Miracle-dz/UniFAR-FTUs huggingface dataset:
A novel 6-gene signature derived from tumor-infiltrating T cells and neutrophils predicts survival of bladder urothelial carcinoma

Intratumoral immune cells were reported to be associated with prognosis of bladder urothelial carcinoma (BUC). However, the role of immune cells related genes in BUC prognosis is less well defined. In the study, we analyzed data retrieved from the Cancer Genome Atlas database and found higher neutrophils and lower T cells infiltration in BUC tumor tissues were significantly correlated with patients’ worse prognosis. Additionally, the expression levels of 164 genes were significantly correlated with T cells and neutrophils proportions. A Cox proportional-hazards model integrating 6 genes expression (EMP1, RASGRP4, HSPA1L, AHNAK, SLC1A6, and PRSS8) was identified. The 6-gene signature outperformed other clinical factors in risk prediction and was an independent prognostic factor for BUC. The findings were further conformed in three Gene Expression Omnibus datasets (n=331) and Jiangsu Province Hospital cohort (n = 46). Gene set enrichment analysis revealed that the model was highly involved in some immune-related pathways. A comprehensive nomogram combining the model and other clinical parameters was finally constructed to facilitate clinical application. In conclusion, a T cell and neutrophil-associated 6-gene prognostic model was identified for the survival prediction of BUC patients.
Randomised controlled trial to investigate optimal antithrombotic therapy in patients with non-valvular atrial fibrillation undergoing percutaneous coronary intervention: a study protocol of the OPTIMA-AF trial

Introduction The optimal antithrombotic strategy for patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) is uncertain. For patients with non-AF, many trials are now evaluating short 1-month dual antiplatelet therapy. In patients with AF undergoing PCI, in contrast, short dual therapy (P2Y12 inhibitor +direct oral anticoagulant (DOAC)) has not yet been evaluated. Methods and analysis The OPTIMA-AF trial (OPTIMAl antiplatelet therapy in combination with direct oral anticoagulants in patients with non-valvular Atrial Fibrillation undergoing percutaneous coronary intervention with everolimus-eluting stent) is an investigator-initiated, open-label, nationwide, multicentre, prospective, randomised controlled trial. The primary objective is to compare the efficacy and safety of short dual therapy (1-month DOAC +P2Y12 inhibitor followed by DOAC monotherapy) against long dual therapy (12-month DOAC +P2Y12 inhibitor followed by DOAC monotherapy) in the treatment of AF subjects undergoing PCI. The primary efficacy endpoint is a composite of death or thromboembolic events (myocardial infarction, definite stent thrombosis, stroke or systemic embolism) at 365 days; and the primary safety endpoint is bleeding (International Society on Thrombosis and Haemostasis major or clinically relevant non-major bleeding) at 365 days. This trial is intended to show the non-inferiority of short dual therapy versus long dual therapy in terms of the primary efficacy endpoint and show superiority in terms of the primary safety endpoint. A total of 1090 subjects will be randomised in a 1:1 ratio at approximately 60 sites. Ethics and dissemination This study received approval from the Certified Review Board of Osaka University (a certified research ethics committee by the Japanese Clinical Research Act). The findings will be disseminated through peer-reviewed publications and conference presentations. Trial registration number Japan Registry of Clinical Trials: jRCTs051190053; Pre-results.
Hyporexia and cellular/biochemical characteristics of pleural fluid as predictive variables on a model for pleural tuberculosis diagnosis

ABSTRACT Objectives Pleural tuberculosis (PlTB) diagnosis is a challenge due to its paucibacillary nature and to the need of invasive procedures. This study aimed to identify easily available variables and build a predictive model for PlTB diagnosis which may allow earlier and affordable alternative strategy to be used in basic health care units. Methods An observational cross-sectional study compared PlTB and non-TB patients followed at a tertiary Brazilian hospital between 2010 and 2018. Unconditional logistic regression analysis was performed and a Decision Tree Classifier (DTC) model was validated and applied in additional PlTB patients with empiric diagnosis. The accuracy (Acc), sensitivity (Se), specificity (Sp), positive and negative predictive values were calculated. Results From 1,135 TB patients, 160 were considered for analysis (111 confirmed PlTB and 49 unconfirmed PlTB). Indeed, 58 non-TB patients were enrolled as controls. Hyporexia [adjusted odds ratio (aOR) 27.39 (95% CI 6.26 – 119.89)] and cellular/biochemical characteristics on pleural fluid (PF) (polimorphonuclear in two categories: 3-14% aOR 26.22, 95% CI 7.11 – 96.68 and < 3% aOR 28.67, 95% CI 5.51 – 149.25; and protein ≥ 5g/dL aOR 7.24, 95% CI 3.07 – 17.11) were associated with higher risk for TB. The DTC constructed using these variables showed Acc=87.6%, Se=89.2%, Sp=84.5% for PlTB diagnosis and was successfully applied in unconfirmed PlTB patients. Conclusion The DTC model showed an excellent performance for PlTB diagnosis and can be considered as an alternative diagnostic strategy by using clinical patterns in association with PF cellular/biochemical characteristics, which were affordable and easily performed in basic health care units.
Tuberculosis: First in Flight

over is the heterogeneity of the study population. Fifty-four percent of subjects had diaphragm pacing, 81% had a tracheostomy, and 48% were mechanically ventilated during HUT testing. It is likely that the interactions between breathing and the autonomic control of the cardiovascular system in individuals who are breathing spontaneously differ from those requiring ventilatory assistance. A standardized clinical management of individuals with CCHS and data collection across centers may be the only approach to overcome the limitations imposed by retrospective single-center studies.
Characterization of clinical, laboratory, IL-6 serum levels, and IL-6-174 G/C genetic polymorphisms in patients with rheumatoid arthritis and Sjögren's syndrome.

OBJECTIVE This study aimed to characterize the clinical (disease activity and exocrine gland function), laboratory, interleukin 6 (IL-6) serum levels, and IL-6-174G/C (rs1800795) genetic polymorphisms among rheumatoid arthritis (RA), RA plus Sjögren's syndrome (RA+SS), and control subjects. METHODS A case-control study enrolling 137 women (52±11 years old) were divided into three groups as follows: RA (n=70), RA+SS (n=29), and healthy control (C, n=38). Individuals underwent clinical evaluation composed of Schirmer's test, unstimulated salivary flow rate, and evaluation of disease activity and functional capacity (Disease Activity Score [DAS28] and Health Assessment Questionnaire [HAQ]). IL-6 serum levels and IL-6-174G/C polymorphisms were assessed. RESULTS RA and RA+SS presented higher serum levels of IL-6 than controls (p<0.001). Also, higher IL-6 levels were related to swollen joints (p=0.038), limited functional capacity (p=0.004), and disease activity (p≤0.001). However, neither IL-6-174G/C genetic polymorphism nor its allele frequency was associated with RA or RA+SS. CONCLUSION IL-6 serum is an important marker of RA activity and functional incapacity, but IL-6-174G/C genetic polymorphism did not differ among healthy controls and cases.
Long‐term outcomes in corticosteroid‐refractory Graves' orbitopathy treated with tocilizumab

Up to 20% of patients with moderate to severe Graves' orbitopathy (GO) do not respond to high‐dose glucocorticoids (GC). A few studies, including a randomized trial, have demonstrated the efficacy of interleukin‐6 (IL‐6) blockade with tocilizumab (TCZ) in GC‐refractory GO. However, data on predictors of response to TCZ and long‐term outcomes are lacking.
When tropical and subtropical congeners met: Multiple ancient hybridization events within Eriobotrya in the Yunnan‐Guizhou Plateau, a tropical‐subtropical transition area in China

Global climate changes during the Miocene may have created ample opportunities for hybridization between members of tropical and subtropical biomes at the boundary between these zones. Yet, very few studies have explored this possibility. The Yunnan‐Guizhou Plateau (YGP) in Southwest China is a biodiversity hotspot for vascular plants, located in a transitional area between the floristic regions of tropical Southeast Asia and subtropical East Asia. The genus Eriobotrya (Rosaceae) comprises both tropical and subtropical taxa, with 12 species recorded in the YGP, making it a suitable basis for testing the hypothesis of between‐biome hybridization. Therefore, we surveyed the evolutionary history of Eriobotrya by examining three chloroplast regions and five nuclear genes for 817 individuals (47 populations) of 23 Eriobotrya species (including 19 populations of 12 species in the YGP), plus genome re‐sequencing of 33 representative samples. We concluded that: (1) phylogenetic positions for 16 species exhibited strong cytonuclear conflicts, most probably due to ancient hybridization; (2) the YGP is a hotspot for hybridization, with 11 species showing clear evidence of chloroplast capture; and (3) Eriobotrya probably originated in tropical Asia during the Eocene. From the Miocene onwards, the intensification of the Eastern Asia monsoon and global cooling may have shifted the tropical‐subtropical boundary and caused secondary contact between species, thus providing ample opportunity for hybridization and diversification of Eriobotrya, especially in the YGP. Our study highlights the significant role that paleoclimate changes probably played in driving hybridization and generating rich species diversity in climate transition zones.
Exploring the Potential of Stem Cell-Based Therapy for Aesthetic and Plastic Surgery

Over the last decade, stem cell-associated therapies are widely used because of their potential in self-renewable and multipotent differentiation ability. Stem cells have become more attractive for aesthetic uses and plastic surgery, including scar reduction, breast augmentation, facial contouring, hand rejuvenation, and anti-aging. The current preclinical and clinical studies of stem cells on aesthetic uses also showed promising outcomes. Adipose-derived stem cells are commonly used for fat grafting that demonstrated scar improvement, anti-aging, skin rejuvenation properties, etc. While stem cell-based products have yet to receive approval from the FDA for aesthetic medicine and plastic surgery. Moving forward, the review on the efficacy and potential of stem cell-based therapy for aesthetic and plastic surgery is limited. In the present review, we discuss the current status and recent advances of using stem cells for aesthetic and plastic surgery. The potential of cell-free therapy and tissue engineering in this field is also highlighted. The clinical applications, advantages, and limitations are also discussed. This review also provides further works that need to be investigated to widely apply stem cells in the clinic, especially in aesthetic and plastic contexts.
Design in the Learning Organization: Educating for the New Culture of Product Development

PERHAPS NO ORGANIZATION is more compartmentalized than a university, but among universities, Carnegie Mellon's interdisciplinary design programs are truly distinctive. Richard Buchanan and Craig Vogel detail the collaborations among faculty, students, and corporate partners, during the past decade, to develop courses that explore the potential for genuine cross-functional communication and cooperation, and they highlight strategies fundamental to the success of the endeavor.
Critical Analysis of Time and Cost of Management and Traditional Contracts

This paper presents some findings of a PhD research program conducted by Naoum in 1989, which sought to investigate whether the means of procurement influenced project performance. Ten factors were identified to measure project performance: (1) Preconstruction time; (2) construction time; (3) total time; (4) speed of construction; (5) unit cost of building; (6) time overrun; (7) cost overrun; and client satisfaction with (8) time, (9) cost, and (10) quality. A theoretical framework was used to assist in comparing project performance in a case study sample of 39 management contracts and 30 traditional contracts. From the evidence available in the writer's study, it must be concluded that in neither the management nor the traditional system lies the solution to all the problems facing the construction industry. To achieve project success, the parties need to match the various organizational forms to the client's characteristics, criteria, and priorities with respect to time, cost, and quality. The statistic.
Long-Term Effects of Prematurity on Resting Ventilatory Response to Hypercapnia.

Manferdelli, Giorgio, Benjamin J. Narang, Mathias Poussel, Damjan Osredkar, Grégoire P. Millet, and Tadej Debevec. Long-term effects of prematurity on resting ventilatory response to hypercapnia. High Alt Med Biol. 22:420-425, 2021. Background: This study investigated the resting ventilatory response to hypercapnia in prematurely born adults. Materials and Methods: Seventeen preterm and fourteen full-term adults were exposed to normoxic hypercapnia (two 5-minute periods at 3% and 6% carbon dioxide [CO2] interspersed by 5-minute in normoxia). Pulmonary ventilation ([Formula: see text]) and end-tidal partial pressure of CO2 (Petco2) were measured continuously. Results: No difference in lung function was observed between preterm and full-term adults. Petco2 was lower in preterm than in full-term adults (p < 0.05) during normoxia. During exposure to 3% CO2, both [Formula: see text] and Petco2 increased in a similar way in preterm and full-term adults. However, at the end of the 6% CO2 period, there was a significantly higher [Formula: see text] in preterm compared with full-term adults (30.2 ± 7.5 vs. 23.7 ± 4.5 L/min, p < 0.0001), whereas no difference was observed for Petco2 (46.9 ± 2.1 vs. 50.6 ± 2.1 L/min, p = 0.99). Breath frequency was higher in preterm than in full-term adults (17.9 ± 4.0 vs. 12.8 ± 3.5 b/min, p < 0.01) during 6% CO2 exposure. Conclusions: Although data suggest that prematurity results in resting hypocapnia, the exact underlying mechanisms remain to be elucidated. Moreover, preterm adults seem to have increased chemosensitivity to hypercapnia.
Magnetic resonance imaging of cerebrospinal fluid outflow after low-rate lateral ventricle infusion in mice

The anatomical routes for the clearance of cerebrospinal fluid (CSF) remain incompletely understood. However, recent evidence has given strong support for routes leading to lymphatic vessels. A current debate centers upon the routes through which CSF can access lymphatics, with evidence emerging for either direct routes to meningeal lymphatics or along cranial nerves to reach lymphatics outside the skull. Here, a method was established to infuse contrast agent into the ventricles using indwelling cannulae during imaging of mice at 2 and 12 months of age by magnetic resonance imaging. As expected, a substantial decline in overall CSF turnover was found with aging. Quantifications demonstrated that the bulk of the contrast agent flowed from the ventricles to the subarachnoid space in the basal cisterns. Comparatively little contrast agent signal was found at the dorsal aspect of the skull. The imaging dynamics from the 2 cohorts revealed that the contrast agent was cleared from the cranium through the cribriform plate to the nasopharyngeal lymphatics. On decalcified sections, we confirmed that fluorescently labeled ovalbumin drained through the cribriform plate and could be found within lymphatics surrounding the nasopharynx. In conclusion, routes leading to nasopharyngeal lymphatics appear to be a major efflux pathway for cranial CSF.
Phosphoinositides containing stearic acid are required for interaction between Rho GTPases and the exocyst to control the late steps of polarized exocytosis

Cell polarity is achieved by regulators such as small G proteins, exocyst members and phosphoinositides, with the latter playing a key role when bound to the exocyst proteins Sec3p and Exo70p, and Rho GTPases. This ensures asymmetric growth via the routing of proteins and lipids to the cell surface using actin cables. Previously, using a yeast mutant for a lysophosphatidylinositol acyl transferase encoded by the PSI1 gene, we demonstrated the role of stearic acid in the acyl chain of phosphoinositides in cytoskeletal organization and secretion. Here, we use a genetic approach to characterize the effect on late steps of the secretory pathway. The constitutive overexpression of PSI1 in mutants affecting kinases involved in the phosphoinositide pathway demonstrated the role of molecular species containing stearic acid in bypassing a lack of phosphatidylinositol‐4‐phosphate (PI(4)P) at the plasma membrane, which is essential for the function of the Cdc42p module. Decreasing the levels of stearic acid‐containing phosphoinositides modifies the environment of the actors involved in the control of late steps in the secretory pathway. This leads to decreased interactions between Exo70p and Sec3p, with Cdc42p, Rho1p and Rho3p, because of disruption of the GTP/GDP ratio of at least Rho1p and Rho3p GTPases, thereby preventing activation of the exocyst.
Efficacy of environmental and supplier relationship investments—moderating effects of external environment

Supply chains competing today seemingly have to be able to cut costs in the face of global competition while simultaneously keeping up with rapid technological change. External stakeholders have much higher expectations in terms of environmental and social performance than they did in the past. This research is an initial step in directing operational investments in this new, complicated marketplace. Specifically we examine the efficacy of investing in buyer supplier relationships and environmental management while controlling for the competitive environment. A significant contribution of this research is that operational performance is not treated as a uni-dimensional construct. The end result is a more complete understanding of the specific performance benefits of each type of investment.
Inheritance of ear yield and its components in sweet corn (Zea mays L. saccharat)

Sweet corn is mutation of field corn in which greater accumulation of sugars and water soluble polysaccharides provide specific taste and texture. It is consumed in the milky stage of the endosperm, so the product’s quality and its appearance are important as well as ear yield. That is why breeders pay the same attention to these traits in breeding process. In this paper we analyzed combining ability and mode of inheritance of ear yield and yield components in sweet corn, such as kernel-row number, and ear length, by the use of diallel crosses of six sweet corn inbred lines. ANOVA showed that estimates of general (GCA) and specific (SCA) combining abilities were highly significant (p<0.01) for all observed traits. Nonaditive gene effects were more significant in the expression of ear yield and ear length, while additive gene effects were more important for kernel-row number. Analysis of components of genetic variance was in agreement with the results of ANOVA of combining ability. The mode of inheritance of kernel-row number was partial dominance, while overdominance was of greater importance for ear yield, and ear length. Inbred line L4 was indicted as the most desirable, among the examined set of inbreds, in the further sweet corn breeding programs, due to its significant GCA effects concerning ear yield and number of kernels per ear, and ear yield performances of the hybrids in which one of the components was this inbred, according to SCA and hetrosis estimates.
Multiphysics Simulations for Tunability Efficiency Evaluation of Liquid Crystal Based RF

This paper shows, based on a developed simulation tool, the results of a parametric study of different transmission line topologies regarding the tuning efficiency when controllable anisotropic dielectrics are used. At first a short introduction of the properties of liquid crystals (LC), representing such a controllable dielectric, is given as well as the theoretical models used for the physical simulation of LCs. Particular attention is turned to the implementation of the electric field solver which can handle fully anisotropic materials on non-uniformly spaced grids and how the electrical solver interacts with the physical simulation of the LC. The entire scheme is applied to study the tuning efficiency of different line types and dimension parameters which include a comparison withmeasured results. Subsequently, a new tuning concept, based on quasi orthogonal electric bias fields, is introduced and analyzed. Index Terms – Liquid crystal devices, Microwave phase shifters, Tunable circuits and devices, Finite Differences Method, Anisotropic media
A Tutorial on Bayesian Data Assimilation

This tutorial provides a broad introduction to Bayesian data assimilation that will be useful to practitioners, in interpreting algorithms and results, and for theoretical studies developing novel schemes with an understanding of the rich history of geophysical data assimilation and its current directions. The simple case of data assimilation in a 'perfect' model is primarily discussed for pedagogical purposes. Some mathematical results are derived at a high-level in order to illustrate key ideas about different estimators. However, the focus of this work is on the intuition behind these methods, where more formal and detailed treatments of the data assimilation problem can be found in the various references. In surveying a variety of widely used data assimilation schemes, the key message of this tutorial is how the Bayesian analysis provides a consistent framework for the estimation problem and how this allows one to formulate its solution in a variety of ways to exploit the operational challenges in the geosciences.
He ii Lyα Transmission Spikes and Absorption Troughs in Eight High-resolution Spectra Probing the End of He ii Reionization

We present statistics of He ii Lyα transmission spikes and large-scale absorption troughs using archival high-resolution (R = λ/Δλ ≃ 12,500–18,000) far-UV spectra of eight He ii-transparent quasars obtained with the Cosmic Origins Spectrograph on the Hubble Space Telescope. The sample covers the redshift range 2.5 ≲ z ≲ 3.8, thereby probing the rapidly evolving He ii absorption at the end of He ii reionization epoch. The measured lengths of the troughs decrease dramatically from L ≳ 100 cMpc at z > 3 to L ≃ 30 cMpc at z ∼ 2.7, signaling a significant progression of He ii reionization at these redshifts. Furthermore, unexpectedly long L ∼ 65 cMpc troughs detected at z ≃ 2.9 suggest that the UV background fluctuates at larger scales than predicted by current models. By comparing the measured incidence of transmission spikes to predictions from forward-modeled mock spectra created from the outputs of a (146 cMpc)3 optically thin Nyx hydrodynamical simulation employing different UV background models, we infer the redshift evolution of the He ii photoionization rate ΓHe II (z). The photoionization rate decreases with increasing redshift from ≃ 4.6 × 10−15 s−1 at z ≃ 2.6 to ≃ 1.2 × 10−15 s−1 at z ≃ 3.2, in agreement with previous inferences from the He ii effective optical depth, and following expected trends of current models of a fluctuating He ii-ionizing background.