Miracle-dz/UniFAR-FTUs huggingface dataset:
PARPs: All for One and One for All? Enhancing Diversity in Clinical Trials.

PARP inhibitors have revolutionized the management of ovarian cancer and are being licenced for other cancer indications. The clinical trials prompting licencing decisions in ovarian cancer were dominated by white participants or participant ethnicity was not documented. To compensate for this, replicative studies like L-MOCA can be run in specific ethnic groups. In future, strategies such as mandatory collection and publication of race and ethnicity data are essential alongside concerted efforts to widen the inclusivity of trial recruitment.
Analysis and design of compact wide bandpass filter with ultra-wide stopband using multi-stub loaded resonator

A compact microstrip multi-stub loaded bandpass filter (BPF) with ultra-wide stopband is introduced and investigated. Lumped-equivalent circuit (LEC) method is adopted to analyze the characteristics of the in-band response based upon the low frequency LEC and even-odd mode analytical method. Besides, equivalent transmission line circuit method with even-odd mode analytical method are adopted to discuss the mechanism of the out-band rejection based upon the transmission poles and the transmission zeros analysis of the even-/odd-mode equivalent circuits. Accordingly, the design and the optimization procedures of this type of filters are summarized. To experimentally validate the proposed method, the filter is fabricated and measured. The measured results illustrate this BPF centered at f 0 = 2.8 GHz, with −3 dB fractional bandwidth of 109.3%, the insert loss (IL) of less than 1 dB from 1.4 to 4 GHz, and the rejection level of 20 dB from 5.1 to 33.5 GHz (1.82f 0 to 11.96f 0 ).
Construction of a novel microRNA-based signature for predicting the prognosis of glioma

Abstract Background and purpose: Glioma is a frequent primary brain tumor. MicroRNAs (miRNA) have been shown to potentially play a crucial part in tumor development. Based on miRNAs and clinical factors, a model was constructed to predict the glioma prognosis. Methods: The miRNA expression profiles of glioma come from The Cancer Genome Atlas (TCGA, training group) and Chinese Glioma Genome Atlas (CGGA, validation group). Regression analyses of Cox and Lasso were applied to identity miRNAs associated with glioma prognosis in the TCGA database. The miRNAs were combined with clinical factors to construct individualized prognostic prediction models, whose performance was validated in the CGGA database. The role of miRNA in glioma development was investigated by in vitro experiments. Results: We identified five key miRNAs associated with glioma prognosis and constructed a prediction model. The area under ROC curve for predicting 3-year survival of glioma patients in the TCGA and CGGA groups was 0.844 and 0.770, respectively. The nomogram constructed using the miRNA risk scores and clinical factors showed high accuracy of prediction in the TCGA group (C-index of 0.820) and the CGGA group (C-index of 0.722). The miR-196b-5p altered the migration, proliferation, invasion, and apoptosis of glioma cells by regulating target genes, according to in vitro experiments. Conclusions: A miRNA-based individualized prognostic prediction model was constructed for glioma and miR-196b-5p was identified as a potential biomarker of glioma development.
Dietary Exposure to Bifenthrin and Fipronil Impacts Swimming Performance in Juvenile Chinook Salmon (Oncorhynchus tshawytscha)

Two commonly used insecticides, bifenthrin and fipronil, can accumulate in the prey of juvenile Chinook salmon, yet the effects of dietary exposure are not understood. Therefore, to better characterize the effect of a dietary exposure route, juvenile Chinook salmon were fed chironomids dosed with a concentration of 9 or 900 ng/g of bifenthrin, fipronil, or their mixture for 25 days at concentrations previously measured in field-collected samples. Chinook were assessed for maximum swimming performance (Umax) using a short-duration constant acceleration test and biochemical responses related to energetic processes (glucose levels) and liver health (aspartate aminotransferase (AST) activity). Chinook exposed to bifenthrin and bifenthrin and fipronil mixtures had a significantly reduced swimming performance, although not when exposed to fipronil alone. The AST activity was significantly increased in bifenthrin and mixture treatments and glucose levels were increased in Chinook following a mixture treatment, although not when exposed to fipronil alone. These findings suggest that there are different metabolic processes between bifenthrin and fipronil following dietary uptake that may influence toxicity. The significant reductions in swimming performance and increased levels of biochemical processes involved in energetics and fish heath could have implications for foraging activity and predator avoidance in wild fish at sensitive life stages.
Association of HbA1c with carotid artery plaques in patients with coronary heart disease: a retrospective clinical study

Abstract Background and aims Haemoglobin A1c (HbA1c) levels have been shown to be related to carotid artery plaques. However, studies on the relationship between HbA1c levels and carotid artery plaques in patients with coronary heart disease (CHD) are limited and inconsistent. Our objective was to examine the correlation between HbA1c levels and carotid artery plaques in patients with CHD. Methods The study comprised 9275 Chinese adults with CHD from January 1, 2014, to September 30, 2020. HbA1c levels were assessed, and colour Doppler ultrasound was used to evaluate the carotid artery, including plaque presence, intima-media thickness, and plaque echo properties, to investigate the association between HbA1c and carotid plaque. A logistic regression model was used to assess the association between carotid artery plaques, carotid plaque echogenicity, and HbA1c. Results The HbA1c level of the plaque-present group was higher than that of the plaque-absent group [6.1 (5.6–7.2) vs. 5.8 (5.5–6.5), p < 0.001]. In multiple linear regression analysis, intima-media thickness was associated with HbA1c (p < 0.001). Logistic regression showed that a higher HbA1c level was associated with plaque incidence as well as hyperechoic and heterogeneous plaques (p < 0.001). These associations persist after adjusting for age, sex, blood pressure, lipid profiles, alcohol consumption, and tobacco exposure. Conclusion HbA1c levels are notably associated with carotid artery plaque incidence, intima-media thickness, and plaque echogenicity in patients with CHD. These findings show that different levels of HbA1c may be an indicator for carotid artery plaques and thus, should be observed in patients with CHD. Graphical abstract
Multi-elemental analysis of colonial and post-colonial Nigerian coins by Proton Induced X-ray Emission (PIXE) spectrometry

The investigation of old and new coins from different countries in the world has generated a growing interest among numismatic and archaeological researchers. The challenge is to explain the large diversification of these coins, to determine the differences in composition, weight and physical aspects. A non-destructive physical method of ion beam analysis; PIXE was employed to investigate elemental properties of the coins. The weights of the coins varied between 1.89 and 11.46 g while their thicknesses were in the range of 0.10 to 0.40 mm. The elements; Al, Si, Mn, Fe and Zn were detected along with the major components of Ni and Cu. The elements displayed both positive and negative correlations. The study could aid in solving some scientifically questions of conservators and tourists on “what” material is it especially now that coins have long been demonetized in Nigeria.
Building Awareness of Diagnosis Together: Ambiguity During Progression-Free Survival Experienced by Patients With Lung Cancer and Caregivers in China

Background Lung cancer, as a multistep and multifactorial disease, is among the most fatal cancers worldwide. As new therapies are developed and early screening increases, patients tend to experience progression-free survival (PFS) as a coexistence of living and dying simultaneously. Objective The aim of this study was to explore the awareness context experienced by Chinese elderly patients and family members. Methods Interviews were conducted with 20 interviewees, including 13 elderly patients with lung cancer and 7 caregivers that were recruited using purposive sampling. Semistructured, face-to-face, in-depth interviews were conducted using a qualitative descriptive approach. Results Ambiguity was commonly experienced by patients with lung cancer with PFS. Three themes emerged from the data analysis: “ambiguity in cancer diagnosis,” “ambiguity in prognostic awareness,” and “ambiguity in identity. ” In this case, ambiguity refers to a situation or context in which patients are uncertain about whether there will be a recurrence of their cancer and when it might occur. Conclusions The findings highlighted that patients experienced ambiguity in response to unclear diagnoses, uncertain prognoses, and identity crises during PFS. Implications for Practice Healthcare teams should be equipped with psychosocial knowledge and communication skills to manage ambiguity in diagnosis and prognosis for patients with PFS.
Interleukin 17A rs2275913 polymorphism is associated with susceptibility to systemic lupus erythematosus: A meta and trial sequential analysis

Background The role of cytokines in the development of systemic lupus erythematosus (SLE) has received much attention. Interleukin-17 A upregulates several inflammation-related genes and is thought to have a crucial role in SLE development. The susceptibility to SLE development has been linked to functional genetic variations of the IL-17A gene; nevertheless, the findings have been conflicting. We conducted a meta-analysis that included previously published reports to establish a definitive conclusion on the role of the IL-17A rs2275913 polymorphism in SLE propensity. Materials and Methods The PubMed, Google Scholar, and Scopus databases were used to find eligible published articles. All analyses were conducted using Comprehensive Meta-analysis V3.1. Funnel plots and Egger’s regression analysis were used to assess publication bias. Q statistics and I2 test explored the heterogeneity among the included studies. Combined odds ratio, 95% confidence interval were calculated for each comparison model. Results Based on the inclusion and exclusion criteria, a total of four reports, comprising of 608 SLE patients and 815 healthy controls, were considered for the present meta-analysis. The homozygous comparison (AA vs. GG: combined odds ratio= 2.046, p = 0.005) and recessive genetic model (AA vs. GG+GA: combined odds ratio=1.901, p = 0.010) analysis revealed a significant association of rs2275913 with susceptibility to the development of SLE. However, other genetic comparisons (A vs. G, GA vs. GG, AA+GA vs. GG) failed to demonstrate such association. Furthermore, trial sequential analysis revealed a sufficient number of studies, including enough cases and controls that have already been considered to conclude the role of IL17-A rs2275913 polymorphism in SLE. Conclusions IL-17A rs2275913 polymorphism is associated with susceptibility to SLE development.
Advances in the Understanding of the Complex Role of Venous Sinus Stenosis in Idiopathic Intracranial Hypertension

Idiopathic intracranial hypertension (IIH) is a disorder characterized by elevated intracranial pressure (ICP) that predominantly affects young obese women. IIH is a diagnosis of exclusion. That is, if increased ICP is suspected, magnetic resonance imaging and magnetic resonance venography of the brain are recommended to exclude secondary causes. Imaging findings, such as empty sella, orbital findings, meningocele, and encephalocele, are not diagnostic of ICP, nor does their absence exclude ICP either. Therefore, venous manometry is recommended as the gold standard for evaluation, regardless of previous anatomic imaging results. Venous manometry is an invasive examination that is frequently applied to derive physiologic information concerning the nature of the pressure gradient. However, the pathogenesis of IIH has not been fully elucidated. The presence of venous sinus stenosis in a subset of patients has provided some support for the potential mechanisms underlying this condition. Hence, this review provides an up‐to‐date discussion on the potential pathogenic mechanisms of IIH with a special focus on venous sinus stenosis.
A two-step method to improve image quality of CBCT with phantom-based supervised and patient-based unsupervised learning strategies

Objective. In this study, we aimed to develop deep learning framework to improve cone-beam computed tomography (CBCT) image quality for adaptive radiation therapy (ART) applications. Approach. Paired CBCT and planning CT images of 2 pelvic phantoms and 91 patients (15 patients for testing) diagnosed with prostate cancer were included in this study. First, well-matched images of rigid phantoms were used to train a U-net, which is the supervised learning strategy to reduce serious artifacts. Second, the phantom-trained U-net generated intermediate CT images from the patient CBCT images. Finally, a cycle-consistent generative adversarial network (CycleGAN) was trained with intermediate CT images and deformed planning CT images, which is the unsupervised learning strategy to learn the style of the patient images for further improvement. When testing or applying the trained model on patient CBCT images, the intermediate CT images were generated from the original CBCT image by U-net, and then the synthetic CT images were generated by the generator of CycleGAN with intermediate CT images as input. The performance was compared with conventional methods (U-net/CycleGAN alone trained with patient images) on the test set. Results. The proposed two-step method effectively improved the CBCT image quality to the level of CT scans. It outperformed conventional methods for region-of-interest contouring and HU calibration, which are important to ART applications. Compared with the U-net alone, it maintained the structure of CBCT. Compared with CycleGAN alone, our method improved the accuracy of CT number and effectively reduced the artifacts, making it more helpful for identifying the clinical target volume. Significance. This novel two-step method improves CBCT image quality by combining phantom-based supervised and patient-based unsupervised learning strategies. It has immense potential to be integrated into the ART workflow to improve radiotherapy accuracy.
Cross-cultural adaptation and validation of a questionnaire on eating habits and physical activity of university students in confinement due to coronavirus disease

Abstract Objective: The purpose of the current study was to cross-culturally adapt and validate an online questionnaire to assess eating habits and physical activity of university students under confinement due to coronavirus disease (COVID-19). Design: Generation of a cross-sectional online survey to university students conducted during confinement due to COVID-19. The study was divided into two phases. Settings: Students, Chile. Participants: Phase 1 considered the process of translation and back translation, expert panel, cultural adaptation and the generation of a pilot to validate a preliminary format of the questionnaire. In Phase 2, information from the instrument was collected from two hundred and sixty-eight university students, ages 16 to 30 years old, with a mean age of 21·6 (3·3) The major proportion of participants were female (82 %). Results: The adapted questionnaire was statistically validated in three dimensions: (A) eating habits and behaviours during quarantine, (B) perception of risk and (C) physical activity changes during the quarantine. The reliability of Cronbach’s α for dimensions A, B and C was 0·59, 0·85 and 0·97, respectively. The complete questionnaire obtained 0·61 in internal consistency and 0·61 (0·58–0·67) ICC reliability. A statistically significant positive correlation matrix was observed. Conclusions: This questionnaire is a practical tool to obtain accurate information about the relation of COVID-19 confinement on people’s eating habits and physical activity. Therefore, it could contribute to establishing appropriate strategies to prevent negative effects on people’s health.
Pregnancy Outcomes: Effects of Metformin (POEM) study: a protocol for a long-term, multicentre, open-label, randomised controlled trial in gestational diabetes mellitus

Introduction Gestational diabetes mellitus (GDM) is a common disorder of pregnancy with health risks for mother and child during pregnancy, delivery and further lifetime, possibly leading to type 2 diabetes mellitus (T2DM). Current treatment is focused on reducing hyperglycaemia, by dietary and lifestyle intervention and, if glycaemic targets are not reached, insulin. Metformin is an oral blood glucose lowering drug and considered safe during pregnancy. It improves insulin sensitivity and has shown advantages, specifically regarding pregnancy-related outcomes and patient satisfaction, compared with insulin therapy. However, the role of metformin in addition to usual care is inconclusive and long-term outcome of metformin exposure in utero are lacking. The primary aim of this study is to investigate the early addition of metformin on pregnancy and long-term outcomes in GDM. Methods and analysis The Pregnancy Outcomes: Effects of Metformin study is a multicentre, open-label, randomised, controlled trial. Participants include women with GDM, between 16 and 32 weeks of gestation, who are randomised to either usual care or metformin added to usual care, with insulin rescue in both groups. Metformin is given up to 1 year after delivery. The study consists of three phases (A–C): A—until 6 weeks after delivery; B—until 1 year after delivery; C—observational study until 20 years after delivery. During phase A, the primary outcome is a composite score consisting of: (1) pregnancy-related hypertension, (2) large for gestational age neonate, (3) preterm delivery, (4) instrumental delivery, (5) caesarean delivery, (6) birth trauma, (7) neonatal hypoglycaemia, (8) neonatal intensive care admission. During phase B and C the primary outcome is the incidence of T2DM and (weight) development in mother and child. Ethics and dissemination The study was approved by the Central Committee on Research Involving Human Subjects in the Netherlands. Results will be submitted for publication in peer-reviewed journals. Trial registration number NCT02947503.
Osteoid osteoma mimicking refractory juvenile arthritis in a pediatric patient

A 9-year-old patient, complaining of pain and swelling of his left elbow for 3 months, was referred to the paediatric rheumatology consultation. On clinical exam-ination, there was a local swelling with limited joint mobility of the left elbow. The other joints were normal. There were no associated skin lesions, weight loss, or fever. His personal and family medical history were not relevant. A blood test for inflammatory markers, complete auto-immune serology, and Borrelia serology were all normal. the basis we suspected juvenile idiopathic arthritis and he was treated with local corticosteroid and oral non-steroidal anti-inflammatory drugs (NSAIDs). The patient was seen 1 with poor benefit from the infiltration. A new ultrasound was performed, which revealed an intra-articular effusion without a positive Doppler sig-nal, indicating inactivity of the rheumatological
The environmental requirements of piglets and use of the creep area

4 Sammendrag.5 List of papers.6 1.0. Introduction.7 1.1. General introduction.7 1.2. Important aspects of maternal behaviour in relation to piglet mortality.8 1.3. Piglet mortality.11 1.4. Thermoregulation in the neonatal piglet.14 1.5. Environmental preferences and piglet use of the creep area.17 2.0. The aim of the thesis.20 3.0. Methods.21 4.0. Results and general discussion.28 4.1. Results summary.28 4.2. Thermoregulatory behaviour and effects on space requirements . 28 4.3. Environmental preference in neonatal piglets.33 4.4. Piglet use of the creep area.35 4.5. Concluding remarks.40 4.6. Practical implications.41 4.7. Suggestions for further research.41 5.0. References.43 Acknowledgments.55 Papers І – V
FGF6 promotes cardiac repair after myocardial infarction by inhibiting the Hippo pathway

Myocardial infarction (MI) commonly occurs in patients with coronary artery disease and have high mortality. Current clinical strategies for MI still limited to reducing the death of myocardial cells but failed to replace these cells. This study aimed to investigate the role of fibroblast growth factor 6 (FGF6) in enhancing the proliferative potential of cardiomyocytes (CMs) after ischemic injury via the Hippo pathway.
Scalp HFO rates are higher for larger lesions

High‐frequency oscillations (HFO) in scalp EEG are a new and promising noninvasive epilepsy biomarker, providing added prognostic value, particularly in pediatric lesional epilepsy. However, it is unclear if lesion characteristics, such as lesion volume, depth, type, and localization, impact scalp HFO rates. We analyzed scalp EEG from 13 children and adolescents with focal epilepsy associated with focal cortical dysplasia (FCD), low‐grade tumors, or hippocampal sclerosis. We applied a validated automated detector to determine HFO rates in bipolar channels. We identified the lesion characteristics in MRI. Larger lesions defined by MRI volumetric analysis corresponded to higher cumulative scalp HFO rates (P = .01) that were detectable in a higher number of channels (P = .05). Both superficial and deep lesions generated HFO detectable in the scalp EEG. Lesion type (FCD vs tumor) and lobar localization (temporal vs extratemporal) did not affect scalp HFO rates in our study. Our observations support that all lesions may generate HFO detectable in scalp EEG, irrespective of their characteristics, whereas larger epileptogenic lesions generate higher scalp HFO rates over larger areas that are thus more accessible to detection. Our study provides crucial insight into scalp HFO detectability in pediatric lesional epilepsy, facilitating their implementation as an epilepsy biomarker in a clinical setting.
Identification of potential Staphylococcus aureus dihydrofolate reductase inhibitors using QSAR, molecular docking, dynamics simulations and free energy calculation

Abstract Herein we describe the use of molecular docking simulations, quantitative structure-activity relationships studies and ADMETox predictions to analyse the molecular recognition of a series of 7-aryl-2,4-diaminoquinazoline derivatives on the inhibition of Staphylococcus aureus dihydrofolate reductase and conducted a virtual screening to discover new potential inhibitors. A quantitative structure-activity relationship model was developed using 40 compounds and two selected descriptors. These descriptors indicated the importance of pKa and molar refractivity for the inhibitory activity against SaDHFR. The values of R2 train, CVLOO and R2 test generated by the model were 0.808, 0.766, and 0.785, respectively. The integration between QSAR, molecular docking, ADMETox analysis and molecular dynamics simulations with binding free energies calculation, yielded the compounds PC-124127620, PC-124127795 and PC-124127805 as promising candidates to SaDHFR inhibitors. These compounds presented high potency, good pharmacokinetics and toxicological profile. Thus, these molecules are good potential antimicrobial agent to treatment of infect disease caused by S. aureus. Communicated by Ramaswamy H. Sarma