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24 pages, 1690 KiB  
Article
Neural Network-Based Predictive Control of COVID-19 Transmission Dynamics to Support Institutional Decision-Making
by Cristina-Maria Stăncioi, Iulia Adina Ștefan, Violeta Briciu, Vlad Mureșan, Iulia Clitan, Mihail Abrudean, Mihaela-Ligia Ungureșan, Radu Miron, Ecaterina Stativă, Michaela Nanu, Adriana Topan and Ioana Nanu
Mathematics 2025, 13(15), 2528; https://doi.org/10.3390/math13152528 (registering DOI) - 6 Aug 2025
Abstract
The COVID-19 pandemic was a profoundly influential global occurrence in recent history, impacting daily life, economics, and healthcare systems for an extended period. The abundance of data has been essential in creating models to simulate and forecast the dissemination of infectious illnesses, aiding [...] Read more.
The COVID-19 pandemic was a profoundly influential global occurrence in recent history, impacting daily life, economics, and healthcare systems for an extended period. The abundance of data has been essential in creating models to simulate and forecast the dissemination of infectious illnesses, aiding governments and health organizations in making educated decisions. This research primarily focuses on designing a control technique that incorporates the five most important inputs that impact the spread of COVID-19 on the Romanian territory. Quantitative analysis and data filtering are two crucial aspects to consider when developing a mathematical model. In this study the transfer function principle was used as the most accurate method for modeling the system, based on its superior fit demonstrated in a previous study. For the control strategy, a PI (Proportional-Integral) controller was designed to meet the requirements of the intended behavior. Finally, it is showed that for such complex models, the chosen control strategy, combined with fine tuning, led to very accurate results. Full article
(This article belongs to the Special Issue Control Theory and Applications, 2nd Edition)
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9 pages, 391 KiB  
Article
Meconium and Amniotic Fluid IgG Fc Binding Protein (FcGBP) Concentrations in Neonates Delivered by Cesarean Section and by Vaginal Birth in the Third Trimester of Pregnancy
by Barbara Lisowska-Myjak, Kamil Szczepanik, Ewa Skarżyńska and Artur Jakimiuk
Int. J. Mol. Sci. 2025, 26(15), 7579; https://doi.org/10.3390/ijms26157579 - 5 Aug 2025
Abstract
IgG Fc binding protein (FcGBP) is a mucin-like protein that binds strongly to IgG and IgG–antigen complexes in intestinal mucus. FcGBP presence and its altered expression levels in meconium accumulating in the fetal intestine and amniotic fluid flowing in the intestine may provide [...] Read more.
IgG Fc binding protein (FcGBP) is a mucin-like protein that binds strongly to IgG and IgG–antigen complexes in intestinal mucus. FcGBP presence and its altered expression levels in meconium accumulating in the fetal intestine and amniotic fluid flowing in the intestine may provide new knowledge of the mechanisms responsible for the immune adaptation of the fetus to extrauterine life. FcGBP concentrations were measured by ELISA in the first-pass meconium and amniotic fluid samples collected from 120 healthy neonates delivered by either vaginal birth (n = 35) or cesarean section (n = 85) at 36 to 41 weeks gestation. The meconium FcGBP concentrations (405.78 ± 145.22 ng/g) decreased (r = −0.241, p = 0.007) over the course of 36 to 41 weeks gestation, but there were no significant changes (p > 0.05) in the amniotic fluid FcGBP (135.70 ± 35.83 ng/mL) in the same period. Both meconium and amniotic fluid FcGBP concentrations were higher (p < 0.05) in neonates delivered by cesarean section. Decreases in the meconium FcGBP concentrations correlated (r = −0.37, p = 0.027) with the gestational age in neonates delivered by vaginal birth but not in those delivered by cesarean section (p > 0.05). No association was found between the FcGBP concentrations in meconium and amniotic fluid and the birth weight (p > 0.05). With the development of the mucosal immune system in the fetal intestine over the course of the third trimester of gestation, the meconium FcGBP concentrations decrease. Increased FcGBP concentrations measured in the meconium and amniotic fluid of neonates delivered by cesarean section may possibly indicate altered intestinal mucosal function. Intrauterine growth is not associated with the intestinal mucosal barrier maturation involving FcGBP. Full article
(This article belongs to the Special Issue Female Infertility and Fertility)
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26 pages, 6880 KiB  
Article
IgA Nephropathy in Native Kidneys: Oxford and Banff Classifications Reveal Distinct Profiles and Predict Outcomes in Pediatric and Adult Patients
by Danijel Milivojević, Gorana Nikolić, Björn Tampe, Maja Pecić, Snežana Babac, Dušan Paripović, Gordana Miloševski Lomić, Voin Brković, Marko Baralić, Aleksandar Janković, Petar Đurić, Nataša Stajić, Jovana Putnik, Sanja Radojević Škodrić and Maja Životić
Life 2025, 15(8), 1231; https://doi.org/10.3390/life15081231 - 3 Aug 2025
Viewed by 184
Abstract
IgA nephropathy is the most common primary glomerulonephritis, with pathohistological changes described by the Oxford classification, while the Banff classification is used in transplant pathology. This study included 253 patients with IgA nephropathy in native kidneys, divided into the pediatric (n = [...] Read more.
IgA nephropathy is the most common primary glomerulonephritis, with pathohistological changes described by the Oxford classification, while the Banff classification is used in transplant pathology. This study included 253 patients with IgA nephropathy in native kidneys, divided into the pediatric (n = 105) and adult (n = 148) groups. It aimed to examine clinical, and Oxford and Banff morphological parameters in relation to age, correlations of clinical data with pathohistological parameters, and predictors of the disease outcome. Pediatric patients more frequently presented with macroscopic hematuria, while adults showed higher urea and creatinine levels, and lower eGFR. Examining Oxford classification parameters, chronic glomerular and tubulointerstitial lesions were more common in adults. Banff parameters revealed more frequent chronically active glomerular, inflammatory, chronic tubulointerstitial, and vascular lesions in adults. All inflammatory, chronic tubulointerstitial, and vascular parameters correlated with serum urea levels, eGFR and CKD stage in adults, while less frequent in pediatric patients. Tubulointerstitial Oxford and Banff parameters were strong predictors of CKD and proteinuria progression in children, while such predictors were fewer in adults; segmental glomerulosclerosis predicted hematuria progression in adults. Banff parameters (cg, t, ti, i, i-IFTA, ptc, cv), not in Oxford classification, significantly predict outcomes and are recommended for incorporation into IgA nephropathy reports. Full article
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11 pages, 301 KiB  
Article
Impact of Maternal Overweight and Obesity on Pregnancy Outcomes Following Cesarean Delivery: A Retrospective Cohort Study
by Zlatina Nikolova, Milena Sandeva, Ekaterina Uchikova, Angelina Kirkova-Bogdanova, Daniela Taneva, Marieta Vladimirova and Lyubomira Georgieva
Healthcare 2025, 13(15), 1893; https://doi.org/10.3390/healthcare13151893 - 2 Aug 2025
Viewed by 207
Abstract
Background/Objectives: Maternal overweight and obesity are critical factors increasing the risk of various pregnancy complications. Maternal obesity can lead to fetal macrosomia and a heightened risk of intrauterine death, with long-term implications for the child’s health. This study aimed to analyze the [...] Read more.
Background/Objectives: Maternal overweight and obesity are critical factors increasing the risk of various pregnancy complications. Maternal obesity can lead to fetal macrosomia and a heightened risk of intrauterine death, with long-term implications for the child’s health. This study aimed to analyze the incidence of obesity and its impact on pregnancy outcomes in women who delivered by cesarean section at the University Hospital “St. George”, Plovdiv. Methods: A single-center retrospective cohort study was conducted. The documentary method was used for gathering data. Records were randomly selected. The statistical methods used included mean values, confidence intervals (of mean), frequency, and the Kolmogorov–Smirnov test for normality of distribution. Data comparisons were performed using the Mann–Whitney test. Mean values of numerical variables were compared using the independent samples t-test. Results: In total, 46.36% of women in this study were affected by obesity to varying degrees, and the proportion of women who were overweight at the end of their pregnancy was 37.85%. In the studied cohort, 15.99% of women were affected by hypertensive complications. This significant prevalence of obesity highlights concerns regarding body weight among women of reproductive age. This study emphasized a strong correlation between maternal obesity, particularly severe obesity, and the occurrence of preeclampsia. Conclusions: In this study among women who delivered by cesarean section, a significant proportion of them were affected by overweight and obesity. Data for our country are insufficient, and a more in-depth study of this problem is needed. Future research should explore the long-term impacts of maternal obesity on the health of the mother and the newborn. Full article
(This article belongs to the Special Issue Focus on Maternal, Pregnancy and Child Health)
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25 pages, 906 KiB  
Review
Evolution and Prognostic Variables of Cystic Fibrosis in Children and Young Adults: A Narrative Review
by Mădălina Andreea Donos, Elena Țarcă, Elena Cojocaru, Viorel Țarcă, Lăcrămioara Ionela Butnariu, Valentin Bernic, Paula Popovici, Solange Tamara Roșu, Mihaela Camelia Tîrnovanu, Nicolae Sebastian Ionescu and Laura Mihaela Trandafir
Diagnostics 2025, 15(15), 1940; https://doi.org/10.3390/diagnostics15151940 - 2 Aug 2025
Viewed by 232
Abstract
Introduction: Cystic fibrosis (CF) is a genetic condition affecting several organs and systems, including the pancreas, colon, respiratory system, and reproductive system. The detection of a growing number of CFTR variants and genotypes has contributed to an increase in the CF population which, [...] Read more.
Introduction: Cystic fibrosis (CF) is a genetic condition affecting several organs and systems, including the pancreas, colon, respiratory system, and reproductive system. The detection of a growing number of CFTR variants and genotypes has contributed to an increase in the CF population which, in turn, has had an impact on the overall statistics regarding the prognosis and outcome of the condition. Given the increase in life expectancy, it is critical to better predict outcomes and prognosticate in CF. Thus, each person’s choice to aggressively treat specific disease components can be more appropriate and tailored, further increasing survival. The objective of our narrative review is to summarize the most recent information concerning the value and significance of clinical parameters in predicting outcomes, such as gender, diabetes, liver and pancreatic status, lung function, radiography, bacteriology, and blood and sputum biomarkers of inflammation and disease, and how variations in these parameters affect prognosis from the prenatal stage to maturity. Materials and methods: A methodological search of the available data was performed with regard to prognostic factors in the evolution of CF in children and young adults. We evaluated articles from the PubMed academic search engine using the following search terms: prognostic factors AND children AND cystic fibrosis OR mucoviscidosis. Results: We found that it is crucial to customize CF patients’ care based on their unique clinical and biological parameters, genetics, and related comorbidities. Conclusions: The predictive significance of more dynamic clinical condition markers provides more realistic future objectives to center treatment and targets for each patient. Over the past ten years, improvements in care, diagnostics, and treatment have impacted the prognosis for CF. Although genotyping offers a way to categorize CF to direct research and treatment, it is crucial to understand that a variety of other factors, such as epigenetics, genetic modifiers, environmental factors, and socioeconomic status, can affect CF outcomes. The long-term management of this complicated multisystem condition has been made easier for patients, their families, and physicians by earlier and more accurate identification techniques, evidence-based research, and centralized expert multidisciplinary care. Full article
(This article belongs to the Special Issue Advances in the Diagnosis of Inherited/Genetic Diseases)
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15 pages, 524 KiB  
Systematic Review
Association Between Maternal Diet and Frequency of Micronuclei in Mothers and Newborns: A Systematic Review
by Anny Cristine de Araújo, Priscila Kelly da Silva Bezerra do Nascimento, Marília Cristina Santos de Medeiros, Raul Hernandes Bortolin, Ricardo Ney Cobucci and Adriana Augusto de Rezende
Nutrients 2025, 17(15), 2535; https://doi.org/10.3390/nu17152535 - 1 Aug 2025
Viewed by 183
Abstract
Background/Objectives: The effect of diet on maternal and infant genetic levels has been reported in the literature. Diet-associated DNA damage, such as the presence of micronuclei (MN), may be related to an increased risk of developing chronic diseases such as cancer. There is [...] Read more.
Background/Objectives: The effect of diet on maternal and infant genetic levels has been reported in the literature. Diet-associated DNA damage, such as the presence of micronuclei (MN), may be related to an increased risk of developing chronic diseases such as cancer. There is particular concern regarding this damage during pregnancy, as it may affect the newborn (NB). Thus, this review aims to summarize the primary evidence of the impact of diet on the frequency of MN in the mother–infant population. Methods: Five databases (PubMed, Embase, Web of Science, Scopus, and ScienceDirect) were used to search for observational studies. Google Scholar and manual searching were required to perform the “gray literature” search. Results: The search strategy retrieved 1418 records. Of these, 13 were read in full and 5 were included in the review. Most studies were of the cohort type (n = 4) and were carried out in the European region. A total of 875 pregnant women and 238 newborns were evaluated. Despite insufficient evidence to confirm that diet changes the frequency of MN, the included studies found possible effects from the consumption of fried red meat and processed meats and the adequate consumption of vegetables and polyunsaturated fats. Conclusions: Future research is needed in order to understand the effects of diet on genetic stability and to obtain evidence to help plan public policies on food and nutrition or reinforce protective dietary patterns for this and future generations. Full article
(This article belongs to the Section Nutrition in Women)
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20 pages, 1376 KiB  
Article
Comienzo Saludable Puerto Rico: A Community-Based Network of Care to Improve Maternal, Newborn, and Child Health Outcomes
by Edna Acosta-Pérez, Cristina Díaz, Atisha Gómez-Reyes, Samaris Vega, Carlamarie Noboa Ramos, Rosario Justinianes-Pérez, Glamarie Ferran, Jessica Carnivali-García, Fabiola J. Grau, Lili M. Sardiñas, Maribel Campos and Marizaida Sánchez Cesareo
Int. J. Environ. Res. Public Health 2025, 22(8), 1204; https://doi.org/10.3390/ijerph22081204 - 31 Jul 2025
Viewed by 178
Abstract
Background: Maternal and newborn health disparities remain a challenge in Puerto Rico, especially in underserved communities. Comienzo Saludable Puerto Rico, sponsored by the U.S. Department of Health and Human Services’ Healthy Start Initiative (HRSA), addresses these gaps through an integrated Networks of Care [...] Read more.
Background: Maternal and newborn health disparities remain a challenge in Puerto Rico, especially in underserved communities. Comienzo Saludable Puerto Rico, sponsored by the U.S. Department of Health and Human Services’ Healthy Start Initiative (HRSA), addresses these gaps through an integrated Networks of Care model known as Cuidado Compartido. Comienzo Saludable Puerto Rico is a maternal, paternal, and child health program aimed at improving the health and well-being of pregnant women, mothers, fathers, newborns, and children in Puerto Rico, particularly those from disadvantaged communities. Methods: This paper presents the Comienzo Saludable Puerto Rico program’s Cuidado Compartido model to integrate a network of healthcare providers and services across hospitals, community organizations, and families. This model aims to improve maternal and newborn/child health outcomes by focusing on the importance of integrated, hospital-community-based care networks. Results: Participants experienced significant improvements in key birth outcomes: low birth weight prevalence declined by 27.2% compared to the community baseline, premature birth rates decreased by 30.9%, and infant mortality dropped by 75%, reaching 0% by 2021 and remaining there through 2023. These results were complemented by increases in maternal mental health screening, paternal involvement, and breastfeeding practices. Conclusions: The Cuidado Compartido model demonstrates a scalable, culturally responsive strategy to improve maternal, newborn, and child health outcomes. It offers critical insights for implementation in other high-need contexts. Full article
(This article belongs to the Special Issue Community Interventions in Health Disparities)
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18 pages, 706 KiB  
Review
Hyaluronic Acid in Female Reproductive Health: Tailoring Molecular Weight to Clinical Needs in Obstetric and Gynecological Fields
by Giuseppina Porcaro, Ilenia Mappa, Francesco Leonforte, Giorgio Maria Baldini, Maria Francesca Guarneri, Marco La Verde, Felice Sorrentino and Antonio Simone Laganà
Pharmaceutics 2025, 17(8), 991; https://doi.org/10.3390/pharmaceutics17080991 (registering DOI) - 30 Jul 2025
Viewed by 269
Abstract
Hyaluronic acid (HA) is a ubiquitous glycosaminoglycan with distinct biological functions, dependent on its molecular weight. High-molecular-weight HA (HMWHA) primarily exhibits structural and anti-inflammatory roles, whereas low-(LMWHA) and very low-molecular-weight HAs (vLMWHA) actively participate in tissue regeneration and angiogenesis. This review highlights the [...] Read more.
Hyaluronic acid (HA) is a ubiquitous glycosaminoglycan with distinct biological functions, dependent on its molecular weight. High-molecular-weight HA (HMWHA) primarily exhibits structural and anti-inflammatory roles, whereas low-(LMWHA) and very low-molecular-weight HAs (vLMWHA) actively participate in tissue regeneration and angiogenesis. This review highlights the pivotal roles of HA across the female reproductive lifespan, emphasizing how molecular weight dictates its therapeutic potential. In gynecology, LMWHA effectively alleviates symptoms of genitourinary syndrome of menopause, restores vaginal architecture, and mitigates complications following pelvic radiotherapy, improving both tissue integrity and patient quality of life. vLMWHA shows promise in enhancing viral clearance and lesion regression in human papillomavirus (HPV) infections. In obstetrics, HMWHA plays crucial roles in implantation, immunotolerance, and embryogenesis and maintains cervical barrier integrity to prevent ascending infections and preterm birth. Moreover, emerging clinical evidence supports oral HMWHA supplementation for reducing pregnancy complications, such as threatened miscarriage, subchorionic hematomas, and preterm delivery. This review underscores the necessity of considering HA’s molecular weight to optimize interventions in gynecological and obstetric care, offering tailored strategies to support women’s health throughout their lives. Full article
(This article belongs to the Special Issue Hyaluronic Acid for Medical Applications)
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17 pages, 386 KiB  
Article
Growth Hormone Therapy in Recurrent Implantation Failure: Stratification by FSH Receptor Polymorphism (Asn680Ser) Reveals Genotype-Specific Benefits
by Mihai Surcel, Georgiana Nemeti, Iulian Gabriel Goidescu, Romeo Micu, Cristina Zlatescu-Marton, Ariana Anamaria Cordos, Gabriela Caracostea, Ioana Cristina Rotar, Daniel Muresan and Dan Boitor-Borza
Int. J. Mol. Sci. 2025, 26(15), 7367; https://doi.org/10.3390/ijms26157367 - 30 Jul 2025
Viewed by 178
Abstract
Recurrent implantation failure (RIF) remains a challenging clinical problem. Growth hormone (GH) co-treatment has been explored as an adjunct in poor responders and RIF patients, with inconsistent evidence of benefit. This prospective cohort study assessed the impact of GH supplementation in 91 RIF [...] Read more.
Recurrent implantation failure (RIF) remains a challenging clinical problem. Growth hormone (GH) co-treatment has been explored as an adjunct in poor responders and RIF patients, with inconsistent evidence of benefit. This prospective cohort study assessed the impact of GH supplementation in 91 RIF patients undergoing in vitro fertilization, stratified by FSHR (follicular stimulating hormone receptor) genotype Asn680Ser with or without GH supplementation. Patients were stratified by FSHR genotype into homozygous Ser/Ser versus Ser/Asn or Asn/Asn groups. Overall, GH co-treatment conferred modest benefits in the unselected RIF cohort, limited to a higher cumulative live birth rate compared to controls and elevated leukemia inhibitory factor (LIF) levels (p < 0.05 both). When stratified by FSHR genotype, the Ser/Ser subgroup exhibited markedly better outcomes with GH. These patients showed a higher (0.5 vs. 0.33, p = 0.003), produced more embryos (2.88 vs. 1.53, p = 0.02), and had a markedly improved cumulative live birth rate—50% with GH versus 13% without—highlighting a clinically meaningful benefit of GH in the Ser/Ser subgroup. No significant benefit was observed in Asn allele carriers. These findings suggest that FSHR genotyping may help optimize treatment selection in RIF patients by identifying those most likely to benefit from GH supplementation. Full article
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23 pages, 2248 KiB  
Article
Autonomic and Neuroendocrine Reactivity to VR Game Exposure in Children and Adolescents with Obesity: A Factor Analytic Approach to Physiological Reactivity and Eating Behavior
by Cristiana Amalia Onita, Daniela-Viorelia Matei, Laura-Mihaela Trandafir, Diana Petrescu-Miron, Calin Corciova, Robert Fuior, Lorena-Mihaela Manole, Bogdan-Mircea Mihai, Cristina-Gena Dascalu, Monica Tarcea, Stéphane Bouchard and Veronica Mocanu
Nutrients 2025, 17(15), 2492; https://doi.org/10.3390/nu17152492 - 30 Jul 2025
Viewed by 285
Abstract
Background/Objectives: The aim was to identify patterns of autonomic and neuroendocrine reactivity to an immersive virtual reality (VR) social-emotional stressor and explore their associations with perceived stress and eating behavior. Methods: This one-group pretest–posttest study included 30 children and adolescents with [...] Read more.
Background/Objectives: The aim was to identify patterns of autonomic and neuroendocrine reactivity to an immersive virtual reality (VR) social-emotional stressor and explore their associations with perceived stress and eating behavior. Methods: This one-group pretest–posttest study included 30 children and adolescents with obesity (15 boys and 15 girls), aged 8 to 17 years. The VR protocol consisted of two consecutive phases: a 5 min relaxation phase using the Forest application and a 5 min stimulation phase using a cognitively engaging VR game designed to elicit social-emotional stress. Physiological responses were measured using heart rate variability (HRV) indices and salivary stress biomarkers, including cortisol and alpha amylase. Subjective stress and eating responses were assessed via visual analogue scales (VAS) administered immediately post-exposure. The Three-Factor Eating Questionnaire (TFEQ-R21C) was used to evaluate cognitive restraint (CR), uncontrolled eating (UE), and emotional eating (EE). Results: The cortisol reactivity was blunted and may reflect both the attenuated HPA axis responsiveness characteristic of pediatric obesity and the moderate psychological challenge of the VR stressor used in this study. Two distinct autonomic response patterns were identified via exploratory factor analysis: (1) parasympathetic reactivity, associated with increased RMSSD and SDNN and decreased LF/HF, and (2) sympathetic activation, associated with increased heart rate and alpha-amylase levels and reduced RR intervals. Parasympathetic reactivity was correlated with lower perceived stress and anxiety, but also paradoxically with higher uncontrolled eating (UE). In contrast, sympathetic activation was associated with greater cognitive restraint (CR) and higher anxiety ratings. Conclusions: This study demonstrates that immersive VR game exposure elicits measurable autonomic and subjective stress responses in children and adolescents with obesity, and that individual differences in physiological reactivity are relevantly associated with eating behavior traits. The findings suggest that parasympathetic and sympathetic profiles may represent distinct behavioral patterns with implications for targeted intervention. Full article
(This article belongs to the Special Issue A Path Towards Personalized Smart Nutrition)
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15 pages, 443 KiB  
Article
Prematurity and Low Birth Weight Among Food-Secure and Food-Insecure Households: A Comparative Study in Surabaya, Indonesia
by Arie Dwi Alristina, Nour Mahrouseh, Anggi Septia Irawan, Rizky Dzariyani Laili, Alexandra Vivien Zimonyi-Bakó and Helga Judit Feith
Nutrients 2025, 17(15), 2479; https://doi.org/10.3390/nu17152479 - 29 Jul 2025
Viewed by 199
Abstract
Background: Prematurity and low birth weight (LBW) drive infant morbidity and mortality, requiring nutritional interventions, especially in food-insecure settings. In Indonesia, regional disparities in food security hinder adequate nutrition for premature and LBW infants, exacerbating health challenges. The aim of study is [...] Read more.
Background: Prematurity and low birth weight (LBW) drive infant morbidity and mortality, requiring nutritional interventions, especially in food-insecure settings. In Indonesia, regional disparities in food security hinder adequate nutrition for premature and LBW infants, exacerbating health challenges. The aim of study is to investigate and determine factors associated with prematurity and LBW in children from food-insecure and food-secure households. Methods: This research employed a cross-sectional study with 657 mothers of children aged 36–59 months, conducted using random sampling. Data was collected via standardized questionnaires and analyzed using Chi-square tests and logistic regression. Results: The adjusted model showed that children of food-insecure households had a higher risk of LBW (AOR = 0.54; 95% CI: 0.29–0.99; p < 0.05). LBWs were found to significantly less occur in food-insecure households. Low maternal education was associated with an increased risk of preterm birth (AOR = 3.23; 95% CI:1.78–5.84; p < 0.001). Furthermore, prematurity correlated with house ownership (p < 0.01), indicating the household’s wealth condition. Maternal education and house ownership were linked to prematurity, indicating the risk to child health outcomes. In summary, maternal education, employment status, and household income were linked to food insecurity, indicating the risk to child health outcomes. Conclusion: Strategies to improve child health outcomes are essential, including enhancing maternal nutrition knowledge to improve child feeding practices, promoting gender equality in career development, and reducing food insecurity in households. Full article
(This article belongs to the Section Pediatric Nutrition)
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18 pages, 670 KiB  
Article
Genetic Heterogeneity Correlated with Phenotypic Variability in 48 Patients with Cystic Fibrosis
by Mădălina Andreea Donos, Lăcrămioara Ionela Butnariu, Dana Teodora Anton Păduraru, Alina Mariela Murgu, Cristina Rusu, Monica Cristina Pânzaru, Roxana Popescu, Elena Țarcă, Elena Cojocaru, Gabriela Ghiga and Laura Mihaela Trandafir
J. Clin. Med. 2025, 14(15), 5362; https://doi.org/10.3390/jcm14155362 - 29 Jul 2025
Viewed by 220
Abstract
Background/Objectives: Cystic fibrosis (CF) is a rare autosomal recessive genetic disease that has a progressive and multisystemic course. The spectrum and frequency of mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) vary both in European countries and in [...] Read more.
Background/Objectives: Cystic fibrosis (CF) is a rare autosomal recessive genetic disease that has a progressive and multisystemic course. The spectrum and frequency of mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) vary both in European countries and in other geographical regions. The aim of our retrospective study was to present the genetic variants identified in a group of 48 CF patients from the Moldova region (Romania), as well as to establish genotype–phenotype correlations. Methods: Genetic testing was initially performed for 38 CFTR mutations, and in heterozygous patients or those in whom no mutation was detected, CFTR gene sequencing (NGS) was performed. Results: The compound heterozygous genotype was identified in 26 (54.16%) of the patients (with one of the alleles being F508del), while 22 (45.83%) patients had the homozygous F508del genotype. The F508del variant was the most frequent (69.79%), followed by G542X (6.25%, 6/96). Several new variants were also identified that had not been reported in other studies from Romania (R1158X, K598*, R347H, c.2589_2599del, R496H, and CFTRdele2). Phenotypic manifestations in patients with CFTR class I, II, III and VII variants (homozygous and compound heterozygous) were more severe compared to those in patients with CFTR class IV, V and VI mutations, with the data obtained being consistent with those in the literature. Respiratory tract involvement was present in 77.08% of the patients, being more frequent in patients with the compound heterozygous genotype compared to the homozygous F508del genotype. Most patients had exocrine pancreatic insufficiency (EPI) (85.41%). Gastrointestinal manifestations included hepatocytolysis (66.66%) and biliary cirrhosis (0.41%). Meconium ileus was detected in 18.75% of patients, all with a compound heterozygous genotype. Conclusions: We compared the results obtained with data from the literature and correlated the detected CFTR variant (genotype) with the phenotypic manifestations, highlighting certain particularities present in some patients. Genetic testing allows for early diagnosis and adapted management, including personalized treatment for each patient. Identification of novel unclassified CFTR variants still remains a challenge for clinicians. NGS-based screening of heterozygous healthy carriers is important for both genetic counseling and prenatal diagnosis. Full article
(This article belongs to the Special Issue Cystic Fibrosis: Clinical Manifestations and Treatment)
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24 pages, 528 KiB  
Review
Therapeutic and Prognostic Relevance of Cancer Stem Cell Populations in Endometrial Cancer: A Narrative Review
by Ioana Cristina Rotar, Elena Bernad, Liviu Moraru, Viviana Ivan, Adrian Apostol, Sandor Ianos Bernad, Daniel Muresan and Melinda-Ildiko Mitranovici
Diagnostics 2025, 15(15), 1872; https://doi.org/10.3390/diagnostics15151872 - 25 Jul 2025
Viewed by 243
Abstract
The biggest challenge in cancer therapy is tumor resistance to the classical approach. Thus, research interest has shifted toward the cancer stem cell population (CSC). CSCs are a small subpopulation of cancer cells within tumors with self-renewal, differentiation, and metastasis/malignant potential. They are [...] Read more.
The biggest challenge in cancer therapy is tumor resistance to the classical approach. Thus, research interest has shifted toward the cancer stem cell population (CSC). CSCs are a small subpopulation of cancer cells within tumors with self-renewal, differentiation, and metastasis/malignant potential. They are involved in tumor initiation and development, metastasis, and recurrence. Method. A narrative review of significant scientific publications related to the topic and its applicability in endometrial cancer (EC) was performed with the aim of identifying current knowledge about the identification of CSC populations in endometrial cancer, their biological significance, prognostic impact, and therapeutic targeting. Results: Therapy against the tumor population alone has no or negligible effect on CSCs. CSCs, due to their stemness and therapeutic resistance, cause tumor relapse. They target CSCs that may lead to noticeable persistent tumoral regression. Also, they can be used as a predictive marker for poor prognosis. Reverse transcription–polymerase chain reaction (RT-PCR) demonstrated that the cultured cells strongly expressed stemness-related genes, such as SOX-2 (sex-determining region Y-box 2), NANOG (Nanog homeobox), and Oct 4 (octamer-binding protein 4). The expression of surface markers CD133+ and CD44+ was found on CSC as stemness markers. Along with surface markers, transcription factors such as NF-kB, HIF-1a, and b-catenin were also considered therapeutic targets. Hypoxia is another vital feature of the tumor environment and aids in the maintenance of the stemness of CSCs. This involves the hypoxic activation of the WNT/b-catenin pathway, which promotes tumor survival and metastasis. Specific antibodies have been investigated against CSC markers; for example, anti-CD44 antibodies have been demonstrated to have potential against different CSCs in preclinical investigations. Anti-CD-133 antibodies have also been developed. Targeting the CSC microenvironment is a possible drug target for CSCs. Focusing on stemness-related genes, such as the transcription pluripotency factors SOX2, NANOG, and OCT4, is another therapeutic option. Conclusions: Stemness surface and gene markers can be potential prognostic biomarkers and management approaches for cases with drug-resistant endometrial cancers. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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18 pages, 4263 KiB  
Article
Clinical Characteristics, Diagnosis, and Management of Primary Malignant Lung Tumors in Children: A Single-Center Analysis
by Mihail Basa, Nemanja Mitrovic, Dragana Aleksic, Gordana Samardzija, Mila Stajevic, Ivan Dizdarevic, Marija Dencic Fekete, Tijana Grba and Aleksandar Sovtic
Biomedicines 2025, 13(8), 1824; https://doi.org/10.3390/biomedicines13081824 - 25 Jul 2025
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Abstract
Background/Objectives: Primary malignant lung tumors in children are rare and diagnostically challenging. This study presents a single-center experience in the diagnosis and treatment of these tumors, emphasizing the role of histopathological and genetic profiling in informing individualized therapeutic strategies. Methods: We [...] Read more.
Background/Objectives: Primary malignant lung tumors in children are rare and diagnostically challenging. This study presents a single-center experience in the diagnosis and treatment of these tumors, emphasizing the role of histopathological and genetic profiling in informing individualized therapeutic strategies. Methods: We retrospectively reviewed records of seven pediatric patients (ages 2–18) treated from 2015 to 2025. Diagnostics included laboratory tests, chest CT, bronchoscopy, and histopathological/immunohistochemical analysis. Treatment primarily involved surgical resection, complemented by chemo-, radio-, or targeted therapies when indicated. Results: Inflammatory myofibroblastic tumor (IMT) represented the most commonly diagnosed entity (3/7 cases). The tumors presented with nonspecific symptoms, most frequently dry cough. Tumor type distribution was age-dependent, with aggressive forms such as pleuropulmonary blastoma predominantly affecting younger children, whereas IMT and carcinoid tumors were more common in older patients. Surgical resection remained the mainstay of treatment in the majority of cases. Bronchoscopy served as a valuable adjunct in the initial management of tumors exhibiting intraluminal growth, allowing for direct visualization, tissue sampling, and partial debulking to alleviate airway obstruction. In patients with an initially unresectable IMT harboring specific gene fusion rearrangement (e.g., TFG::ROS1), neoadjuvant targeted therapy with crizotinib enabled adequate tumor shrinkage to allow for subsequent surgical resection. Two patients in the study cohort died as a result of disease progression. Conclusions: A multidisciplinary diagnostic approach—integrating radiologic, bronchoscopic, histopathological, and genetic evaluations—ensures high diagnostic accuracy. While conventional treatments remain curative in many cases, targeted therapies directed at specific molecular alterations may offer essential therapeutic options for selected patients. Full article
(This article belongs to the Section Cancer Biology and Oncology)
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12 pages, 1475 KiB  
Article
The Prevalence and Clinical Significance of Toe Walking in Autism Spectrum Disorder: A Cross-Sectional Study in an Italian Pediatric Sample
by Carola Costanza, Beatrice Gallai, Michele Sorrentino, Martina Gnazzo, Giulia Pisanò, Lucia Parisi, Eva Germanò, Agata Maltese, Maria Esposito, Michele Roccella and Marco Carotenuto
Medicina 2025, 61(8), 1346; https://doi.org/10.3390/medicina61081346 - 25 Jul 2025
Viewed by 366
Abstract
Background and Objectives: Toe walking (TW) is frequently observed in children with Autism Spectrum Disorder (ASD), yet its clinical significance and association with comorbid conditions remain poorly understood. This study aimed to examine the prevalence of TW in a large Italian cohort [...] Read more.
Background and Objectives: Toe walking (TW) is frequently observed in children with Autism Spectrum Disorder (ASD), yet its clinical significance and association with comorbid conditions remain poorly understood. This study aimed to examine the prevalence of TW in a large Italian cohort of children with ASD and to explore its association with ASD severity, sleep disturbances, feeding behaviors, and gastrointestinal symptoms. Materials and Methods: A total of 289 children with ASD and 289 typically developing controls (TDC), matched for age and sex, were evaluated in a multicentric observational study. TW was assessed during neurodevelopmental evaluations. Sleep quality was assessed using the Sleep Disturbance Scale for Children (SDSC), feeding behaviors via the Brief Autism Mealtime Behavior Inventory (BAMBI), and gastrointestinal symptoms through clinical reporting. Statistical analyses included Chi-square tests, Mann–Whitney U tests, Spearman correlations, and logistic regressions. Results: TW was significantly more prevalent in the ASD group (27.3%) than in TDC (5.5%, p < 0.0001). Within the ASD group, TW occurred in 50.5% of children with Level 3 severity but was absent in Levels 1 and 2 (p < 0.0001). Males exhibited TW more frequently than females. Children with TW had higher SDSC scores (ρ = 0.33, p < 0.0001), though no subscale independently predicted TW. Constipation was reported in 100% of children with Level 3 ASD and was strongly correlated with SDSC total scores (ρ = 0.58, p < 0.0001). The Disorders of Arousal (DA) subscale emerged as an independent predictor of constipation (β = 0.184, p = 0.019). Conclusions: TW in ASD appears to be a marker of greater neurodevelopmental severity and is associated with sleep disturbances and gastrointestinal dysfunction. These findings support the hypothesis that TW may reflect broader dysfunctions involving the gut–brain axis, sensory processing, and motor control. The routine clinical assessment of TW should include the evaluation of sleep and somatic symptoms to better understand the multisystemic nature of ASD phenotypes. Full article
(This article belongs to the Section Pediatrics)
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