Miracle-dz/UniFAR-FTUs huggingface dataset:
Augmented CD133 expression in distal margin correlates with poor prognosis in colorectal cancer

Pathological assessment of excised tumour and surgical margins in colorectal cancer (CRC) play crucial role in prognosis after surgery. Molecular assessment of margins could be more sensitive and informative than conventional histopathological analysis. Considering this view, we evaluated the distal surgical margins for expression of cancer stem cell (CSC) markers. Cellular and molecular assessment of normal, tumour and distal margin tissues were performed by flow cytometry, real‐time q‐PCR and immuno‐histochemical analysis for CRC patients after tumour excision. CRC patients were evaluated for expression of CSC markers in their normal, tumour and distal tissues. Flow cytometry assay revealed CD133 and CD44 enriched cells in distal margin and tumour compared to normal colorectal tissues, which was further confirmed by immunohistochemistry. Most importantly, immunohistochemistry also revealed the enrichment of CSC markers expression in pathologically negative distal margins. Patients with distal margin enriched for CD133 expression showed an increased recurrence rate and decreased disease‐free survival. This study proposes that although distal margin seems to be tumour free in conventional histopathological analysis, it could harbour cells enriched for CSC markers. Further CD133 could be a promising molecule to be used in molecular pathology for disease prognosis after surgery in CRC patients.
Les fausses nouvelles et les attaques des négateurs scientifiques contre les vaccins. Que pouvez-vous faire?

La mésinformation et la désinformation (« fausses nouvelles ») sur les vaccins sont contagieuses : elles se déplacent plus vite et plus loin que la vérité. Les conséquences sont graves, menant à des effets négatifs sur les décisions en matière de santé, y compris l’acceptation des vaccins, et sur la confiance dans les conseils d’immunisation fournis par les professionnels de la santé publique ou des soins de santé. Le présent article donne un aperçu des stratégies fondées sur des données probantes pour traiter les négateurs du vaccin en public, en pratique clinique et dans des situations sociales. De plus, une stratégie visant à aider à différencier les négateurs du vaccin et les personnes qui refusent simplement un vaccin dans une clinique ou une pratique est fournie. Cinq tactiques sont largement utilisées par les négateurs des vaccins : complots; faux experts; sélectivité; attentes impossibles; et fausse représentation et fausse logique. La reconnaissance et la compréhension de ces tactiques peuvent contribuer à protéger contre la désinformation et la propagande négationniste scientifique. Mettre en évidence le consensus solide des sciences médicales sur l’innocuité et l’efficacité des vaccins est également utile. Il est crucial de choisir avec soin et sagesse ce qu’il faut dire, et vous exprimer, que vous soyez à un dîner, avec des amis ou dans votre clinique ou cabinet médical. Ne pas vous exprimer suggère que vous êtes d’accord avec la mésinformation. Il est de plus en plus important que les fournisseurs de soins de santé reconnaissent et traitent la mésinformation en utilisant des stratégies fondées sur des données probantes, car l’arrivée des vaccins contre la maladie à coronavirus de 2019 (COVID-19) devrait intensifier encore la rhétorique de mésinformation et de désinformation sur les vaccins. Les fournisseurs de soins de santé doivent se préparer et agir dès maintenant pour lutter contre le tsunami de la mésinformation vaccinale. Affiliation
Impact factors that modulate gastric cancer risk in Helicobacter pylori‐infected rodent models

Gastric cancer causes a large social and economic burden to humans. Helicobacter pylori (H pylori) infection is a major risk factor for distal gastric cancer. Detailed elucidation of H pylori pathogenesis is significant for the prevention and treatment of gastric cancer. Animal models of H pylori‐induced gastric cancer have provided an invaluable resource to help elucidate the mechanisms of H pylori‐induced carcinogenesis as well as the interaction between host and the bacterium. Rodent models are commonly used to study H pylori infection because H pylori‐induced pathological processes in the stomachs of rodents are similar to those in the stomachs of humans. The risk of gastric cancer in H pylori‐infected animal models is greatly dependent on host factors, bacterial determinants, environmental factors, and microbiota. However, the related mechanisms and the effects of the interactions among these impact factors on gastric carcinogenesis remain unclear. In this review, we summarize the impact factors mediating gastric cancer risk when establishing H pylori‐infected animal models. Clarifying these factors and their potential interactions will provide insights to construct animal models of gastric cancer and investigate the in‐depth mechanisms of H pylori pathogenesis, which might contribute to the management of H pylori‐associated gastric diseases.
The effect of dietary vitamin D supplementation on sodium-dependent phosphate uptake and expression of NaPi-IIb in the small intestine of weanling pigs.

Two experiments were conducted to investigate the effects of 1,25(OH)2D3 to stimulate Na+-dependent phosphate uptake in Caco-2 cells, and the effects of dietary vitamin D supplementation to vitamin D-deficient nursery pigs on Na+-dependent nutrient uptake and mRNA expression of NaPi-IIb cotransporter and calbindin D(9k) in the jejunum. In Exp. 1, 250,000 Caco-2 cells were seeded on Costar 12 mm Snapwell inserts with a 0.40 µm polycarbonate filter and a seeding density of 0.25 × 106 and studied at 15 d postconfluence. Cells were treated with 10 nM of either 1,25(OH)2D3 or vehicle for 48 h and then mounted in modified Ussing chambers for transepithelial measurements. In Exp. 2, pigs (n=32) were removed from sows at 3 d of age, placed on a vitamin D-deficient milk replacer diet and housed in a room devoid of sunlight and UV light in the range of 280 to 300nm. On d 28, serum 25(OH)D3 concentrations were measured to verify low vitamin D status. Pigs (BW 10.10 ± 0.38 kg) were then individually housed d 28 post-weaning and allotted to 1 of 2 dietary treatments. Dietary treatments consisted of corn-soybean based diets with vitamin D supplementations of 0 or 1,500 IU/kg diet for 12 d. Blood samples were taken from the brachiocephalic vein on the initial (d 0) and final day (d 10,11, or 12) of the study for analysis of serum 25(OH)D3 , P, and Ca. Pigs were euthanized and jejunal segments were harvested and used in modified Ussing chambers and for RNA isolation and subsequent quantitative RT-PCR analysis. In Exp. 1, treating Caco-2 cells with 10 nM 1,25(OH)2D3 resulted in a 52% increase (P < 0.005) in Na+-dependent phosphate uptake compared with cells treated with a vehicle. In Exp. 2, Na+-dependent phosphate and glucose transport did not differ (P > 0.10) among treatment groups. Additionally, NaPi-IIb and calbindin D(9k) mRNA expression were not different (P > 0.10) between treatment groups. No differences (P > 0.10) were detected in final serum P or 25(OH)D3 concentrations between treatments. However, serum Ca linearly increased (P < 0.05) as the concentration of supplemental vitamin D increased in the diet. Overall, while 1,25(OH)2D3 stimulated Na+-dependent phosphate uptake in Caco-2 cells, supplementing diets with 1,500 IU/kg Vitamin D3 from cholecalciferol did not increase jejunal Na+-dependent phosphate uptake or NaPi-IIb mRNA expression over that of pigs fed diets with no supplemental cholecalciferol.
PD-1, TIM-3, and LAG-3 Expression in T Cells in a Patient with Recurrent Ossifying Fibroma: A Case Report

Central ossifying fibroma is a benign, slow-growing tumor of mesenchymal origin with a predilection for the mandibular premolar and molar areas. The immunophenotype of T cells involved in the antitumor response against this benign tumor is unknown. In this case report, we described a case of a 48-year-old woman presenting with a very large recurrent ossifying fibroma in the mandible, which was successfully treated with hemimaxillectomy. In addition, we evaluated the expression of programmed cell death 1 receptor (PD-1), lymphocyte activation gene-3 (LAG-3), T cell immunoglobulin and mucin-domain containing-3 (TIM-3), cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), CD69 (activation inducer molecule), and CD25 (α chain of the high-affinity IL-2 receptor) in T cell populations from the tumor and peripheral blood of this uncommon lesion. The patient presented recurrent ossifying fibroma, and the tumor-infiltrating and peripheral blood T cells showed expression of PD-1, LAG-3, and TIM-3, suggesting an exhausted T cell response.
Siculibacillus lacustris gen. nov., sp. nov., a new rosette-forming bacterium isolated from a freshwater crater lake (Lake St. Ana, Romania).

A new aerobic alphaproteobacterium, strain SA-279T, was isolated from a water sample of a crater lake. The 16S rRNA gene sequence analysis revealed that strain SA-279T formed a distinct lineage within the family Ancalomicrobiaceae and shared the highest pairwise similarity values with Pinisolibacterravus E9T (96.4 %) and Ancalomicrobiumadetum NBRC 102456T (94.2 %). Cells of strain SA-279T were rod-shaped, motile, oxidase and catalase positive, and capable of forming rosettes. Its predominant fatty acids were C18 : 1ω7c (69.0 %) and C16 : 1ω7c (22.7 %), the major respiratory quinone was Q-10, and the main polar lipids were phosphatidylethanolamine, phosphatidylmonomethylethanolamine, phosphatidylcholine, phosphatidylglycerol, an unidentified aminophospholipid and an unidentified lipid. The G+C content of the genomic DNA of strain SA-279T was 69.2 mol%. On the basis of the phenotypic, chemotaxonomic and molecular data, strain SA-279T is considered to represent a new genus and species within the family Ancalomicrobiaceae, for which the name Siculibacillus lacustris gen. nov., sp. nov. is proposed. The type strain is SA-279T (=DSM 29840T=JCM 31761T).
Increased blood pressure is associated with increased carotid artery intima-media thickness in children with repaired coarctation of the aorta.

OBJECTIVES The intima-media thickness of the common carotid artery (cIMT) is a good noninvasive surrogate marker for cardiovascular disease. Regular cIMT monitoring in children with congenital heart disease has great potential. We sought to determine which anthropomorphic and haemodynamic variables were significantly associated with the cIMT in paediatric patients with obesity and children with repaired coarctation of the aorta (CoA). METHODS We measured the cIMT in 143 children aged 5 to less than 18 years including normal weight controls (n = 44), children with overweight/obesity (n = 73) and children with repaired CoA (n = 26). cIMT was compared and the association between the cIMT and patient characteristics, including obesity and blood pressure (BP), was investigated. RESULTS BMI z score, sex and the presence of CoA were significant independent predictors of cIMT. The cIMT was significantly greater in children with overweight/obesity (0.53 ± 0.06 mm) relative to normal weight controls (0.51 ± 0.04 mm), as well as in CoA patients with abnormally high BP (0.57 ± 0.08 mm) versus CoA patients with normal BP (0.52 ± 0.05 mm) and controls (0.51 ± 0.04 mm). CoA patients with normal BP did not have significantly increased cIMT. CONCLUSION cIMT was positively associated with BMI z score, male sex and CoA repair in children. The increased cIMT in children with repaired CoA was because of those with abnormally high BP, which was masked in clinic for most of these patients. These findings warrant further investigations into the cIMT and other atherosclerotic risk factors to determine their potential clinical impact in these highly susceptible patients.
Oral administration of oyster (Crassostrea gigas) hydrolysates protects against wrinkle formation by regulating the MAPK pathway in UVB-irradiated hairless mice

Chronic ultraviolet (UV) irradiation induces wrinkle formation. UV exposure increases reactive oxygen species (ROS) and upregulates the expression of matrix metalloproteinases (MMPs), which results in skin photoaging. Oyster ( Crassostrea gigas ), which is an abundant food resource in Asia and Europe, contains various sources of biological compounds and has several effects. Also, oyster hydrolysate (OH) has many biological activities. We investigated the inhibitory effects of OH on wrinkle formation in UVB-irradiated hairless mice. We induced UVB irradiation in hairless mice for 18 weeks and administered OH orally from the 9^th week to the 18^th week. We performed skin replicas and histological analyses in UVB-irradiated hairless mice dorsal skins. To determine the inhibitory mechanism of OH on wrinkle formation, we measured gene and protein expressions in dorsal skin using RT-qPCR and western blot analyses respectively. In our study, OH decreases wrinkle formation, epidermal thickness and collagen degradation in UVB-irradiated hairless mice. The gene expressions of MMPs were decreased and the gene expressions of collagen type I and TIMP-1 were increased in OH administered groups. Like gene expression tendencies, the protein expressions of MMPs were reduced and that of collagen type I was increased. Furthermore, the phosphorylation levels of ERK, JNK, and p38 were reduced in OH administered groups. We found that OH inhibits wrinkle formation, skin thickening, and collagen degradation by downregulating the MMP expression via the regulation of phosphorylation of MAPK. The results showed that OH significantly prevents UVB-induced photoaging in dorsal skin. Consistent with in vivo data, OH has potential as an anti-wrinkle agent.
Electromyographic Changes in the Masseter and Temporalis Muscles Before and After Orthognathic Surgery in Patients With Mandibular Prognathism.

OBJECTIVE Evaluate the electromyographic changes in the Masseter (MM) and Temporalis (TM) muscles during voluntary clenching of the teeth both before and after orthognathic surgery in patients aged 18 years and older and diagnosed with mandibular prognathism. METHODS Eleven patients with prognathism were included in the study, in all of whom the initial phase of orthodontic treatment had been completed. The orthognathic procedure to reduce prognathism comprised intraoral oblique sliding (or subsigmoid) osteotomy, after which intermaxillary fixation with ligaments in the maxilla and mandible was undertaken in all patients for 6 weeks post-surgery. Electromyographic activity was recorded during the baseline maximum voluntary contraction of the teeth, with the same measurement taken 3 and then 6 months after orthognathic surgery. RESULTS Significant differences were found in the mean amplitude (17.0 vs 14.7, P = 0.020) and peak-to-peak amplitude (left [761.6 vs 457.0, P = 0.003] and right [676.9 vs 357.4, P = 0.007]) for the MM between the baseline score and 6 months after surgery. Likewise, significant differences were found in the mean amplitude (18.2 vs 25.6, P = 0.009) and peak-to-peak amplitude (left [856.4 vs 1594.2, P = 0.004] and right [804.4 vs 1813.4, P = 0.004]) for the TM between the baseline score and that taken 6 months post-surgery. Only 18.2% (2/11) presented orthodontic appliances problem in the 3 months post-surgery. CONCLUSION Electromyographic activity was restored 6 months after the orthognathic surgery. From a clinical perspective, the results obtained confirm that orthognathic surgery has not only an esthetic but also a functional objective in terms of achieving equilibrium and occlusal harmony.
Activation of the STAT3/microRNA‐21 pathway participates in angiotensin II‐induced angiogenesis

Angiotensin II (AngII) facilitates angiogenesis that is associated with the continuous progression of atherosclerotic plaques, but the underlying mechanisms are still not fully understood. Several microRNAs (miRNAs) have been shown to promote angiogenesis; however, whether miRNAs play a crucial role in AngII‐induced angiogenesis remains unclear. This study evaluated the functional involvement of miRNA‐21 (miR‐21) in the AngII‐mediated proangiogenic response in human microvascular endothelial cells (HMECs). We found that AngII exerted a proangiogenic role, indicated by the promotion of proliferation, migration, and tube formation in HMECs. Next, miR‐21 was found to be upregulated in AngII‐treated HMECs, and its specific inhibitor potently blocked the proangiogenic effects of AngII. Subsequently, we focused on the constitutive activation of STAT3 in the AngII‐mediated proangiogenic process. Bioinformatic analysis indicated that STAT3 acted as a transcription factor initiating miR‐21 expression, which was verified by ChIP‐PCR. A reporter assay further identified three functional binding sites of STAT3 in the miR‐21 promoter region. Moreover, phosphatase and tensin homolog (PTEN) was recognized as a target of miR‐21, and STAT3 inhibition restored AngII‐induced reduction in PTEN. Similarly, the STAT3/miR‐21 axis was shown to mediate AngII‐provoked angiogenesis in vivo, which was demonstrated by using the appropriate inhibitors. Our data suggest that AngII was involved in proangiogenic responses through miR‐21 upregulation and reduced PTEN expression, which was, at least in part, linked to STAT3 signaling. The present study provides novel insights into AngII‐induced angiogenesis and suggests potential treatment strategies for attenuating the progression of atherosclerotic lesions and preventing atherosclerosis complications.
A Smart IoT System for Detecting the Position of a Lying Person Using a Novel Textile Pressure Sensor

Bedsores are one of the severe problems which could affect a long-term lying subject in the hospitals or the hospice. To prevent lying bedsores, we present a smart Internet of Things (IoT) system for detecting the position of a lying person using novel textile pressure sensors. To build such a system, it is necessary to use different technologies and techniques. We used sixty-four of our novel textile pressure sensors based on electrically conductive yarn and the Velostat to collect the information about the pressure distribution of the lying person. Using Message Queuing Telemetry Transport (MQTT) protocol and Arduino-based hardware, we send measured data to the server. On the server side, there is a Node-RED application responsible for data collection, evaluation, and provisioning. We are using a neural network to classify the subject lying posture on the separate device because of the computation complexity. We created the challenging dataset from the observation of twenty-one people in four lying positions. We achieved a best classification precision of 92% for fourth class (right side posture type). On the other hand, the best recall (91%) for first class (supine posture type) was obtained. The best F1 score (84%) was achieved for first class (supine posture type). After the classification, we send the information to the staff desktop application. The application reminds employees when it is necessary to change the lying position of individual subjects and thus prevent bedsores.
Tissue engineering for paediatric patients.

The effects of oncological treatment, congenital anomalies, traumatic injuries and post-infection damage critically require sufficient amounts of tissue for structural and functional surgical reconstructions. The patient’s own body is typically the gold standard source of transplant material, but in children autologous tissue is available only in small quantities and with severe morbidity at donor sites. Engineering of tissue grafts starting from a small amount of autologous material, combined with suitable surgical manipulation of the recipient site, is expected to enhance child and adolescent health, and to offer functional restoration for long-term wellbeing. Moreover, engineered tissues based on patient-derived cells represent invaluable models to investigate mechanisms of disease and to develop/test novel therapeutic approaches. In view of these great opportunities, here we introduce the currently limited successful implementation of tissue engineering in paediatric settings and discuss the open challenges in the field. A particular focus is on the specific needs and envisioned strategies in the areas of bone and osteochondral regeneration in children.
DDRE-28. EGFR INHIBITION DOWNREGULATES MGMT AND SENSITIZES GBM CELLS TO TMZ

Glioblastoma (GBM) is a highly malignant type of adult brain tumor with a poor prognosis. Temozolomide (TMZ), a DNA alkylating agent, has been widely used as an effective first-line chemotherapeutic agent for the treatment of GBM patients. The efficacy of TMZ in GBM depends on the absence of the DNA repair protein MGMT which reverses the DNA damage induced by TMZ. The MGMT promoter is hypermethylated in about 45% of GBMs, resulting in lack of MGMT expression and increased responsiveness to TMZ. TMZ is less effective in MGMT unmethylated GBMs. We propose that EGFR inhibition downregulates MGMT and sensitizes glioma cells to TMZ and a combination of pretreatment with erlotinib followed by TMZ could be a useful therapeutic approach in MGMT expressing GBMs. As our experimental model we used multiple MGMT unmethylated lines from the Mayo Clinic patient derived xenografts (PDXs) panel. Our data demonstrate that exposure of cells to EGFR tyrosine kinase inhibitor erlotinib for 48h results in downregulation of MGMT at the mRNA and protein level. Additionally, EGFR inhibition activates the AP-1 transcription factor and overexpression of AP-1 components Fos and Jun results in decreased MGMT expression in TMZ resistant PDXs, suggesting that AP-1 acts as a transcriptional repressor of MGMT. We further identified that the mice implanted with TMZ resistant PDXs pretreated with afatinib followed by TMZ treatment survived longer compared to those treated with TMZ alone. Thus, the use of EGFR inhibition may enhance the sensitivity of MGMT unmethylated GBMs to TMZ.
Prognostic value of automated pupillometry: an unselected cohort from a cardiac intensive care unit

Background: Patients admitted to a cardiac intensive care unit are often unconscious with uncertain prognosis. Automated infrared pupillometry for neurological assessment in the intensive care unit may provide early prognostic information. This study aimed to determine the prognostic value of automated pupillometry in different subgroups of patients in a cardiac intensive care unit with 30-day mortality as the primary endpoint and neurological outcome as the secondary endpoint. Methods: A total of 221 comatose patients were divided into three groups: out-of-hospital cardiac arrest, in-hospital cardiac arrest and others (i.e. patients with cardiac diagnoses other than cardiac arrest). Automated pupillometry was serially performed until discharge or death and pupil measurements were analysed using the neurological pupil index algorithm. We applied receiver operating characteristic curves in univariable and multivariable logistic regression models and a calculated Youden index identified neurological pupil index cut-off values at different specificities. Results: In out-of-hospital cardiac arrest patients higher neurological pupil index values were independently associated with lower 30-day mortality. The univariable model for 30-day mortality had an area under the curve of 0.87 and the multivariable model achieved an area under the curve of 0.94. The Youden index identified a neurological pupil index cut-off in out-of-hospital cardiac arrest patients of 2.40 for a specificity of 100%. For patients with in-hospital cardiac arrest and other cardiac diagnoses, we found no association between neurological pupil index values and 30-day mortality, and the univariable models showed poor predictive values. Conclusion: Automated infrared pupillometry has promising predictive value after out-of-hospital cardiac arrest, but poor predictive value in patients with in-hospital cardiac arrest or cardiac diagnoses unrelated to cardiac arrest. Our data suggest a possible neurological pupil index cut-off of 2.40 for poor outcome in out-of-hospital cardiac arrest patients.