Miracle-dz/UniFAR-FTUs huggingface dataset:
Immune profiling and immunotherapeutic targets in pancreatic cancer

Background Immunotherapeutic approaches for pancreatic ductal adenocarcinoma (PDAC) are less successful as compared to many other tumor types. In this study, comprehensive immune profiling was performed in order to identify novel, potentially actionable targets for immunotherapy. Methods Formalin-fixed paraffin embedded (FFPE) specimens from 68 patients were evaluated for expression of 395 immune-related markers (RNA-seq), mutational burden by complete exon sequencing of 409 genes, PD-L1 expression by immunohistochemistry (IHC), pattern of tumor infiltrating lymphocytes (TILs) infiltration by CD8 IHC, and PD-L1/L2 copy number by fluorescent in situ hybridization (FISH). Results The seven classes of actionable genes capturing myeloid immunosuppression, metabolic immunosuppression, alternative checkpoint blockade, CTLA-4 immune checkpoint, immune infiltrate, and programmed cell death 1 (PD-1) axis immune checkpoint, discerned 5 unique clinically relevant immunosuppression expression profiles (from most to least common): (I) combined myeloid and metabolic immunosuppression [affecting 25 of 68 patients (36.8%)], (II) multiple immunosuppressive mechanisms (29.4%), (III) PD-L1 positive (20.6%), (IV) highly inflamed PD-L1 negative (10.3%); and (V) immune desert (2.9%). The Wilcoxon rank-sum test was used to compare the PDAC cohort with a comparison cohort (n=1,416 patients) for the mean expressions of the 409 genes evaluated. Multiple genes including TIM3, VISTA, CCL2, CCR2, TGFB1, CD73, and CD39 had significantly higher mean expression versus the comparison cohort, while three genes (LAG3, GITR, CD38) had significantly lower mean expression. Conclusions This study demonstrates that a clinically relevant unique profile of immune markers can be identified in PDAC and be used as a roadmap for personalized immunotherapeutic decision-making strategies.
Doppelganger-based training: Imitating our virtual self to accelerate interpersonal skills learning

Interpersonal skills require mastering a wide range of competencies such as communication and adaptation to different situations. Effective training includes the use of videos in which role models perform the desired behaviours such that trainees can learn through behavioural mimicry. However, new technologies allow new ways of designing training. In the present study, given that virtual reality is emerging as a valuable training setting, we compare two different demonstration conditions within virtual reality by investigating the extent to which the use of doppelgangers as role models can boost trainees’ interpersonal skills development as compared to a role model that does not resemble the trainees. We also assess trainees’ level of self-efficacy and gender as potential moderators in this relationship. Participants delivered a speech in front of a virtual audience twice. Before delivering their second speech, they watched a role model giving a speech in front of the same audience. The role model was either their doppelganger or an avatar of the same gender depending on the condition they were randomly assigned to. Results showed that the doppelganger-based training was the most beneficial for male trainees low in self-efficacy. These findings have important implications for training design, suggesting that doppelganger-based training might be effective only for a specific subset of trainees.
The Ratio of RAC1B to RAC1 Expression in Breast Cancer Cell Lines as a Determinant of Epithelial/Mesenchymal Differentiation and Migratory Potential

Breast cancer (BC) is a heterogenous disease encompassing tumors with different histomorphological phenotypes and transcriptionally defined subtypes. However, the non-mutational/epigenetic alterations that are associated with or causally involved in phenotype diversity or conversion remain to be elucidated. Data from the pancreatic cancer model have shown that the small GTPase RAC1 and its alternatively spliced isoform, RAC1B, antagonistically control epithelial–mesenchymal transition and cell motility induced by transforming growth factor β. Using a battery of established BC cell lines with either a well-differentiated epithelial or poorly differentiated mesenchymal phenotype, we observed subtype-specific protein expression of RAC1B and RAC1. While epithelial BC lines were RAC1Bhigh and RAC1low, mesenchymal lines exhibited the reverse expression pattern. High RAC1B and/or low RAC1 abundance also correlated closely with a poor invasion potential, and vice versa, as revealed by measuring random cell migration (chemokinesis), the preferred mode of cellular movement in cells that have undergone mesenchymal transdifferentiation. We propose that a high RAC1B:RAC1 ratio in BC cells is predictive of an epithelial phenotype, while low RAC1B along with high RAC1 is a distinguishing feature of the mesenchymal state. The combined quantitative assessment of RAC1B and RAC1 in tumor biopsies of BC patients may represent a novel diagnostic tool for probing molecular subtype and eventually predict malignant potential of breast tumors.
Autofluorescence Imaging of the Skin Is an Objective Non-Invasive Technique for Diagnosing Pseudoxanthoma Elasticum

Pseudoxanthoma elasticum (PXE) is a rare multisystemic autosomal recessive connective tissue disease. In most cases, skin manifestations of PXE are the first to develop, followed later by severe ocular and cardiovascular complications. In our present study, in addition to dermoscopy, we introduced novel techniques, autofluorescence (AF) and diffuse reflectance (DR) imaging for the assessment of affected skin sites of five PXE patients. PXE-affected skin areas in most skin sites showed a previously observed pattern upon dermoscopic examination. With the novel imaging, PXE-affected skin lesions displayed high AF intensity. During our measurements, significantly higher mean, minimum and maximum AF intensity values were found in areas of PXE-affected skin when compared to uninvolved skin. Conversely, images acquired with the use of 660 and 940 nm illumination showed no mentionable difference. Our results demonstrate that AF imaging may be used in the in vivo diagnostics and quantification of the severity of the skin lesions of PXE patients. In addition, it is a safe, fast and cost-effective diagnostic method. AF imaging may be also used to objectively monitor the efficacy of the possible novel therapeutic approaches of PXE in the future.
Enthalpy of formation of the cubic fluorite phase in the ceria–zirconia system

The enthalpy of formation of cubic ceria–zirconia solid solutions ( c -Ce_(1−_ x _)Zr_ x O_2, 0.05 ⩽ x ⩽ 0.75) at 25 °C with respect to monoclinic zirconia ( m -ZrO_2) and cubic ceria ( c -CeO_2) has been measured by high-temperature oxide melt solution calorimetry. In contrast to fluorite solid solutions containing trivalent oxides (e.g., yttria–zirconia), mixing in c -Ce_1−_ x Zr_ x O_2 shows moderate positive deviation from ideality. Evaluating the data within the framework of a regular solution model, the interaction parameter, Ω, is +51.0 ± 8.0 kJ/mol. The introduction of undersized Zr into CeO_2 severely distorts and destabilizes the oxygen sublattice. Destabilization of c -Ce_1−_ x Zr_ x O_2 may be relieved by reduction or clustering. A stable ordered compound in the CeO_2–ZrO_2 system is thermodynamically unlikely.
Role of Rho-GTPases in megakaryopoiesis

ABSTRACT Megakaryocytes (MKs) are the bone marrow (BM) cells that generate blood platelets by a process that requires: i) polyploidization responsible for the increased MK size and ii) cytoplasmic organization leading to extension of long pseudopods, called proplatelets, through the endothelial barrier to allow platelet release into blood. Low level of localized RHOA activation prevents actomyosin accumulation at the cleavage furrow and participates in MK polyploidization. In the platelet production, RHOA and CDC42 play opposite, but complementary roles. RHOA inhibits both proplatelet formation and MK exit from BM, whereas CDC42 drives the development of the demarcation membranes and MK migration in BM. Moreover, the RhoA or Cdc42 MK specific knock-out in mice and the genetic alterations in their down-stream effectors in human induce a thrombocytopenia demonstrating their key roles in platelet production. A better knowledge of Rho-GTPase signalling is thus necessary to develop therapies for diseases associated with platelet production defects. Abbreviations: AKT: Protein Kinase BARHGEF2: Rho/Rac Guanine Nucleotide Exchange Factor 2ARP2/3: Actin related protein 2/3BM: Bone marrowCDC42: Cell division control protein 42 homologCFU-MK: Colony-forming-unit megakaryocyteCIP4: Cdc42-interacting protein 4mDIA: DiaphanousDIAPH1; Protein diaphanous homolog 1ECT2: Epithelial Cell Transforming Sequence 2FLNA: Filamin AGAP: GTPase-activating proteins or GTPase-accelerating proteinsGDI: GDP Dissociation InhibitorGEF: Guanine nucleotide exchange factorHDAC: Histone deacetylaseLIMK: LIM KinaseMAL: Megakaryoblastic leukaemiaMARCKS: Myristoylated alanine-rich C-kinase substrateMKL: Megakaryoblastic leukaemiaMLC: Myosin light chainMRTF: Myocardin Related Transcription FactorOTT: One-Twenty Two ProteinPACSIN2: Protein Kinase C And Casein Kinase Substrate In Neurons 2PAK: P21-Activated KinasePDK: Pyruvate Dehydrogenase kinasePI3K: Phosphoinositide 3-kinasePKC: Protein kinase CPTPRJ: Protein tyrosine phosphatase receptor type JRAC: Ras-related C3 botulinum toxin substrate 1RBM15: RNA Binding Motif Protein 15RHO: Ras homologousROCK: Rho-associated protein kinaseSCAR: Suppressor of cAMP receptorSRF: Serum response factorSRC: SarcTAZ: Transcriptional coactivator with PDZ motifTUBB1: Tubulin β1VEGF: Vascular endothelial growth factorWAS: Wiskott Aldrich syndromeWASP: Wiskott Aldrich syndrome proteinWAVE: WASP-family verprolin-homologous proteinWIP: WASP-interacting proteinYAP: Yes-associated protein
How to learn skilled communication in primary care MUS consultations: a focus group study

Abstract Background Many general practitioners (GPs) experience communication problems in medically unexplained symptoms (MUS) consultations as they are insufficiently equipped with adequate communication skills or do not apply these in MUS consultations. Objective To define the most important learnable communication elements during MUS consultations according to MUS patients, GPs, MUS experts and teachers and to explore how these elements should be taught to GPs and GP trainees. Methods Five focus groups were conducted with homogeneous groups of MUS patients, GPs, MUS experts and teachers. MUS patients and GPs formulated a list of important communication elements. MUS experts identified from this list the most important communication elements. Teachers explored how these elements could be trained to GPs and GP trainees. Two researchers independently analysed the data applying the principles of constant comparative analysis. Results MUS patients and GPs identified a list of important communication elements. From this list, MUS experts selected five important communication elements: (1) thorough somatic and psychosocial exploration, (2) communication with empathy, (3) creating a shared understanding of the problem, (4) providing a tangible explanation and (5) taking control. Teachers described three teaching methods for these communication elements: (1) awareness and reflection of GPs about their feelings towards MUS patients, (2) assessment of GPs’ individual needs and (3) training and supervision in daily practice. Conclusion Teachers consider a focus on personal attitudes and needs, which should be guided by opportunities to practice and receive supervision, as the best method to teach GPs about communication in MUS consultations. KEY POINTS Many GPs experience difficulties in communication with patients with MUS. There is a need to equip GPs with communication skills to manage MUS consultations more adequately. Role-playing with simulation patients, reflection on video-consultations and joint consultations with the supervisor may increase the GPs’ awareness of their attitude towards MUS patients and may help GPs to identify their individual learning-points.
Insulin gene enhancer protein 1 mediates glycolysis and tumorigenesis of gastric cancer through regulating glucose transporter 4

Insulin gene enhancer protein 1, (ISL1), a LIM‐homeodomain transcription factor, is involved in multiple tumors and is associated with insulin secretion and metabolic phenotypes. However, the role of ISL1 in stimulating glycolysis to promote tumorigenesis in gastric cancer (GC) is unclear. In this study, we aimed to characterize the expression pattern of ISL1 in GC patients and explore its molecular biological mechanism in glycolysis and tumorigenesis.
Association of Performance Status With Survival in Patients With Advanced Non–Small Cell Lung Cancer Treated With Pembrolizumab Monotherapy

Key Points Question Is Eastern Cooperative Oncology Group (ECOG) performance status at the beginning of therapy associated with survival outcomes in patients with advanced non–small cell lung cancer who are treated with palliative pembrolizumab monotherapy? Findings In this cohort study of 74 patients, those with ECOG performance status of at least 2 had significantly lower disease control, progression-free survival, and overall survival than those with performance status of 0 or 1. Survival differences remained significant after multivariable adjustment for confounding factors. Meaning These findings suggest that ECOG performance status should be considered while making shared therapeutic decisions regarding pembrolizumab monotherapy with patients.
Enhanced N170 to outgroup faces: Perceptual novelty or prejudice?

ABSTRACT Habituation to ethnic ingroup members has been reported to be greater than to ethnic outgroup members. This pattern could be due to the lack of perceptive experience (familiarity) with outgroup facial morphs or, alternatively, to the prejudice held toward that outgroup. We explored this disjunctive in 71 participants, all Spanish, who were experimentally habituated to faces from their Ingroup and to faces from two unfamiliar outgroups, one for which there is low probability of prejudice in this population (Non-prejudiced Outgroup), and one for which the probability of prejudice is higher (Prejudiced Outgroup). We indexed habituation through event-related potentials, concretely as the differential amplitude of the face-sensitive N170 component from Initial to Final trials of each group. Afterward, participants completed several prejudice measures. N170 showed significant habituation to all faces, though it did not differ among groups. However, a regression analysis revealed that individual habituation to the Outgroup faces was inversely related to implicit prejudice scores. Importantly, N170 amplitudes were maximal for the Prejudiced Outgroup in both Initial and Final trials. We conclude that these effects are explained by the prejudice held toward a specific outgroup rather than perceptive experience.
Type 2 diabetes and heart failure: insights from the global DISCOVER study

Heart failure (HF) is increasingly recognized as a major cause of morbidity and mortality in patients with type 2 diabetes (T2D), but the global epidemiology and treatment of HF in T2D are not well defined. This study aimed to examine the global prevalence of HF and the incidence of HF over 3 years of follow‐up in patients with T2D [by presence and absence of co‐existing coronary artery disease (CAD)].
Chemical composition and synergistic effect of three Moroccan lavender EOs with ciprofloxacin against foodborne bacteria: a promising approach to modulate antimicrobial resistance

The aim of this study was to determine the chemical profile of the essential oils (EOs) of three Moroccan lavender species (Lavandula pedunculata, LP; Lavandula angustifolia, LA; and Lavandula maroccana, LM) and to investigate, for the first time, the synergistic effect of the optimal mixture of the EOs with conventional antibiotic ciprofloxacin against three pathogenic foodborne bacteria. Gas chromatography/mass spectrometry analysis showed that eucalyptol (39·05%), camphor (24·21%) and borneol (8·29%) were the dominant compounds of LA‐EO. LP‐EO was characterized by the abundance of camphor (74·51%) and fenchone (27·06%), whereas carvacrol (42·08%), camphor (17·95%) and fenchone (12·05%) were the main constituents of LM‐EO. EOs alone or combined showed a remarkable antimicrobial activity against the tested bacteria with minimum inhibitory concentrations (MICs) ranging from 3·53 to 15·96 mg ml−1. The optimal mixture, calculated using a mixture design, corresponded to 19% LA, 38% LP and 43% LM. All combination of the EOs and the best EO mixture with ciprofloxacin exhibited a total synergism with fractional inhibitory concentration index values ranging from 0·27 to 0·37. The best EO mixture showed the highest gain of 128‐fold, especially against Salmonella spp. , more than that found testing the EOs separately. These findings should be taken into consideration for a possible application in the pharmaceutical and food industries.
Correlation between cortical gene expression and resting‐state functional network centrality in healthy young adults

Resting‐state functional connectivity in the human brain is heritable, and previous studies have investigated the genetic basis underlying functional connectivity. However, at present, the molecular mechanisms associated with functional network centrality are still largely unknown. In this study, functional networks were constructed, and the graph‐theory method was employed to calculate network centrality in 100 healthy young adults from the Human Connectome Project. Specifically, functional connectivity strength (FCS), also known as the “degree centrality” of weighted networks, is calculated to measure functional network centrality. A multivariate technique of partial least squares regression (PLSR) was then conducted to identify genes whose spatial expression profiles best predicted the FCS distribution. We found that FCS spatial distribution was significantly positively correlated with the expression of genes defined by the first PLSR component. The FCS‐related genes we identified were significantly enriched for ion channels, axon guidance, and synaptic transmission. Moreover, FCS‐related genes were preferentially expressed in cortical neurons and young adulthood and were enriched in numerous neurodegenerative and neuropsychiatric disorders. Furthermore, a series of validation and robustness analyses demonstrated the reliability of the results. Overall, our results suggest that the spatial distribution of FCS is modulated by the expression of a set of genes associated with ion channels, axon guidance, and synaptic transmission.
Sex Differences in the Effects of COPD on Incidence and Outcomes of Patients Hospitalized with ST and Non-ST Elevation Myocardial Infarction: A Population-Based Matched-Pair Analysis in Spain (2016–2018)

We aimed to compare the incidence, clinical characteristics, and outcomes of patients admitted with myocardial infarction (MI), whether ST elevation MI (STEMI) or non-ST elevation MI (NSTEMI), according to the presence of chronic obstructive pulmonary disease (COPD), and to identify variables associated with in-hospital mortality (IHM). We selected all patients with MI (aged ≥40 years) included in the Spanish National Hospital Discharge Database (2016–2018). We matched each patient suffering COPD with a non-COPD patient with identical age, sex, type of MI, and year of hospitalization. We identified 109,759 men and 44,589 women with MI. The MI incidence was higher in COPD patients (incident rate ratio (IRR) 1.32; 95% confidence interval (CI) 1.29–1.35). Men with COPD had higher incidence of STEMI and NSTEMI than women with COPD. After matching, COPD men had a higher IHM than non-COPD men, but no differences were found among women. The probability of dying was higher among COPD men with STEMI in comparison with NSTEMI (odds ratio (OR) 2.33; 95% CI 1.96–2.77), with this risk being higher among COPD women (OR 2.63; 95% CI 1.75–3.95). Suffering COPD increased the IHM after an MI in men (OR 1.14; 95% CI 1.03–1.27), but no differences were found in women. COPD women had a higher IHM than men (OR 1.19; 95% CI 1.01–1.39). We conclude that MI incidence was higher in COPD patients. IHM was higher in COPD men than in those without COPD, but no differences were found among women. Among COPD patients, STEMI was more lethal than NSTEMI. Suffering COPD increased the IHM after MI among men. Women with COPD had a significantly higher probability of dying in the hospital than COPD men.
Differences in Clinical Characteristics and Chest Images between Coronavirus Disease 2019 and Influenza-Associated Pneumonia

Background: Concerns are arising about the simultaneous occurrence of the coronavirus disease 2019 (COVID-19) pandemic and the influenza epidemic, the so-called “twindemic”. In this study, we compared clinical characteristics and chest images from patients with COVID-19 and influenza. Methods: We conducted a case-control study of COVID-19 and age- and sex-matched influenza patients. Clinical characteristics and chest imaging findings between patients with COVID-19 and matched influenza patient controls were compared. Results: A total of 47 patients were enrolled in each group. Anosmia (14.9%) and ageusia (21.3%) were only observed in COVID-19 patients. There were 31 (66%) and 23 (48.9%) patients with COVID-19 and influenza who had pulmonary lesions confirmed by chest computed tomography (CT), respectively. The interval between symptom onset and pneumonia was significantly longer in patients with COVID-19. Round opacities were more common in images from COVID-19 patients (41.9% vs. 8.7%, p = 0.007), whereas pure consolidation (0% vs. 34.9%, p < 0.001) and pleural effusion (0% vs. 17.4%, p = 0.028) were more common in images from influenza patients. Notably, the difference in the number of involved pulmonary lobes observed on CT and pulmonary fields observed on radiographic images was significantly higher in COVID-19-associated pneumonia than that in influenza-associated pneumonia (2.32 ± 1.14 vs. 1.48 ± 0.99, p = 0.010). Conclusions: Chest images and thorough review of clinical findings could provide value for proper differential diagnoses of COVID-19 patients, but they are not sufficiently sensitive for initial diagnoses. In addition, chest radiography could underestimate COVID-19 lung involvement because of the lesion characteristics of COVID-19-associated pneumonia.
Experimental study of ion-drag pumping using various working fluids

An ion-drag pump in a vertical axisymmetric configuration was built. Different dielectric fluids were compared to establish which produced the best pumping performance. Experimental results showed that pumping performance depended on fluid properties, primarily fluid viscosity and electrical conductivity. Two fluids, dodecylbenzine and Envirotemp 200, were studied at various doping levels. In both fluids a decrease in the charge relaxation time caused a decrease in efficiency. >