclassified_Cortinariaceae I and Lactarius atrofuscus. In bacteria, the dominant bacterial genera were Acidothermus, Bradyrhizobium, Acidibacter, Candidatus_Solibacter, Candidatus_Koribacter, Roseiarcus, and Bryobacter. EMF fungi and soil bacteria were correlated with edaphic factors, especially the soil pH, TP, and TK, caused by stand development. The results show that the community characteristics of ECM fungi and bacteria in the typical tree species of the Junzifeng National Nature Reserve reflect the critical role of soil microorganisms in stabilizing forest ecosystems.
Fungal Pathogens of Cacao in Puerto Rico
Authors: Puig Alina Sandra
Published: November 2023

Cacao production is a rapidly expanding industry in Puerto Rico, with new farmers planting ~20,000 trees in the past few years. To determine the etiology and extent of diseases affecting cacao in Puerto Rico, a survey was performed at eight sites around the island. Pod rot and/or branch dieback were observed at all sites. Most organisms isolated from symptomatic pod and stem samples were identified as Diaporthe spp. (48%) and Lasiodiplodia spp. (25%) based on sequences of the internal transcribed spacer and large subunit regions. Within these genera, Diaporthe tulliensis and Lasiodiplodia theobromae were the most prevalent species and were used in inoculation studies to determine their relative virulence on pods and stems. Phytophthora palmivora served as a positive control due to its well-established pathogenicity in all tissues. On pods, L. theobromae and P. palmivora caused significantly larger lesions (6.1 and 5.9 cm, respectively) than D. tulliensis (2.7 cm) four days post-inoculation. All three species caused disease on stems, with no differences found among species. Although P. palmivora was thought to be the primary pathogen affecting cacao in Puerto Rico, this study identifies L. theobromae and D. tulliensis as the common pathogens on the island. This improved understanding will help scientists and farmers control disease by selecting fungicides effective against both oomycetes and fungi.
Diversity and Pathogenicity of Fusarium Species Associated with Stalk and Crown Rot in Maize in Northern Italy
Authors: Sanna Martina , Martino Ilaria , Guarnaccia Vladimiro , Mezzalama Monica
Published: November 2023

The genus Fusarium includes several agronomically important and toxin-producing species that are distributed worldwide and can cause a wide range of diseases. Crown and stalk rot and grain infections are among the most severe symptoms that Fusarium spp. can cause in maize. Disease development usually occurs during germination, but it may also affect the later phases of plant growth. The purpose of this study was to investigate the diversity and pathogenicity of 41 isolates recovered from symptomatic seedlings collected in Northern Italy and seeds of five different geographical origins in 2019 and 2020. The pathogenicity was tested and confirmed in 23 isolates causing rotting in maize seedlings, with disease indexes from 20% to 90%. A multilocus phylogeny analysis based on four genomic loci (tef1-α, rpb2, calm and tub2) was performed on 23 representative isolates. Representative isolates were identified as species belonging to three species complexes (SC), including Fusarium verticillioides and F. annulatum in the F. fujikuroi SC. Fusarium commune was identified in the F. nisikadoi SC, and three different lineages were found in the Fusarium oxysporum SC. This study reports F. annulatum and two lineages of the Fusarium oxysporum SC as maize pathogens for the first time in Italy.
Hierarchical Machine Learning-Based Growth Prediction Model of Panax ginseng Sprouts in a Hydroponic Environment
Authors: Kim Tae Hyong , Baek Seunghoon , Kwon Ki Hyun , Oh Seung Eel
Published: November 2023

Due to an increase in interest towards functional and health-related foods, Panax ginseng sprout has been in the spotlight since it contains a significant amount of saponins which have anti-cancer, -stress, and -diabetic effects. To increase the amount of production as well as decrease the cultivation period, sprouted ginseng is being studied to ascertain its optimal cultivation environment in hydroponics. Although there are studies on functional components, there is a lack of research on early disease prediction along with productivity improvement. In this study, the ginseng sprouts were cultivated in four different hydroponic conditions: control treatment, hydrogen-mineral treatment, Bioblock treatment, and highly concentrated nitrogen treatment. Physical properties were measured, and environmental data were acquired using sensors. Using three algorithms (artificial neural networks, support vector machines, random forest) for germination and rottenness classification, and leaf number and length of stem prediction models, we propose a hierarchical machine learning model that predicts the growth outcome of ginseng sprouts after a week. Based on the results, a regression model predicts the number of leaves and stem length during the growth process. The results of the classifier models showed an F1-score of germination classification of about 99% every week. The rottenness classification model showed an increase from an average of 83.5% to 98.9%. Predicted leaf numbers for week 1 showed an average nRMSE value of 0.27, which decreased by about 33% by week 3. The results for predicting stem length showed a higher performance compared to the regression model for predicting leaf number. These results showed that the proposed hierarchical machine learning algorithm can predict germination and rottenness in ginseng sprout using physical properties.
Properties and Applications of Self-Healing Polymeric Materials: A Review
Authors: Choi Kiwon , Noh Ahyeon , Kim Jinsil , Hong Pyong Hwa , Ko Min Jae , Hong Sung Woo
Published: November 2023

Self-healing polymeric materials, engineered to autonomously self-restore damages from external stimuli, are at the forefront of sustainable materials research. Their ability to maintain product quality and functionality and prolong product life plays a crucial role in mitigating the environmental burden of plastic waste. Historically, initial research on the development of self-healing materials has focused on extrinsic self-healing systems characterized by the integration of embedded healing agents. These studies have primarily focused on optimizing the release of healing agents and ensuring rapid self-healing capabilities. In contrast, recent advancements have shifted the focus towards intrinsic self-healing systems that utilize their inherent reactivity and interactions within the matrix. These systems offer the advantage of repeated self-healing over the same damaged zone, which is attributed to reversible chemical reactions and supramolecular interactions. This review offers a comprehensive perspective on extrinsic and intrinsic self-healing approaches and elucidates their unique properties and characteristics. Furthermore, various self-healing mechanisms are surveyed, and insights from cutting-edge studies are integrated.
Influence of Chitosan 0.2% in Various Final Cleaning Methods on the Bond Strength of Fiberglass Post to Intrarradicular Dentin
Authors: Camilo Naira Geovana , Gonçalves Alex da Rocha , Flauzino Larissa Pinzan , Bernardes Cristiane Martins Rodrigues , Aranha Andreza Maria Fábio , Lazari-Carvalho Priscilla Cardoso , Carvalho Marco Aurélio de , Oliveira Helder Fernandes de
Published: November 2023

The purpose of this study was to analyze the influence of Chitosan 0.2% in various final cleaning methods on the bond strength of fiberglass post (FP) to intrarradicular dentin. Ninety bovine incisors were sectioned to obtain root remnants measuring 18 mm in length. The roots were divided: G1: EDTA 17%; G2: EDTA 17% + PUI; G3: EDTA 17% + EA; G4: EDTA 17% + XPF; G5: Chitosan 2%; G6: Chitosan 2% + PUI; G7: Chitosan 2% + EA; G8: Chitosan 2% +XPF. After carrying out the cleaning methods, the posts were installed, and the root was cleaved to generate two disks from each root third. Bond strength values (MPa) obtained from the micro push-out test data were assessed by using Kruskal–Wallis and Dwass–Steel–Critchlow–Fligner tests for multiple comparisons (α = 5%). Differences were observed in the cervical third between G1 and G8 (p = 0.038), G4 and G8 (p = 0.003), G6 and G8 (p = 0.049), and Control and G8 (p = 0.019). The final cleaning method influenced the adhesion strength of cemented FP to intrarradicular dentin. Chitosan 0.2% + XPF positively influenced adhesion strength, with the highest values in the cervical third.
Interfacial Water Stability between Modified Phosphogypsum Asphalt Mortar and Aggregate Based on Molecular Dynamics
Authors: Liang Cancan , Li Yilang , Feng Ponan , Li Yuanle
Published: November 2023

The objective of this study is to unravel the modification mechanism of a coupling agent on the water sensitivity of phosphogypsum asphalt mortar. The adhesion process of phosphogypsum asphalt mastic modified with three kinds of coupling agents (KH-550, KH-570, and CS-101) and raw phosphogypsum to the aggregate minerals was simulated based on the molecular dynamics software, Materials Studio 2020, and the water film layer was considered along the simulation. When the three coupling agents were added, the interfacial adhesion work gradually increased with the increase of modified phosphogypsum dosage, and the trends of each model were relatively similar. With the increase of simulation time, the mean square displacement of water molecules of the three interfacial models showed different trends, and the increasing trend rank was unmodified phosphogypsum > KH-550 > KH-570 > CS-101. The diffusion coefficient of the water molecular layer of asphalt mastic modified with CS-101 coupling agent in phosphogypsum shows a significant decrease with the increase of CS-101-modified phosphogypsum (more than 5% mass ratio to asphalt). Compared to raw phosphogypsum asphalt mortar, the addition of coupling agents can significantly limit the diffusion of water molecules and effectively improve the interfacial adhesion work, in which CS-101 coupling agent has the best effect, followed by KH-570 and KH-550.
Progress on a Novel, 3D-Printable Heart Valve Prosthesis
Authors: Schröter Filip , Kühnel Ralf-Uwe , Hartrumpf Martin , Ostovar Roya , Albes Johannes Maximilian
Published: November 2023

(1) Background: Polymeric heart valves are prostheses constructed out of flexible, synthetic materials to combine the advantageous hemodynamics of biological valves with the longevity of mechanical valves. This idea from the early days of heart valve prosthetics has experienced a renaissance in recent years due to advances in polymer science. Here, we present progress on a novel, 3D-printable aortic valve prosthesis, the TIPI valve, removing the foldable metal leaflet restrictor structure in its center. Our aim is to create a competitive alternative to current valve prostheses made from flexible polymers. (2) Methods: Three-dimensional (3D) prototypes were designed and subsequently printed in silicone. Hemodynamic performance was measured with an HKP 2.0 hemodynamic testing device using an aortic valve bioprosthesis (BP), a mechanical prosthesis (MP), and the previously published prototype (TIPI 2.2) as benchmarks. (3) Results: The latest prototype (TIPI 3.4) showed improved performance in terms of regurgitation fraction (TIPI 3.4: 15.2 ± 3.7%, TIPI 2.2: 36.6 ± 5.0%, BP: 8.8 ± 0.3%, MP: 13.2 ± 0.7%), systolic pressure gradient (TIPI 3.4: 11.0 ± 2.7 mmHg, TIPI 2.2: 12.8 ± 2.2 mmHg, BP: 8.2 ± 0.9 mmHg, MP: 10.5 ± 0.6 mmHg), and effective orifice area (EOA, TIPI 3.4: 1.39 cm2, TIPI 2.2: 1.28 cm2, BP: 1.58 cm2, MP: 1.38 cm2), which was equivalent to currently used aortic valve prostheses. (4) Conclusions: Removal of the central restrictor structure alleviated previous concerns about its potential thrombogenicity and significantly increased the area of unobstructed opening. The prototypes showed unidirectional leaflet movement and very promising performance characteristics within our testing setup. The resulting simplicity of the shape compared to other approaches for polymeric heart valves could be suitable not only for 3D printing, but also for fast and easy mass production using molds and modern, highly biocompatible polymers.
Novel Polyurethane-Based Systems Modified with Starch and Phase Change Materials for Bone Tissue Regeneration
Authors: Ordon Klaudia , Szatkowski Piotr , Piekarczyk Wojciech , Pamuła Elżbieta , Pielichowska Kinga
Published: November 2023

Novel polyurethane-based materials have been synthesized by a two-step process using poly(ε–caprolactone) diol (PCL) and 1,3–propanediol/starch (PDO/ST) systems as chain extenders/cross-linkers and 1,6–hexamethylane diisocyante (HDI) as a potential material for bone tissue replacement or bone cements. A poly(ethylene glycol)/starch (PEG/ST) system has been applied as a form-stable phase change material (PCM) to decrease the maximum setting temperature, while hydroxyapatite (HAp) has been used as a bioactive nanofiller. FTIR and SEM-EDX analyses were performed to investigate the structure, surface morphology, and thermal properties of the obtained polyurethanes. FTIR spectroscopy confirmed the chemical structure of the synthesized polyurethanes. SEM-EDX analysis confirmed the incorporation of starch/hydroxyapatite into the polyurethane matrix. Modification with PCMs based on PEG or PEG/starch systems allowed for a decrease in the maximum setting temperature of PUs from 6 to 7.6 °C, depending on the type of PCM used. Thus, the obtained polyurethanes show a good energy storage effect and a good application potential for the synthesis of multifunctional bioactive materials for future use as bone cements.