Miracle-dz/UniFAR-FTUs huggingface dataset:
Histological and Somatic Mutational Profiles of Mismatch Repair Deficient Endometrial Tumours of Different Aetiologies

Simple Summary Endometrial cancers can arise due to an error in DNA mending known as mismatch repair. This can happen because of an error in the cancer itself (somatic) or due to an inherited error (Lynch syndrome). Treatment trials have considered endometrial cancers caused by either of these errors as identical. As it is easier to recruit people with Lynch syndrome, they may be overrepresented in this group despite being less numerous in clinical practice. This would not be an issue if somatic and Lynch syndrome-related endometrial cancers were similar at a molecular level. The data presented herein, however, indicates that these two routes to mismatch repair, although sharing many similarities, lead to endometrial cancers with distinct molecular and pathological features. This may explain the range of outcomes observed in clinical trials of endometrial cancers with mismatch repair errors. Abstract Background: Mismatch repair deficient (MMRd) tumours may arise from somatic events acquired during carcinogenesis or in the context of Lynch syndrome (LS), an inherited cancer predisposition condition caused by germline MMR pathogenic variants. Our aim was to explore whether sporadic and hereditary MMRd endometrial cancers (EC) display distinctive tumour biology. Methods: Clinically annotated LS-EC were collected. Histological slide review was performed centrally by two specialist gynaecological pathologists. Mutational analysis was by a bespoke 75- gene next-generation sequencing panel. Comparisons were made with sporadic MMRd EC. Multiple correspondence analysis was used to explore similarities and differences between the cohorts. Results: After exclusions, 135 LS-EC underwent independent histological review, and 64 underwent mutational analysis. Comparisons were made with 59 sporadic MMRd EC. Most tumours were of endometrioid histological subtype (92% LS-EC and 100% sporadic MMRd EC, respectively, p = NS). Sporadic MMRd tumours had significantly fewer tumour infiltrating lymphocytes (p ≤ 0.0001) and showed more squamous/mucinous differentiation than LS-EC (p = 0.04/p = 0.05). PTEN mutations were found in 88% sporadic MMRd and 61% LS-EC, respectively (p < 0.001). Sporadic MMRd tumours had significantly more mutations in PDGFRA, ALK, IDH1, CARD11, CIC, MED12, CCND1, PTPN11, RB1 and KRAS, while LS-EC showed more mutations affecting SMAD4 and ARAF. LS-EC showed a propensity for TGF-β signalling disruption. Cluster analysis found that wild type PTEN associates predominantly with LS-EC, whilst co-occurring mutations in PTEN, PIK3CA and KRAS predict sporadic MMRd EC. Conclusions: Whilst MMRd EC of hereditary and sporadic aetiology may be difficult to distinguish by histology alone, differences in infiltrating immune cell counts and mutational profile may predict heterogenous responses to novel targeted therapies and warrant further study.
Metabolic Health, Obesity, and Renal Function: 2013–2018 National Health and Nutrition Examination Surveys

Rising rates of metabolic syndrome, obesity, and mortality from chronic kidney disease (CKD) have prompted further investigation into the association between metabolic phenotypes and CKD. Purpose: To report the frequency of strictly defined metabolic phenotypes, renal function within each phenotype, and individual risk factors associated with reduced renal function. We utilized the 2013–2018 National Health and Nutrition Examination Surveys (NHANES) and complex survey sample weighting techniques to represent 220 million non-institutionalized U.S. civilians. Metabolic health was defined as having zero of the risk factors defined by the National Cholesterol Education Program with the exception of obesity, which was defined as BMI ≥ 30 kg/m2 in non-Asians and BMI ≥ 25 kg/m2 in Asians. The metabolically healthy normal (MUN) phenotype comprised the highest proportion of the population (38.40%), whereas the metabolically healthy obese (MHO) was the smallest (5.59%). Compared to the MHN reference group, renal function was lowest in the strictly defined MUN (B = −9.60, p < 0.001) and highest in the MHO (B = 2.50, p > 0.05), and this persisted when an increased number of risk factors were used to define metabolic syndrome. Systolic blood pressure had the strongest correlation with overall eGFR (r = −0.25, p < 0.001), and individuals with low HDL had higher renal function compared to the overall sample. The MUN phenotype had the greatest association with poor renal function. While the MHO had higher renal function, this may be due to a transient state caused by renal hyperfiltration. Further research should be done to investigate the association between dyslipidemia and CKD.
A Comprehensive Review on Radiomics and Deep Learning for Nasopharyngeal Carcinoma Imaging

Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumours of the head and neck, and improving the efficiency of its diagnosis and treatment strategies is an important goal. With the development of the combination of artificial intelligence (AI) technology and medical imaging in recent years, an increasing number of studies have been conducted on image analysis of NPC using AI tools, especially radiomics and artificial neural network methods. In this review, we present a comprehensive overview of NPC imaging research based on radiomics and deep learning. These studies depict a promising prospect for the diagnosis and treatment of NPC. The deficiencies of the current studies and the potential of radiomics and deep learning for NPC imaging are discussed. We conclude that future research should establish a large-scale labelled dataset of NPC images and that studies focused on screening for NPC using AI are necessary.
Potential Relationship between the Changes in Circulating microRNAs and the Improvement in Glycaemic Control Induced by Grape Pomace Supplementation

MicroRNAs (miRNAs) represent important tools in medicine and nutrition as new biomarkers, and can act as mediators of nutritional and pharmacological interventions. The aim of the present study was to analyse the effect of grape pomace supplementation on the expression of seven selected miRNAs and their potential relationship with the observed positive effect on glycaemic control, in order to shed light on the mechanism underlying the beneficial effect of this dietary intervention. For this purpose, plasma samples were obtained from 49 subjects with metabolic syndrome. After supplementation with grape pomace (6 weeks), these subjects were categorised as responders (n = 23) or non-responders (n = 26) according to the changes in their fasting insulin rate. MiRNA expression at baseline and at the end of the supplementation was analysed by RT-PCR, and the MiRecords Database was used to identify potential target genes for the studied miRNAs. The increase observed in miR-23a in the whole cohort was present in both subgroups of participants. The increase in miR-181a was significant among non-responders but not responders. The decrease in miR-30c and miR-222 was found in the responders, but not in the non-responders. No changes were observed in miR-10a, miR-151a, miR-181a, and miR-let-7a expressions. After analysing these results, a potential involvement of the reduced expression of miR-30c and miR-222, two microRNAs associated with insulin resistance and diabetes, in the improvement of glycaemic control produced by grape pomace administration, can be proposed. Further research is needed to confirm the involvement of glycolytic enzymes, PI3K, AMPK, and IRS-1 in the effect of grape pomace, as suggested by the changes induced in microRNAs.
Use and Significance of Nursing Diagnosis in Hospital Emergencies: A Phenomenological Approach

Background: Professional nursing organizations recommend the use of nursing diagnosis to enhance and facilitate the standardization of care and the development of a common language used by nursing practitioners. In the clinical reality of hospital emergency departments, however, its use is controversial. The objectives of the research are (a) to explore the use of nursing diagnosis in hospital emergency departments, and (b) to describe the meaning of nursing diagnosis for hospital emergency nurses. Methods: A qualitative phenomenological study was conducted. A purposeful sampling and snowball technique were used. Data were collected using in-depth interviews, researchers’ field notes, and documental analysis. An inductive analysis based on Giorgi´s proposal was used to identify significant emerging themes from interviews and field notes. Seventeen participants with a mean age of 40 were recruited. Results: Three themes were identified. The results showed how the use of nursing diagnosis in hospital emergency departments depends on nurses to apply a working methodology in their practice, along with other dimensions such as the characteristics of emergency care, the type of health problems, and the complexity of care. Conclusions: The use of standardized language in emergency departments is complex due to the overcrowded nature of care in these settings.
Proof of Concept Novel Configurable Chipless RFID Strain Sensor

This paper contains two main areas of research: First, this work outlines a novel, highly sensitive strain sensor design that should support various levels of deformation, depending on the substrate type used. Physical implementations in this work have focused on proving its large deformation capabilities, and simulations have been used to assess its more general electromagnetic response. The other part of this paper focusses on exploring other effects that will impact the sensing of strain of resolutions below 10 με, which is a capability achieved by other aerospace-grade strain sensor technologies. These effects are limited to mechanical swelling and sensor orientation in the azimuth and elevation planes, as these appear to be unexplored and highly relevant issues to the topic of chipless RFID-based strain sensing. From this exploration, it is apparent that the effects of mechanical swelling and sensor orientation (amongst others) will need to be addressed in any real-life implementation of the sensor, requiring a strain resolution below 10 με.
Water Dynamics in Whey-Protein-Based Composite Hydrogels by Means of NMR Relaxometry

Whey-protein-isolate-based composite hydrogels with encapsulated black carrot (Daucus carota) extract were prepared by heat-induced gelation. The hydrogels were blended with gum tragacanth, pectin and xanthan gum polysaccharides for modulating their properties. 1H spin-lattice relaxation experiments were performed in a broad frequency range, from 4 kHz to 30 MHz, to obtain insight into the influence of the different polysaccharides and of the presence of black carrot on dynamical properties of water molecules in the hydrogel network. The 1H spin-lattice relaxation data were decomposed into relaxation contributions associated with confined and free water fractions. The population of the confined water fraction and the value of the translation diffusion coefficient of water molecules in the vicinity of the macromolecular network were quantitatively determined on the basis of the relaxation data. Moreover, it was demonstrated that the translation diffusion is highly anisotropic (two-dimensional, 2D).
Sex-Dependent Effects of Intestinal Microbiome Manipulation in a Mouse Model of Alzheimer’s Disease

Mechanisms linking intestinal bacteria and neurodegenerative diseases such as Alzheimer’s disease (AD) are still unclear. We hypothesized that intestinal dysbiosis might potentiate AD, and manipulating the microbiome to promote intestinal eubiosis and immune homeostasis may improve AD-related brain changes. This study assessed sex differences in the effects of oral probiotic, antibiotics, and synbiotic treatments in the AppNL-G-F mouse model of AD. The fecal microbiome demonstrated significant correlations between bacterial genera in AppNL-G-F mice and Aβ plaque load, gliosis, and memory performance. Female and not male AppNL-G-F mice fed probiotic but not synbiotic exhibited a decrease in Aβ plaques, microgliosis, brain TNF-α, and memory improvement compared to no treatment controls. Although antibiotics treatment did not produce these multiple changes in brain cytokines, memory, or gliosis, it did decrease Aβ plaque load and colon cytokines in AppNL-G-F males. The intestinal cytokine milieu and splenocyte phenotype of female but not male AppNL-G-F mice indicated a modest proinflammatory innate response following probiotic treatment compared to controls, with an adaptive response following antibiotics treatment in male AppNL-G-F mice. Overall, these results demonstrate the beneficial effects of probiotic only in AppNL-G-F females, with minimal benefits of antibiotics or synbiotic feeding in male or female mice.
Magnetic Resonance Imaging for Surveillance of Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis

Our meta-analysis aimed to evaluate the diagnostic performance of surveillance magnetic resonance imaging (sMRI) for detecting hepatocellular carcinoma (HCC), and to compare the diagnostic performance of sMRI between different protocols. Original articles about the diagnostic accuracy of sMRI for detecting HCC were found in major databases. The meta-analytic pooled sensitivity and specificity of sMRI for detecting HCC were determined using a bivariate random effects model. The pooled sensitivity and specificity of full MRI and abbreviated MRI protocols were compared using bivariate meta-regression. In the total seven included studies (1830 patients), the pooled sensitivity of sMRI for any-stage HCC and very early-stage HCC were 85% (95% confidence interval, 79–90%; I2 = 0%) and 77% (66–85%; I2 = 32%), respectively. The pooled specificity for any-stage HCC and very early-stage HCC were 94% (90–97%; I2 = 94%) and 94% (88–97%; I2 = 96%), respectively. The pooled sensitivity and specificity of abbreviated MRI protocols were 87% (80–94%) and 94% (90–98%), values that were comparable with those of full MRI protocols (84% [76–91%] and 94% [89–99%]; p = 0.83). In conclusion, sMRI had good sensitivity for detecting HCC, particularly very early-stage HCC. Abbreviated MRI protocols for HCC surveillance had comparable diagnostic performance to full MRI protocols.
Synthetic Olfactory Agonist Use in the Farrowing House to Reduce Sow Distress and Improve Piglet Survival

Simple Summary Within intensive livestock industries, it is important to pursue the continual improvement of animal welfare. The farrowing crate design in most piggeries is currently the best way to optimize piglet welfare and reduce piglet mortality caused by being crushed by the sow. However, some studies have shown that restriction in a farrowing crate exacerbates sow distress at specific times during farrowing at lactation, which may compromise piglet survival. Therefore, there is a need to investigate strategies that may alleviate the stress experienced by the sow due to being confined. A synthetic olfactory agonist, a commercial product that mimics naturally occurring pheromones, previously reduced aggressive interactions in sows. Therefore, this product was investigated to determine its effectiveness at reducing sow stress and improving piglet survival during birth and lactation. We found no effect on the sow’s stress hormone levels between treatments in response to a stressor. However, first-litter sows experienced a decreased farrowing duration, but this did not extend to improvements in piglet pre-weaning survival. This synthetic olfactory agonist does not appear to be a suitable tool to reduce sow distress around birth or improve piglet pre-weaning survival. Abstract The aim of the study was to investigate if the application of a synthetic olfactory agonist (SOA) would reduce indicators of stress in sows, in response to a stressor prior to parturition, and if it would improve farrowing house performance of sows and their piglets. Two studies were conducted: an intensive study with 47 sows, either having their first or second litter (Control n = 24; SOA n = 23); and a commercial validation study with 418 sows, either having their first litter or have had multiple litters (Control n = 210; SOA n = 208). Within the intensive study, sows were housed with or without a synthetic olfactory agonist suspended in the creep area of the farrowing crate, whereas within the commercial validation study, sows were housed with or without a synthetic olfactory agonist suspended over the adjoining creep area of two farrowing crates. Within the intensive study, despite a discernible increase in cortisol concentration in response to a stressor (snout rope test), cortisol response was not different between treatments (p > 0.05). Farrowing duration in first-litter sows exposed to the SOA was decreased (p < 0.001) whilst there was no impact on farrowing duration in second litter sows. Piglets were not attracted by the SOA to increase their utilisation of the creep area and spent more time in proximity to the sow (p < 0.05). Within the commercial validation study, no impacts were seen on piglet production measures (p > 0.05). Largely the use of an SOA within the farrowing house did not impact the sow or her piglets in either the intensive study or commercial validation study. Based on these current results, the use of SOA within the farrowing house is not supported.
Dynamin Inhibitors Prevent the Establishment of the Cytomegalovirus Assembly Compartment in the Early Phase of Infection

Cytomegalovirus (CMV) infection initiates massive rearrangement of cytoplasmic organelles to generate assembly compartment (AC). The earliest events, the establishment of the preAC, are initiated in the early phase as an extensive reorganization of early endosomes (EEs), endosomal recycling compartment (ERC), trans-Golgi network (TGN), and the Golgi. Here, we demonstrate that dynamin inhibitors (Dynasore, Dyngo-4a, MiTMAB, and Dynole-34-2) block the establishment of the preAC in murine CMV (MCMV) infected cells. In this study, we extensively analyzed the effect of Dynasore on the Golgi reorganization sequence into the outer preAC. We also monitored the development of the inner preAC using a set of markers that define EEs (Rab5, Vps34, EEA1, and Hrs), the EE-ERC interface (Rab10), the ERC (Rab11, Arf6), three layers of the Golgi (GRASP65, GM130, Golgin97), and late endosomes (Lamp1). Dynasore inhibited the pericentriolar accumulation of all markers that display EE-ERC-TGN interface in the inner preAC and prevented Golgi unlinking and dislocation to the outer preAC. Furthermore, in pulse-chase experiments, we demonstrated that the presence of dynasore only during the early phase of MCMV infection (4–14 hpi) is sufficient to prevent not only AC formation but also the synthesis of late-phase proteins and virion production. Therefore, our results indicate that dynamin-2 acts as a part of the machinery required for AC generation and rearrangement of EE/ERC/Golgi membranes in the early phase of CMV infection.
Growth Suppression of a Gingivitis and Skin Pathogen Cutibacterium (Propionibacterium) acnes by Medicinal Plant Extracts

Propionibacterium acnes, newly reclassified as Cutibacterium acnes, is an anaerobic Gram-positive bacterium causing acne, found mainly on the skin. In addition, P. acnes is responsible for inflammation of the gums (gingivitis) and blood vessels, consequently leading to various diseases in the human body. In recent years, the evolution of microorganisms, such as P. acnes, that have become resistant to many commercial antibiotics due to the widespread use of antimicrobial drugs in the treatment of infectious diseases has emerged as a major clinical problem. We here analyzed the potential use of 37 medicinal plant extracts as plausible candidates for treating P. acnes, in terms of total phenolic and flavonoid contents, antioxidants scavenging and antimicrobial activity. Consequently, methanol extracts from 14 medicinal plants showed promising antimicrobial activities against P. acnes. In particular, as the extracts from Chrysosplenium flagelliferum F. and Thuja orientalis L. exhibited distinct antimicrobial activities in both the broth dilution and disc diffusion assay, they could be effectively used as active ingredients for preventing or treating inflammatory periodontal diseases, such as periodontitis.
Coevolved Multidrug-Resistant HIV-1 Protease and Reverse Transcriptase Influences Integrase Drug Susceptibility and Replication Fitness

Integrase strand transfer inhibitors (InSTIs) are recommended agents in first-line combination antiretroviral therapy (cART). We examined the evolution of drug resistance mutations throughout HIV-1 pol and the effects on InSTI susceptibility and viral fitness. We performed single-genome sequencing of full-length HIV-1 pol in a highly treatment-experienced patient, and determined drug susceptibility of patient-derived HIV-1 genomes using a phenotypic assay encompassing full-length pol gene. We show the genetic linkage of multiple InSTI-resistant haplotypes containing major resistance mutations at Y143, Q148 and N155 to protease inhibitor (PI) and reverse transcriptase inhibitor (RTI) resistance mutations. Phenotypic analysis of viruses expressing patient-derived IN genes with eight different InSTI-resistant haplotypes alone or in combination with coevolved protease (PR) and RT genes exhibited similar levels of InSTI susceptibility, except for three haplotypes that showed up to 3-fold increases in InSTI susceptibility (p ≤ 0.032). The replicative fitness of most viruses expressing patient-derived IN only significantly decreased, ranging from 8% to 56% (p ≤ 0.01). Interestingly, the addition of coevolved PR + RT significantly increased the replicative fitness of some haplotypes by up to 73% (p ≤ 0.024). Coevolved PR + RT contributes to the susceptibility and viral fitness of patient-derived IN viruses. Maintaining patients on failing cART promotes the selection of fitter resistant strains, and thereby limits future therapy options.
Acute Coronary Syndrome in the Older Patient

Coronary artery disease is one of the leading causes of morbidity and mortality, and its prevalence increases with age. The growing number of older patients and their differential characteristics make its management a challenge in clinical practice. The aim of this review is to summarize the state-of-the-art in diagnosis and treatment of acute coronary syndromes in this subgroup of patients. This comprises peculiarities of ST-segment elevation myocardial infarction (STEMI) management, updated evidence of non-STEMI therapeutic strategies, individualization of antiplatelet treatment (weighting ischemic and hemorrhagic risks), as well as assessment of geriatric conditions and ethical issues in decision making.
Neural-Network Based Modeling of I/O Buffer Predriver under Power/Ground Supply Voltage Variations

This paper presents a neural-network based nonlinear behavioral modelling of I/O buffer that accounts for timing distortion introduced by nonlinear switching behavior of the predriver electrical circuit under power and ground supply voltage (PGSV) variations. Model structure and I/O device characterization along with extraction procedure were described. The last stage of the I/O buffer is modelled as nonlinear current-voltage (I-V) and capacitance voltage (C-V) functions capturing the nonlinear dynamic impedances of the pull-up and pull-down transistors. The mathematical model structure of the predriver was derived from the analysis of the large-signal electrical circuit switching behavior. Accordingly, a generic and surrogate multilayer neural network (NN) structure was considered in this work. Timing series data which reflects the nonlinear switching behavior of the multistage predriver’s circuit PGSV variations, were used to train the NN model. The proposed model was implemented in the time-domain solver and validated against the reference transistor level (TL) model and the state-of-the-art input-output buffer information specification (IBIS) behavioral model under different scenarios. The analysis of jitter was performed using the eye diagrams plotted at different metrics values.