Miracle-dz/UniFAR-FTUs huggingface dataset:
miR‐196b‐5p inhibits proliferation of Wharton's jelly umbilical cord stem cells

Human umbilical cord mesenchymal stem cells can be obtained from different parts of the umbilical cord, including Wharton's jelly. Transplantation of Wharton's jelly umbilical cord stem cells (WJCMSCs) is a promising strategy for the treatment of various diseases. However, the molecular mechanisms underlying the proliferation of WJCMSCs are incompletely understood. Here, we report that overexpression of miR‐196b‐5p in WJCMSCs suppresses proliferation and arrests the cell cycle in G0/G1 phase, whereas knockdown of miR‐196b‐5p promotes WJCMSC proliferation and cell‐cycle progression. Moreover, miR‐196b‐5p overexpression resulted in decreased levels of Cyclin A, Cyclin D, Cyclin E and cyclin‐dependent kinases 2 and increased levels of p15INK4b, whereas miR‐196b‐5p knockdown had the opposite effects. In conclusion, our data suggests that miR‐196b‐5p inhibits WJCMSC proliferation by enhancing G0/G1‐phase arrest.
Low Dose CT Image and Projection Dataset.

PURPOSE To describe a large, publicly available dataset comprising CT projection data from patient exams, both at routine clinical doses and simulated lower doses. ACQUISITION AND VALIDATION METHODS The library was developed under local ethics committee approval. Projection and image data from 299 clinically-performed patient CT exams were archived for three types of clinical exams: non-contrast head CT scans acquired for acute cognitive or motor deficit, low-dose non-contrast chest scans acquired to screen high-risk patients for pulmonary nodules, and contrast-enhanced CT scans of the abdomen acquired to look for metastatic liver lesions. Scans were performed on CT systems from two different CT manufacturers using routine clinical protocols. Projection data were validated by reconstructing the data using several different reconstruction algorithms and through use of the data in the 2016 Low Dose CT Grand Challenge. Reduced dose projection data were simulated for each scan using a validated noise-insertion method. Radiologists marked location and diagnosis for detected pathologies. Reference truth was obtained from the patient medical record, either from histology or subsequent imaging. DATA FORMAT AND USAGE NOTES Projection datasets were converted into the previously developed DICOM-CT-PD format, which is an extended DICOM format created to store CT projections and acquisition geometry in a non-proprietary format. Image data are stored in the standard DICOM image format and clinical data in a spreadsheet. Materials are provided to help investigators use the DICOM-CT-PD files, including a dictionary file, data reader and user manual. The library is publicly available from The Cancer Imaging Archive (https://doi.org/10.7937/9npb-2637). POTENTIAL APPLICATIONS This CT data library will facilitate the development and validation of new CT reconstruction and/or denoising algorithms, including those associated with machine learning or artificial intelligence. The provided clinical information allows evaluation of task-based diagnostic performance.
Vertical Bone Gain after Sinus Lift Procedures with Beta-Tricalcium Phosphate and Simultaneous Implant Placement—A Cross-Sectional Study

Objectives: The objective of this cross-sectional study was to evaluate the vertical bone gain achieved after the sinus lift procedure with beta-tricalcium phosphate (β-TCP) used as a bone substitute and simultaneous implant placement. Methods: One hundred and twenty-eight sinus lift procedures (utilizing a synthetic ceramic containing 99.9% tricalcium phosphate as a bone substitute) and simultaneous implant placements were performed on 119 patients. The lateral window approach surgical protocol for maxillary sinus lift was performed on the patients. The implants were evaluated using cone-beam computed tomography (CBCT) at 6 months following placement. The vertical bone gain was considered a primary variable, while implant length, diameter, and location were considered secondary variables. Results: The ANOVA results showed no statistical difference in vertical bone gain with implant parameters like implant length, width, and position. Pearsons correlation revealed a statistically significant positive correlation with vertical bone gain and implant length and diameter. A further multivariate linear regression analysis was performed and it observed statistically significant associations between the variables in the study after adjusting for confounding factors. Conclusions: This study concluded that there was vertical bone gain with the usage of β-TCP in maxillary sinus lift surgical procedure with immediate implant placement and that implant variables like length and diameter had a significant influence on the average bone gain values. The implant position did not have a statistically significant influence but there was considerable variation in the bone gain between first, second premolar, and molar regions.
Chlamydia pecorum–Associated Sporadic Ovine Abortion

Despite previous detection of Chlamydia pecorum in sporadic ovine abortions, published descriptions of naturally occurring infections with fetoplacental lesions are lacking. This report provides the first descriptions of severe necrosuppurative chorionitis with vasculitis, and fetal pyelonephritis and enteritis in late-term abortions of maiden ewes. Chlamydial infection was detected using a Chlamydia genus-specific qPCR (quantitative polymerase chain reaction) on tissue extracts from 3 fetuses. C. pecorum was identified using a targeted qPCR assay, which also determined infectious load within fetal tissues. The presence of viable C. pecorum in fetal samples was confirmed by cell culture. Multilocus sequence typing (MLST) data indicated that the C. pecorum strains from each fetus were identical and of sequence type (ST) 23. Chlamydia sp. immunohistochemistry showed strong positive immunolabeling of fetoplacental lesions. Other infectious abortigenic agents were excluded with specific testing. This report confirms C. pecorum as a likely cause of ovine abortion and provides the first descriptions of associated fetoplacental lesions in naturally infected sheep.
Atypical Inter‐Network Deactivation Associated With the Posterior Default‐Mode Network in Autism Spectrum Disorder

Previous studies have suggested that atypical deactivation of functional brain networks contributes to the complex cognitive and behavioral profile associated with autism spectrum disorder (ASD). However, these studies have not considered the temporal dynamics of deactivation mechanisms between the networks. In this study, we examined (a) mutual deactivation and (b) mutual activation‐deactivation (i.e., anticorrelated) time‐lag patterns between resting‐state networks (RSNs) in young adults with ASD (n = 20) and controls (n = 20) by applying the recently defined dynamic lag analysis (DLA) method, which measures time‐lag variations peak‐by‐peak between the networks. In order to achieve temporally accurate lag patterns, the brain imaging data was acquired with a fast functional magnetic resonance imaging (fMRI) sequence (TR = 100 ms). Group‐level independent component analysis was used to identify 16 RSNs for the DLA. We found altered mutual deactivation timings in ASD in (a) three of the deactivated and (b) two of the transiently anticorrelated (activated‐deactivated) RSN pairs, which survived the strict threshold for significance of surrogate data. Of the significant RSN pairs, 80% included the posterior default‐mode network (DMN). We propose that temporally altered deactivation mechanisms, including timings and directionality, between the posterior DMN and RSNs mediating processing of socially relevant information may contribute to the ASD phenotype.
Occurrence of milk and egg allergens in foodstuffs in Canada

ABSTRACT Food allergies are life-threatening conditions that allergic individuals can avoid by consulting the food labels before consuming. Precautionary allergen labelling (or PAL), to warn against possible allergen cross-contamination, is widely used by food industries, reducing the food choices for allergic individuals. In Canada, there is limited information on the actual occurrence of allergens in products with a PAL related to the given allergen. This study attempted to fill the data gap by evaluating the occurrence of milk and egg allergens in Canadian products with PAL. A total of 1125 samples were analysed for milk and 840 for eggs, with 23% and 7% of these samples showing positive detection of ≥2.5 mg kg−1 for milk and ≥0.245 mg kg−1 for eggs. Chocolate products gave the largest number of positive results. Although the proportion of positive results was low, the levels detected reached 6471 mg kg−1 in a chocolate sample and were indicative of possible health consequences, if PAL was ignored by allergic consumers. The occurrence data generated is destinated to be used in exposure and risk assessments, to support allergen management linked to cross-contamination, with the possible development of allergen action levels that would be used by food industries, thus improving a risk-based approach for the application of PAL.
A multidisciplinary investigation into “playing-up” in academy football according to age phase

ABSTRACT In an attempt to facilitate more appropriate levels of challenge, a common practice in academy football is to play-up talented youth players with chronologically older peers. However, the context of playing-up in academy football is yet to be empirically explored. Thus, the purpose of this study was to examine the multidimensional factors that differentiated players who play-up from those who do not. Ninety-eight participants from a single football academy were examined within their age phase: Foundation Development Phase (FDP; under-9 to under-11; n = 40) and Youth Development Phase (YDP; under-12 to under-16; n = 58). Drawing upon the FA Four Corner Model, 27 factors relating to Technical/Tactical, Physical, Psychological, and Social development were assessed. Following MANOVA analysis within both the FDP and YDP, significant differences were observed for Technical/Tactical and Social sub-components (P < 0.05). Further differences were observed for Physical and Psychological sub-components (P < 0.05) within the YDP. In sum, Technical/Tactical and Social characteristics appeared to differentiate those who play-up compared to those who do not within the FDP. In the YDP however, there were measures representing all sub-components from the FA Four Corner Model. Subsequently, it is suggested coaches and practitioners consider these holistic factors when playing-up youth football players within relevant age-phases.
Presynaptic Vesicle Protein SEPTIN5 Regulates the Degradation of APP C-Terminal Fragments and the Levels of Aβ

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by aberrant amyloid-β (Aβ) and hyperphosphorylated tau aggregation. We have previously investigated the involvement of SEPTIN family members in AD-related cellular processes and discovered a role for SEPTIN8 in the sorting and accumulation of β-secretase. Here, we elucidated the potential role of SEPTIN5, an interaction partner of SEPTIN8, in the cellular processes relevant for AD, including amyloid precursor protein (APP) processing and the generation of Aβ. The in vitro and in vivo studies both revealed that the downregulation of SEPTIN5 reduced the levels of APP C-terminal fragments (APP CTFs) and Aβ in neuronal cells and in the cortex of Septin5 knockout mice. Mechanistic elucidation revealed that the downregulation of SEPTIN5 increased the degradation of APP CTFs, without affecting the secretory pathway-related trafficking or the endocytosis of APP. Furthermore, we found that the APP CTFs were degraded, to a large extent, via the autophagosomal pathway and that the downregulation of SEPTIN5 enhanced autophagosomal activity in neuronal cells as indicated by altered levels of key autophagosomal markers. Collectively, our data suggest that the downregulation of SEPTIN5 increases the autophagy-mediated degradation of APP CTFs, leading to reduced levels of Aβ in neuronal cells.
Linking Circulating Serum Proteins with Clinical Outcomes in Esophageal Adenocarcinoma—An Emerging Role for Chemokines

Simple Summary Cancer of the esophagus (food pipe) is an aggressive type of cancer with poor prognosis and rates are increasing. Current treatments help to prolong survival but only for a minority of patients, therefore there is an urgent need to discover why some people do not respond and to develop new and improved treatments. Newer treatments targeting the immune system show promise but the anti-tumor immune response in esophageal cancer is not well understood. This study measured levels of 54 immune markers in serum of patients with esophageal cancer and evaluated a link with patient clinical outcomes, e.g., survival time, response to treatment, and adverse events. We found that certain chemokines, proteins which control immune cell trafficking, were particularly high in patients who survived longer (CCL22 and CCL26) and responded to treatment (CCL4), suggesting the importance of immune cell movement in orchestrating an effective immune response to esophageal cancer. Abstract Esophageal adenocarcinoma (EAC) is an aggressive cancer with poor prognosis and incidence is increasing rapidly in the Western world. Multi-modal treatment has improved survival outcomes but only for a minority of patients. Currently no markers have been identified to predict treatment response. This study investigated the association between clinical outcomes and pre-treatment levels of 54 serum proteins in n = 80 patients with EAC. Low tumor regression grade (TRG), corresponding to a favorable treatment response, was linked to prolonged overall survival (OS). CCL4 was higher in patients with a favorable treatment response, while Tie2 and CRP were higher in poor responders. Elevated CCL22 and CCL26 was associated with improved OS, while elevated IL-10 showed a negative association. CCL3, CCL4, IL-1α and IL-12/IL23p40 were highest in individuals with no adverse features of tumor biology, whereas levels of Tie2 and VEGF were lowest in this cohort. CCL4 was also elevated in patients with high tumor lymphocyte infiltration. Comparison of matched pre- and post-treatment serum (n = 28) showed a large reduction in VEGFC, and a concomitant increase in other cytokines, including CCL4. These data link several serum markers with clinical outcomes, highlighting an important role for immune cell trafficking in the EAC antitumor immune response.
Hepatoprotective and anti-inflammatory effects of a standardized pomegranate (Punica granatum) fruit extract in high fat diet-induced obese C57BL/6 mice

Abstract Diets rich in fats are linked to elevated systemic inflammation, which augments the progression of inflammatory-related disorders including non-alcoholic fatty liver disease (NAFLD) and neurodegenerative diseases. A phenolic-enriched pomegranate fruit extract (PE) was investigated for its hepatoprotective and anti-inflammatory effects in male C57BL/6 mice fed either a high-fat diet or a standard rodent diet with or without 1% of PE for 12 weeks. Mouse livers and hippocampi were evaluated for the expression of genes associated with NAFLD and inflammation by multiplexed gene analysis. PE alleviated diet-induced fatty liver and suppressed hepatic lipid regulating genes including Cd36, Fas, Acot2 and Slc27a1. In addition, PE suppressed gene expression of pro-inflammatory cytokines including Il-1α, Il-7, Il-11, Ifnα, Tnfα and Lepr in the hippocampi. Our findings support the protective effects of PE against high-fat diet-induced hepatic and neurological disease. Graphical Abstract
Impact of Patient-Clinical Team Secure Messaging on Communication Patterns and Patient Experience: Randomized Encouragement Design Trial

Background Although secure messaging (SM) between patients and clinical team members is a recommended component of continuous care, uptake by patients remains relatively low. We designed a multicomponent Supported Adoption Program (SAP) to increase SM adoption among patients using the Veterans Health Administration (VHA) for primary care. Objective Our goals were to (1) conduct a multisite, randomized, encouragement design trial to test the effectiveness of an SAP designed to increase patient engagement with SM through VHA’s online patient portal (My HealtheVet [MHV]) and (2) evaluate the impact of the SAP and patient-level SM adoption on perceived provider autonomy support and communication. Patient-reported barriers to SM adoption were also assessed. Methods We randomized 1195 patients at 3 VHA facilities who had MHV portal accounts but had never used SM. Half were randomized to receive the SAP, and half served as controls receiving usual care. The SAP consisted of encouragement to adopt SM via mailed educational materials, proactive SM sent to patients, and telephone-based motivational interviews. We examined differences in SM adoption rates between SAP recipients and controls at 9 months and 21 months. Follow-up telephone surveys were conducted to assess perceived provider autonomy support and self-report of telephone communication with clinical teams. Results Patients randomized to the SAP had significantly higher rates of SM adoption than the control group (101/595, 17.0% vs 40/600, 6.7%; P<.001). Most adopters in the SAP sent their first message without a motivational interview (71/101, 70.3%). The 10-percentage point difference in adoption persisted a full year after the encouragement ended (23.7%, 142/600 in the SAP group vs 13.5%, 80/595 in the control group, P<.001). We obtained follow-up survey data from 49.54% (592/1195) of the participants. SAP participants reported higher perceived provider autonomy support (5.7 vs 5.4, P=.007) and less telephone use to communicate with their provider (68.8% vs 76.0%, P=.05), compared to patients in the control group. Patient-reported barriers to SM adoption included self-efficacy (eg, not comfortable using a computer, 24%), no perceived need for SM (22%), and difficulties with portal password or login (17%). Conclusions The multicomponent SAP was successful in increasing use of SM 10 percentage points above standard care; new SM adopters reported improved perceptions of provider autonomy support and less use of the telephone to communicate with their providers. Still, despite the encouragement and technical assistance provided through the SAP, adoption rates were lower than anticipated, reaching only 24% at 21 months (10% above controls). Common barriers to adoption such as limited perceived need for SM may be more challenging to address and require different interventions than barriers related to patient self-efficacy or technical difficulties. Trial Registration ClinicalTrials.gov NCT02665468; https://clinicaltrials.gov/ct2/show/NCT02665468
An evaluation of the knowledge and attitudes of school staff related to diabetes care at school: The 10th year of the “diabetes program at school” in Turkey

The aim of this study was to measure the knowledge and attitudes of school staff regarding care in school for children with type 1 diabetes and to evaluate the contribution of the “Diabetes Program at School”(DPS). The data were collected through an online survey consisting of 55 questions, which included 39 knowledge and 16 attitude questions. The survey was delivered to the participating school staff via a link. A total of 55,677 people who completed 100% of the survey were included. Of the participants, 76% were teachers, 23% were school administrators and 0.1% were school nurses. 73% (40732) of the participants stated that they had heard about the “DPS”. Of the participants who were aware of the DPS 75%, 50%, and 41% stated an increase in their knowledge level, self‐confidence, and awareness respectively. Both scores were positively associated with being female and school nurse, having students with diabetes in the school, having been trained in childhood diabetes, being familiar with the program and being from the Western region of Turkey. The DPS is well known among school staff including teachers, school administrators, and school nurses. However, there are clear regional differences in the knowledge and attitude of school staff regarding diabetes care at school. Therefore, regional differences should be taken into account when planning the necessary interventions to prevent any further increase in the current inequalities. In addition, increasing the number of school nurses, together with strengthening the knowledge and attitude of school staff, can improve the level of diabetes care at school.
Angiopoietin‐like protein 4 promotes very‐low‐density lipoprotein assembly and secretion in bovine hepatocytes in vitro

In dairy cows, fatty liver is one of the most common metabolic diseases that occurs during the periparturient period. Angiopoietin‐like protein 4 (ANGPTL4) is a well‐known downstream target of peroxisome proliferator‐activated receptors (PPARs), which regulate the glucose and fatty acid metabolisms. The inhibition of lipoprotein lipase (LPL) activity interferes with the storage of triglycerides (TG) in adipocytes, which plays an essential role in lipid metabolism in rodents. However, it remains unclear whether ANGPTL4 is involved in the pathological process of fatty liver in dairy cows as a result of the regulation of the hepatocellular lipid transport system. This study intended to investigate the effect of ANGPTL4 on the very‐low‐density lipoprotein (VLDL) assembly and secretion in bovine hepatocytes. Bovine hepatocytes were isolated using a modified two‐step perfusion and collagenase digestion process, and treated with different concentrations of ANGPTL4 (0, 4, 12, and 24 ng/ml) for 24 hr. The results showed that a high concentration of ANGPTL4 could significantly increase the extracellular concentration of VLDL while reducing the intracellular content of TG. Thus, it was confirmed that ANGPTL4 could promote the transport of TG in the form of VLDL by partially regulating the expression of related proteins in hepatocytes, thereby contributing to the partial adaptive regulation of lipid transport in dairy cows.
Etanercept or Methotrexate Withdrawal in Rheumatoid Arthritis Patients in Sustained Remission

Patients with rheumatoid arthritis (RA) in whom remission is achieved following combination therapy with methotrexate plus etanercept face an ongoing medication burden. This study was undertaken to investigate whether sustained remission achieved on combination therapy can be maintained with either methotrexate or etanercept monotherapy, as assessed following discontinuation of one or the other medication from the combination.