Miracle-dz/UniFAR-FTUs huggingface dataset:
The Emerging Role of Sfrp5 and Wnt5a in the Pathogenesis of Obesity: Implications for a Healthy Diet and Lifestyle

In recent decades, the prevalence of obesity has risen dramatically worldwide among all age groups. Obesity is characterized by excess fat accumulation and chronic low-grade inflammation. The adipose tissue functions as a metabolically active endocrine organ secreting adipokines. A novel duo of adipokines, the anti-inflammatory secreted frizzled-related protein 5 (Sfrp5) and the proinflammatory wingless type mouse mammary tumor virus (MMTV) integration site family member 5A (Wnt5a), signal via the non-canonical Wnt pathway. Recent evidence suggests that Sfpr5 and Wnt5a play a key role in the pathogenesis of obesity and its metabolic complications. This review summarizes the current knowledge on the novel regulatory system of anti-inflammatory Sfrp5 and pro-inflammatory Wnt5a, and their relation to obesity and obesity-related complications. Future studies are required to investigate the potential role of Sfrp5 and Wnt5a as biomarkers for monitoring the response to lifestyle interventions and for predicting the development of cardiometabolic risk factors. These adipokines may also serve as novel therapeutic targets for obesity-related disorders.
A Qualitative Study of Motivators, Strategies, Barriers, and Learning Needs Related to Healthy Cooking during Pregnancy

Nutrition during pregnancy has lifelong impacts on the health of mother and child. However, this life stage presents unique challenges to healthy cooking and eating. Cooking interventions show promising results, but often lack theoretical basis and rigorous evaluation. The objective of this formative, qualitative study was to explore motivators, strategies, and barriers related to healthy cooking during pregnancy. Pregnant individuals’ preferences for a cooking education program were also explored. We conducted five focus groups with pregnant individuals (n = 20) in Southeast Michigan in 2019. Focus groups were audio-recorded and transcribed verbatim, then double coded by two members of the research team. Mean gestational age was 18.3 ± 9.6 weeks. Common motivators included feeding other children, avoiding pregnancy complications, promoting fetal growth, and avoiding foodborne illness. Challenges included pregnancy symptoms, navigating nutrition recommendations, mental energy of meal planning, family preferences, and time constraints. Strategies employed were meal planning and including a variety of foods. Participants identified organizational strategies, recipes, nutrition information, and peer support as important components of a cooking intervention during pregnancy. This study characterized multiple challenges to healthy home cooking during pregnancy, providing novel insight to inform the development of cooking skills education programs during this important life stage.
Preliminary Investigations into the Use of Amylases and Lactic Acid Bacteria to Obtain Fermented Vegetable Products

Legumes are valuable sources of proteins and other functional components. However, the high starch content can be an impediment in developing new vegan food formulations. Enzyme-assisted hydrolysis was used to hydrolyze the starch from chickpea and broad bean vegetable milk to further develop vegetable lactic acid-fermented products. The antioxidant activity of legumes was tested, and it was observed that the overall antioxidant activity (DPPH radical scavenging ability) significantly increased after enzyme-assisted hydrolysis while total phenols content decreased. The obtained vegetable milk was then fermented using exopolysaccharides-producing lactic acid bacteria. A significant decolorization was observed after fermentation in the case of broad bean-based products. Rheological behavior of the fermented products was determined using small amplitude oscillatory measurements and the three-interval thixotropy test. Results showed higher complex viscosity values for broad bean-based products, which displayed a weak gel-like structure. The starter cultures used for vegetable milk samples fermentation influenced the resistance to flow.
Tumor Characteristic Variations between Symptomatic and Asymptomatic Endometrial Cancer

Endometrial cancer is the most common gynecologic malignancy in Europe and usually diagnosed in its initial stage owing to early symptoms of abnormal bleeding. There is no population screening for this disease, although it can sometimes be accidentally diagnosed in asymptomatic patients. Our study aims to determine differences in clinical and tumor characteristics between an asymptomatic and symptomatic group of patients. This unicentric prospective observational study took place in University Hospital Brno between January 2016 and December 2019. A total of 264 patients met inclusion criteria (26% asymptomatic, 74% with reported symptoms). We did not find a statistically significant difference in clinical characteristics (menopausal status, parity, age, BMI, and serum level of CA 125) between groups. According to ultrasound examination, bleeding tumors were larger (19.5 vs. 12.7 mm, p ≤ 0.001). Definitive histology results indicated more frequent lymphovascular space invasion (p < 0.001), along with deep myometrial (p = 0.001) and cervical (p = 0.002) invasion. There was no difference in advanced stages of the tumor. We did not substantiate statistically significant difference in immunohistochemical profile (estrogen and progesterone receptors, L1 cell adhesion molecule, tumor protein p53), which is relevant for tumor recurrence risk and survival capacity. Our conclusions affirmed that bleeding occurs more often among patients with local tumor invasion into the myometrium and cervical stroma. Final International Federation of Gynecology and Obstetrics (FIGO) stage, histology, and immunohistochemical characteristics do not significantly affect symptom appearance.
Human Milk Endocannabinoid Levels as a Function of Obesity and Diurnal Rhythm

The endocannabinoid system is involved in the regulation of a variety of physiological and cognitive processes. While the endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide (N-arachidonoylethanolamine, AEA) have been found in breast milk, their role(s) have yet to be determined. This study determined the normal concentration ranges of endocannabinoids (2-AG and AEA) in breast milk and the influences, if any, of obesity and diurnal rhythms on their levels. Milk samples were collected from 36 breastfeeding mothers at 4–8 weeks postpartum at each feed over a 24-h period, and further stratified into three groups based on body mass index (BMI). The samples were analyzed using liquid chromatography mass spectrometry. AEA was below the limit of detection and 2-AG levels averaged 59.3 ± 18.3 ng/mL (± SD) in women with normal BMI. Wide-ranging 2-AG concentrations in the overweight (65.5 ± 41.9 ng/mL) /obese (66.1 ± 40.6 ng/mL) groups suggest BMI may be a contributing factor influencing its levels. Following a diurnal pattern, there was a significantly higher 2-AG concentration observed during the day, as compared to night time samples. In conclusion, our study clearly suggests that appropriate milk collection and storage conditions are critical. Further, body weight and diurnal rhythm appear to influence levels of 2-AG. Based on these results, future studies are underway to determine what specific roles endocannabinoids may play in human milk and how elevated levels of 2-AG may modulate infant appetite and health.
Current and Future Pathotyping Platforms for Plasmodiophora brassicae in Canada

Clubroot, caused by Plasmodiophora brassicae, is one of the most detrimental threats to crucifers worldwide and has emerged as an important disease of canola (Brassica napus) in Canada. At present, pathotypes are distinguished phenotypically by their virulence patterns on host differential sets, including the systems of Williams, Somé et al., the European Clubroot Differential set, and most recently the Canadian Clubroot Differential set and the Sinitic Clubroot Differential set. Although these are frequently used because of their simplicity of application, they are time-consuming, labor-intensive, and can lack sensitivity. Early, preventative pathotype detection is imperative to maximize productivity and promote sustainable crop production. The decreased turnaround time and increased sensitivity and specificity of genotypic pathotyping will be valuable for the development of integrated clubroot management plans, and interest in molecular techniques to complement phenotypic methods is increasing. This review provides a synopsis of current and future molecular pathotyping platforms for P. brassicae and aims to provide information on techniques that may be most suitable for the development of rapid, reliable, and cost-effective pathotyping assays.
Liqui-Mass Technology as a Novel Tool to Produce Sustained Release Liqui-Tablet Made from Liqui-Pellets

The Liqui-Mass technology (also known as Liqui-Pellet technology) has shown promising results in terms of enhancing the drug release rate of water insoluble drugs in a simplistic approach. However, there is no current study on sustained-release formulation using the Liqui-Mass technology. In this study, an attempt was made to produce a sustained-release Liqui-Tablet for the first time using a matrix-based approach. The non-volatile co-solvent used in the investigation included Tween 80, Tween 20 and Kolliphor EL. The production of sustained-release propranolol hydrochloride Liqui-Tablet was successful, and data from the saturation solubility test and dissolution test did not show much difference among the mentioned non-volatile co-solvent. The best Liqui-Tablet formulation took 24 h for drug release to reach at around 100%. There seemed to be a synergistic retarding drug release effect when a non-volatile co-solvent and Eudragit RS PO were used together. The increase of Eudragit RS PO concentration increased the retardant effect. Kinetic drug release analysis suggests that the best formulation followed the Higuchi model. The flowability of pre-compressed Liqui-Tablet pellets had no issues and its size distribution was narrow. Liqui-Tablet was generally robust and most formulations passed the friability test. The study revealed that Liqui-Mass technology can be employed to sustain drug release.
Clinical Usefulness of Ultrasound-Guided Fine Needle Aspiration and Core Needle Biopsy for Patients with Axillary Lymphadenopathy

Background and Objectives: It is necessary to properly diagnose and manage axillary lymphadenopathy caused by a variety of diseases. This study aimed to evaluate the utility of ultrasound (US)-guided sampling in patients with axillary lymphadenopathy. Materials and Methods: Patients with axillary lymphadenopathy (excluding patients with newly diagnosed breast cancer) who underwent US-guided fine needle aspiration (FNA) or core needle biopsy (CNB) at a single center between February 2016 and September 2020 were retrospectively examined. The association between US imaging findings and malignancy was investigated and the diagnostic performance of US-guided sampling was assessed. Results: Fifty-five patients (including eight males) were included in the study; of these, 34 patients (61.8%) were finally diagnosed with a malignant lymph node lesion. Twenty-two patients (40.0%) had undergone FNA and 33 (60.0%) had undergone CNB. Larger short and long axis diameters, thicker lymph node cortex, and the absence of fatty hilum on the US were significantly associated with malignancy (p < 0.05). The diagnostic performance of FNA, CNB, and FNA + CNB was excellent (sensitivity, specificity, and accuracy of 0.909, 0.900, and 0.917 for FNA, 0.958, 1.000, and 0.970 for CNB, and 0.941, 0.952, and 0.945 for FNA + CNB, respectively). Conclusions: US-guided FNA and CNB play an important role in the diagnosis and management of patients with axillary lymphadenopathy.
Merging the Multi-Target Effects of Kleeb Bua Daeng, a Thai Traditional Herbal Formula in Unpredictable Chronic Mild Stress-Induced Depression

Major depressive disorder (MDD) is a common and debilitating psychiatric disease characterized by persistent low mood, lack of energy, hypoactivity, anhedonia, decreased libido, and impaired cognitive and social functions. However, the multifactorial etiology of MDD remains largely unknown due the complex interaction between genetics and environment involved. Kleeb Bua Daeng (KBD) is a Thai traditional herbal formula that has been used to promote brain health. It consists of a 1:1:1 ratio of the aerial part of Centella asiatica, Piper nigrum fruit, and the petals of Nelumbo nucifera. According to the pharmacological activities of the individual medicinal plants, KBD has good potential as a treatment for MDD. The present study investigated the antidepressant activity of KBD in an unpredictable chronic mild stress (UCMS) mouse model. Daily administration of KBD to UCMS mice ameliorated both anhedonia, by increasing 2% sucrose intake, and hopeless behavior, by reducing immobility times in the forced swimming test (FST) and tail suspension test (TST) without any effect on locomotor activity. The mechanism of KBD activity was multi-modal. KBD promoted neurogenesis by upregulation of brain-derived neurotrophic factor (BDNF) and cyclic AMP-responsive element binding (CREB) mRNA expression in the frontal cortex and hippocampus. Daily treatment with KBD significantly reversed UCMS-induced HPA axis dysregulation by upregulating the glucocorticoid receptor (GR) while downregulating serum- and glucocorticoid-inducible kinase 1 (SGK1) and FK506 binding protein 5 (FKBP5) mRNA expression. KBD treatment also normalized proinflammatory cytokine expression including tumor necrosis factor-alpha (TNF-α), and interleukin (IL)-1β and IL-6. KBD and its component extracts also exhibited an inhibitory effect in vitro on monoamine oxidase (MAO) A and B. The multiple antidepressant actions of KBD emphasize its potential as an effective, novel treatment for MDD.
Robot-Assisted Gait Training in Patients with Multiple Sclerosis: A Randomized Controlled Crossover Trial

Background and Objectives: Gait disorders represent one of the most disabling aspects in multiple sclerosis (MS) that strongly influence patient quality of life. The improvement of walking ability is a primary goal for rehabilitation treatment. The aim of this study is to evaluate the effectiveness of robot-assisted gait training (RAGT) in association with physiotherapy treatment in patients affected by MS in comparison with ground conventional gait training. Study design: Randomized controlled crossover trial. Materials and Methods: Twenty-seven participants affected by MS with EDSS scores between 3.5 and 7 were enrolled, of whom seventeen completed the study. They received five training sessions per week over five weeks of conventional gait training with (experimental group) or without (control group) the inclusion of RAGT. The patients were prospectively evaluated before and after the first treatment session and, after the crossover phase, before and after the second treatment session. The evaluation was based on the 25-foot walk test (25FW, main outcome), 6 min walk test (6MWT), Tinetti Test, Modified Ashworth Scale, and modified Motricity Index for lower limbs. We also measured disability parameters using Functional Independence Measure and Quality of Life Index, and instrumental kinematic and gait parameters: knee extensor strength, double-time support, step length ratio; 17 patients reached the final evaluation. Results: Both groups significantly improved on gait parameters, motor abilities, and autonomy recovery in daily living activities with generally better results of RAGT over control treatment. In particular, the RAGT group improved more than control group in the 25FW (p = 0.004) and the 6MWT (p = 0.022). Conclusions: RAGT is a valid treatment option that in association with physiotherapy could induce positive effects in MS-correlated gait disorders. Our results showed greater effectiveness in recovering gait speed and resistance than conventional gait training.
Marine n-3 Polyunsaturated Fatty Acids and Bone Mineral Density in Kidney Transplant Recipients: A Randomized, Placebo-Controlled Trial

Kidney transplant recipients are at high risk of progressive bone loss and low-energy fractures in the years following transplantation. Marine n-3 polyunsaturated fatty acids (n-3 PUFA) supplementation may have beneficial effects on bone strength. The Omega-3 fatty acids in Renal Transplantation (ORENTRA) trial was an investigator initiated, randomized, placebo-controlled trial investigating the effects of marine n-3 PUFA supplementation after kidney transplantation. Effects of supplementation on bone mineral density (BMD) and calcium metabolism were pre-defined secondary endpoints. Adult kidney transplant recipients (n = 132) were randomized to 2.6 g marine n-3 PUFA supplement or olive oil (control) from 8 to 52 weeks post-transplant. Dual energy X-ray absorptiometry was performed to assess changes in bone mineral density of hip, spine, and forearm, as well as trabecular bone score (TBS) of the lumbar spine. Student’s t test was used to assess between-group differences. There were no differences in ΔBMD between the two groups (intervention vs. control) at lumbar spine (−0.020 ± 0.08 vs. −0.007 ± 0.07 g/cm², p = 0.34), total hip (0.001 ± 0.03 vs. −0.005 ± 0.04, p = 0.38), or other skeletal sites in the intention-to-treat analyses. There was no difference in the change in TBS score (0.001 ± 0.096 vs. 0.009 ± 0.102, p = 0.62). Finally, no effect on biochemical parameters of mineral metabolism was seen. Results were similar when analyzed per protocol. In conclusion, we found no significant effect of 44 weeks of supplementation with 2.6 g of marine n-3 PUFA on BMD in kidney transplant recipients.
Bridging the B Cell Gap: Novel Technologies to Study Antigen-Specific Human B Cell Responses

The generation of high affinity antibodies is a crucial aspect of immunity induced by vaccination or infection. Investigation into the B cells that produce these antibodies grants key insights into the effectiveness of novel immunogens to induce a lasting protective response against endemic or pandemic pathogens, such as influenza viruses, human immunodeficiency virus, or severe acute respiratory syndrome coronavirus-2. However, humoral immunity has largely been studied at the serological level, limiting our knowledge on the specificity and function of B cells recruited to respond to pathogens. In this review, we cover a number of recent innovations in the field that have increased our ability to connect B cell function to the B cell repertoire and antigen specificity. Moreover, we will highlight recent advances in the development of both ex vivo and in vivo models to study human B cell responses. Together, the technologies highlighted in this review can be used to help design and validate new vaccine designs and platforms.
Ciliary Signalling and Mechanotransduction in the Pathophysiology of Craniosynostosis

Craniosynostosis (CS) is the second most prevalent inborn craniofacial malformation; it results from the premature fusion of cranial sutures and leads to dimorphisms of variable severity. CS is clinically heterogeneous, as it can be either a sporadic isolated defect, more frequently, or part of a syndromic phenotype with mendelian inheritance. The genetic basis of CS is also extremely heterogeneous, with nearly a hundred genes associated so far, mostly mutated in syndromic forms. Several genes can be categorised within partially overlapping pathways, including those causing defects of the primary cilium. The primary cilium is a cellular antenna serving as a signalling hub implicated in mechanotransduction, housing key molecular signals expressed on the ciliary membrane and in the cilioplasm. This mechanical property mediated by the primary cilium may also represent a cue to understand the pathophysiology of non-syndromic CS. In this review, we aimed to highlight the implication of the primary cilium components and active signalling in CS pathophysiology, dissecting their biological functions in craniofacial development and in suture biomechanics. Through an in-depth revision of the literature and computational annotation of disease-associated genes we categorised 18 ciliary genes involved in CS aetiology. Interestingly, a prevalent implication of midline sutures is observed in CS ciliopathies, possibly explained by the specific neural crest origin of the frontal bone.
Progression of Postprandial Blood Plasma Phospholipids Following Acute Intake of Different Dairy Matrices: A Randomized Crossover Trial

Studies have indicated that the dairy matrix can affect postprandial responses of dairy products, but little is known about the effect on postprandial plasma phospholipid levels. This study investigated postprandial plasma phospholipid levels following consumption of four different dairy products that are similar in micro and macro nutrients, but different in texture and structure: cheddar cheese (Cheese), homogenized cheddar cheese (Hom. Cheese), micellar casein isolate with cream (MCI Drink) or a gel made from the MCI Drink (MCI Gel). The study was an acute randomized, crossover trial in human volunteers with four test days. Blood samples were collected during an 8 h postprandial period and the content of 53 plasma phospholipids was analysed using liquid chromatography-mass spectrometry (LC-MS). No meal–time interactions were revealed; however, for nine of the 53 phospholipids, a meal effect was found. Thus, the results indicated a lower plasma level of specific lyso-phosphatidylethanolamines (LPEs) and lyso-phosphatidylcholines (LPCs) following consumption of the MCI Gel compared to the MCI Drink and Hom. Cheese, which might be attributed to an effect of viscosity. However, further studies are needed in order to reveal more details on the effect of the dairy matrix on postprandial phospholipids.
The Role of Macrophages in the Host’s Defense against Sporothrix schenckii

The role of immune cells associated with sporotrichosis caused by Sporothrix schenckii is not yet fully clarified. Macrophages through pattern recognition receptors (PRRs) can recognize pathogen-associated molecular patterns (PAMPs) of Sporothrix, engulf it, activate respiratory burst, and secrete pro-inflammatory or anti-inflammatory biological mediators to control infection. It is important to consider that the characteristics associated with S. schenckii and/or the host may influence macrophage polarization (M1/M2), cell recruitment, and the type of immune response (1, 2, and 17). Currently, with the use of new monocyte-macrophage cell lines, it is possible to evaluate different host–pathogen interaction processes, which allows for the proposal of new mechanisms in human sporotrichosis. Therefore, in order to contribute to the understanding of these host–pathogen interactions, the aim of this review is to summarize and discuss the immune responses induced by macrophage-S. schenckii interactions, as well as the PRRs and PAMPs involved during the recognition of S. schenckii that favor the immune evasion by the fungus.
COVID-19: Failure of the DisCoVeRy Clinical Trial, and Now–New Hopes?

The DisCoVeRy clinical trial aimed at the evaluation of four treatments for patients suffering from severe to critical COVID-19: Hydroxychloroquine, eventually associated with azithromycin; the combination lopinavir/ritonavir; the combination with the addition of interferon β-1a; remdesivir. The trial was discontinued due to the lack of positive results. Meanwhile, many other potential options have been considered either to target the virus itself, the interactions with the host cells, or the cytokine storm frequently observed during the infection. Several of those options are briefly reviewed. They include vaccines, small molecules, antibodies, and stem cells.