Miracle-dz/UniFAR-FTUs huggingface dataset:
Cancer-Associated Fibroblasts Affect Intratumoral CD8+ and FoxP3+ T Cells Via IL6 in the Tumor Microenvironment

Purpose: Cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME) play a central role in tumor progression. We investigated whether CAFs can regulate tumor-infiltrating lymphocytes (TILs) and their role in tumor immunosuppression. Experimental Design: A total of 140 cases of esophageal cancer were analyzed for CAFs and CD8+ or forkhead box protein 3 (FoxP3+) TILs by IHC. We analyzed cytokines using murine or human fibroblasts and cancer cells. Murine-derived fibroblasts and cancer cells were also inoculated into BALB/c or BALB/c-nu/nu mice and the tumors treated with recombinant IL6 or anti-IL6 antibody. Results: CD8+ TILs and CAFs were negatively correlated in intratumoral tissues (P < 0.001), whereas FoxP3+ TILs were positively correlated (P < 0.001) in esophageal cancers. Cocultured Colon26 cancer cells and fibroblasts resulted in accelerated tumor growth in BALB/c mice, along with decreased CD8+ and increased FoxP3+ TILs, compared with cancer cells alone. In vitro, IL6 was highly secreted in both murine and human cancer cell/fibroblast cocultures. IL6 significantly increased Colon26 tumor growth in immune-competent BALB/c (P < 0.001) with fewer CD8+ TILs than untreated tumors (P < 0.001), whereas no difference in BALB/c-nu/nu mice. In contrast, FoxP3+ TILs increased in IL6-treated tumors (P < 0.001). IL6 antibody blockade of tumors cocultured with fibroblasts resulted not only in regression of tumor growth but also in the accumulation of CD8+ TILs in intratumoral tissues. Conclusions: CAFs regulate immunosuppressive TIL populations in the TME via IL6. IL6 blockade, or targeting CAFs, may improve preexisting tumor immunity and enhance the efficacy of conventional immunotherapies. Clin Cancer Res; 24(19); 4820–33. ©2018 AACR.
Mixed batches and symmetric discriminators for GAN training

Generative adversarial networks (GANs) are powerful generative models based on providing feedback to a generative network via a discriminator network. However, the discriminator usually assesses individual samples. This prevents the dis-criminator from accessing global distributional statistics of generated samples, and often leads to mode dropping: the generator models only part of the target distribution. We propose to feed the discriminator with mixed batches of true and fake samples, and train it to predict the ratio of true samples in the batch. The latter score does not depend on the order of samples in a batch. Rather than learning this invariance, we introduce a generic permutation-invariant discriminator architecture. This architecture is provably a universal approximator of all symmetric functions. Experimentally, our approach reduces mode collapse in GANs on two synthetic datasets, and obtains good results on the CIFAR10 and CelebA datasets, both qualitatively and quantitatively.
Köy ve Kasabalarda Görev Yapan Öğretmenlerin Mesleğin İlk Yılında Yaşadıkları Güçlükler

Bu calisma, koy ve kasabalarda mesleginin ilk yilini icra etmekte olan ogretmenlerin, ogretmenlik meslegine ve sosyal cevrelerine iliskin yasadiklari guclukleri ve bu gucluklerin demografik degiskenlere gore farklilik gosterip gostermedigini arastiran betimsel iliskisel bir tarama calismasidir. Calismanin orneklemini, kartopu ornekleme yontemiyle saptanan Turkiye’nin cesitli koy ve kasabalarinda gorev yapan toplam 210 aday ogretmen olusturmaktadir. Elde edilen veriler, betimsel ve cikarsamali istatistik yontemleriyle analiz edilmistir. Bulgulara gore, katilimci ogretmenler, meslegin ilk yilinda en cok is yuku, sosyal statu ve ogretmen kimligi, amirlerle iliskiler ve sinif yonetimine iliskin guclukler yasamaktadirlar. En az siklikta yasanan gucluk ise ogrencilerle iliskiler boyutu olmustur. Bu gucluklerin yasa, cinsiyete ve gorev yerine gore farklilik gostermedigi; fakat katilimcilarin ogretmenlik yaptigi egitim-ogretim kademesine ve ogretmenlik alanlarina gore farklilik gosterdigi gorulmustur.
Dissociations of cognitive inhibition, response inhibition, and emotional interference: Voxelwise ALE meta‐analyses of fMRI studies

Inhibitory control is the stopping of a mental process with or without intention, conceptualized as mental suppression of competing information because of limited cognitive capacity. Inhibitory control dysfunction is a core characteristic of many major psychiatric disorders. Inhibition is generally thought to involve the prefrontal cortex; however, a single inhibitory mechanism is insufficient for interpreting the heterogeneous nature of human cognition. It remains unclear whether different dimensions of inhibitory processes—specifically cognitive inhibition, response inhibition, and emotional interference—rely on dissociated neural systems. We conducted systematic meta‐analyses of fMRI studies in the BrainMap database supplemented by PubMed using whole‐brain activation likelihood estimation. A total of 66 study experiments including 1,447 participants and 987 foci revealed that while the left anterior insula was concordant in all inhibitory dimensions, cognitive inhibition reliably activated specific dorsal frontal inhibitory system, engaging dorsal anterior cingulate, dorsolateral prefrontal cortex, and parietal areas, whereas emotional interference reliably implicated a ventral inhibitory system, involving the ventral surface of the inferior frontal gyrus and the amygdala. Response inhibition showed concordant clusters in the fronto‐striatal system, including the dorsal anterior cingulate region and extended supplementary motor areas, the dorsal and ventral lateral prefrontal cortex, basal ganglia, midbrain regions, and parietal regions. We provide an empirically derived dimensional model of inhibition characterizing neural systems underlying different aspects of inhibitory mechanisms. This study offers a fundamental framework to advance current understanding of inhibition and provides new insights for future clinical research into disorders with different types of inhibition‐related dysfunctions.
Accuracy of electronic health record data for the diagnosis of chronic obstructive pulmonary disease in persons living with HIV and uninfected persons

No prior studies have addressed the performance of electronic health record (EHR) data to diagnose chronic obstructive pulmonary disease (COPD) in people living with HIV (PLWH), in whom COPD could be more likely to be underdiagnosed or misdiagnosed, given the higher frequency of respiratory symptoms and smoking compared with HIV‐uninfected (uninfected) persons.
Healthcare Resource Waste Associated with Patient Nonadherence and Early Discontinuation of Traditional Continuous Glucose Monitoring in Real-World Settings: A Multicountry Analysis

Abstract Background: Traditional continuous glucose monitoring (CGM) provides detailed information on glucose patterns and trends to inform daily diabetes management decisions, which is particularly beneficial for patients with a history of hypoglycemia unawareness. However, a high level of patient adherence (≥70%) is required to achieve clinical benefits. The aim of this study was to assess the impact of real-world patient nonadherence and early discontinuation on healthcare resource use. Methods: A cost calculator was designed to evaluate monthly healthcare resource waste within the first year of traditional CGM initiation by combining estimates of real-world nonadherence and early discontinuation from the literature with the wholesale acquisition costs of the current technology in the United States (for a commercial payer and for Medicare), or its equivalent in Sweden, Germany, or the Netherlands. Results: Based on an early discontinuation rate of 27% and nonadherence rates of 13.9%–31.1% over the 12 months following initiation, the healthcare resource waste associated with nonadherence and early discontinuation was $220,289 and $21,775, respectively, for every 100 patients initiating CGM in the U.S. commercial payer scenario. In the Medicare scenario, the corresponding figures were $72,648 and $5,675, respectively. In both scenarios, nonadherence and early discontinuation accounted for ∼24% of resources being wasted within the first year of CGM initiation. Similar results were observed using the local costs in the other countries analyzed. Conclusions: The healthcare resource waste associated with traditional CGM nonadherence and early discontinuation warrants deliberate consideration when selecting suitable patients for this technology.
Pore Structure Characterization of Sodium Hydroxide Activated Slag Using Mercury Intrusion Porosimetry, Nitrogen Adsorption, and Image Analysis

The pore structure of alkali-activated slag has a significant influence on its performance. However, the literature shows insufficient studies regarding the suitability of different techniques for characterizing the pore structure and the influences of Na2O and curing age on pore structure development. In pursuit of a better understanding, the pore structure of sodium hydroxide activated slag paste was characterized by multiple techniques, e.g., mercury intrusion porosimetry (MIP), nitrogen (N2) adsorption, and scanning electron microscopy (SEM) image analysis. The sodium hydroxide activated slag pastes were prepared with three different contents of Na2O (Na2O/slag = 4, 6, and 8%) and cured for different times up to 360 days. The microstructure observation reveals that outer C–(N–)A–S–H and inner C–(N–)A–S–H grow successively around the reacting slag grains, along with crystalline reaction products which are formed in the empty coarse pore space. The increase of Na2O content and curing age lead to a finer pore structure. The MIP measurements show that the total porosity drops about 70% within the first day, and that one peak at most, corresponding to gel pores, was identified in the differential curves of all the investigated samples from 1 to 360 days. On the contrary, only one peak, corresponding to capillary pores, was identified by SEM-image analysis. The differential curves derived from N2 adsorption generally reveal two peaks, and the trend that the pore diameters of those two peaks vary with curing age depends on the content of Na2O. Compared to Portland cement, sodium hydroxide activated slag has a higher pore space filling capacity (χ, Vproducts/Vslag-reacted), while the capacity decreases with increasing Na2O content and curing age.
The Barrow Biomimetic Spine: Comparative Testing of a 3D-Printed L4-L5 Schwab Grade 2 Osteotomy Model to a Cadaveric Model

Introduction The Barrow Biomimetic Spine project is an ongoing effort to develop a three-dimensional (3D)-printed synthetic spine model with high anatomical and biomechanical fidelity to human tissue. The purpose of this study was to evaluate the biomechanical performance of an L4-L5 3D-printed synthetic spine model in a lordotic correction test after Schwab grade 2 osteotomies as compared to human cadaveric spines that have undergone the same osteotomies and lordotic correction. Methods Ten different L4-L5 synthetic spine models were 3D printed. Each print varied in either the material used for the soft tissue components, the infill density of the bony and soft tissue structures, the pre-correction disc height, or the model orientation on the print bed. Each print was instrumented with pedicle screws and underwent a Schwab grade 2 osteotomy. Changes in disc height measurements and end-plate angle were compared against cadaveric data acquired using the same study method. Results A simple linear correlation analysis demonstrated that for horizontally printed models using PolyFlex (Polymaker, New York, NY, USA)(models 1-3, 8, 10), the pre-correction posterior disc height and lordotic correction were moderately correlated (r = 0.56), but this correlation did not achieve statistical significance (P = 0.12). Regression analysis demonstrated a very strong correlation between lordotic correction and change in posterior disc height (r = 0.92, P < 0.001). Models printed either vertically (models 4-6) or with low bone density and high soft tissue density (model 10) appeared to perform the most similarly to the cadaveric tissue. Discussion The 3D-printed synthetic spine models demonstrated predictable and reliable performance in a lordotic correction test based on their respective material qualities and print densities. The print variables tested further demonstrated that this model is capable of achieving high biomechanical fidelity to cadaveric tissue when subjected to the same lordotic correction test after Schwab grade 2 osteotomies.
Berberine protects the liver and kidney against functional disorders and histological damages induced by ferrous sulfate

Objective(s): Iron is an essential element for living organisms. Iron overload can have detrimental effects on health. This study pertains to the protective role of berberine against ferrous sulfate-induced hepatic and renal functional disorders and histological damages in rats. Materials and Methods: The rats were divided into four groups (n=7): Sham, Ber (10 mg/kg/day for 14 days, by gavage), FS (ferrous sulfate, 30 mg/kg/day for 14 days, intraperitoneally), FS + Ber (ferrous sulfate, 30 mg/kg/day for 14 days; berberine, 10 mg/kg/day for 11 days from fourth day of ferrous sulfate injection). After 24 hr, blood, urine, and tissue samples were collected. Results: Compared with sham and Ber groups, administration of ferrous sulfate resulted in liver and kidney dysfunction as evidenced by significantly higher levels of serum hepatic markers and bilirubin, and lower levels of serum albumin, total protein, triglyceride, cholesterol, and glucose, as well as lower creatinine clearance and higher fractional excretion of sodium. This was accompanied by increased malondialdehyde levels and histological damages. Berberine treatment significantly reversed the levels of serum hepatic markers, renal functional markers and lipid peroxidation marker in the FS + Ber group. Furthermore, it restored the levels of serum total protein, albumin, glucose, triglycerides, and cholesterol with a decrease in bilirubin concentration in the blood. All these changes were corroborated by histological observations of the liver and kidney. Conclusion: Berberine protects the liver and kidneys against ferrous sulfate-induced toxicity by reduction in lipid peroxidation and ability to chelate iron.
Weak Mutual Majority Criterion for Voting Rules Aleksei

We study a novel axiom for voting rules: the weak mutual majority criterion (WMM). A voting rule satisfies WMM if whenever some k candidates receive top k ranks from a qualified majority that consists of more than q = k/(k+1) of voters, the rule selects the winner among these k candidates. WMM lies between the two standard axioms: it is stronger than the majority criterion (here k = 1 and q = 1/2) and weaker than the mutual majority criterion (MM, here for any k the size of majority is fixed q = 1/2). The widespread plurality rule satisfies WMM (but not MM). Moreover, for any k the bound q = k/(k + 1) is tight. The plurality with runoff rule, the Dodgson’s rule, the Condorcet least reversal rule, the Simpson’s rule, and the Young’s rule satisfy WMM, for most of these rules we also find tight bounds on the size of the qualified majority q. The well-known Black’s rule and its positional version do not satisfy WMM: for k > 1 its tight bound q = 1. We propose two modifications of the Black’s positional rule that satisfy WMM: the qualified mutual majority rule with the tight bound q = k/(k+ 1) and the convex median voting rule with the tight bound q = (3k−1)/(4k).
Consumer Behaviour and Order Fulfilment in Online Retailing: A Systematic Review

This paper provides a systematic review of consumer behaviour and order fulfilment in online retailing. The objective of this review is threefold: first, to identify elements of order-fulfilment operations that are relevant to online consumer behaviour (purchase, repurchase, product return); second, to understand the relationship between order-fulfilment performance and consumer behaviour; and third, to inspire future research on developing consumer service strategies that takes account of these behavioural responses to order-fulfilment performance outcomes. The paper is based on a systematic review of literature on online consumer behaviour and order-fulfilment operations, mainly in the fields of marketing and operations, published in international peer-reviewed journals between 2000 and September 2015. This study indicates that the current literature on online consumer behaviour focuses mainly on the use of marketing tools to improve consumer service levels. Very little research has been conducted on the use of consumer service instruments to steer consumer behaviour or, consequently, to manage related order-fulfilment activities better. The study culminates in a framework that encompasses elements of order-fulfilment operations and their relationship to online consumer behaviour. This paper is the first comprehensive review of online consumer behaviour that takes aspects of order-fulfilment operations into account from both marketing and operations perspectives.
Use of Inpatient Behavioral Health Services by Children and Adolescents With Private Insurance Coverage.

OBJECTIVE This study examined trends in hospitalizations of youths for behavioral health conditions in acute care hospital nonpsychiatric beds, acute care hospital psychiatric and detoxification beds, and specialty psychiatric hospitals. METHODS Using data on hospitalizations for behavioral health conditions in 2009 (N=21,805) and 2014 (N=27,550) from the MarketScan Commercial Claims and Encounters database, this study examined the percentage of youths (ages two to 18) with one or more hospitalizations, by demographic characteristic and bed type, and the behavioral health diagnoses for which patients were hospitalized. RESULTS The greatest increase in hospitalizations of youths occurred in acute care hospital psychiatric and detoxification beds. The percentage of hospitalizations for suicidal ideation or self-harm injuries increased by 17.8 (N=526) to 30.0 (N=1,249) percentage points, depending on bed type. CONCLUSIONS The continued trend of rising hospitalizations of youths is consistent with recent studies showing a doubling of hospitalizations of youths for suicide and self-harm.
Uncertainty Driven Action (UDA) model: A foundation for unifying perspectives on design activity

This paper proposes the Uncertainty Driven Action (UDA) model, which unifies the fragmented literature on design activity. The UDA model conceptualises design activity as a process consisting of three core actions: information action, knowledge-sharing action, and representation action, which are linked via uncertainty perception. The foundations of the UDA model in the design literature are elaborated in terms of the three core actions and their links to designer cognition and behaviour, utilising definitions and concepts from Activity Theory. The practical relevance and theoretical contributions of the UDA model are discussed. This paper contributes to the design literature by offering a comprehensive formalisation of design activity of individual designers, which connects cognition and action, to provide a foundation for understanding previously disparate descriptions of design activity.
Thalamic white matter in multiple sclerosis: A combined diffusion‐tensor imaging and quantitative susceptibility mapping study

Thalamic white matter (WM) injury in multiple sclerosis (MS) remains relatively poorly understood. Combining multiple imaging modalities, sensitive to different tissue properties, may aid in further characterizing thalamic damage. Forty‐five MS patients and 17 demographically‐matched healthy controls (HC) were scanned with 3T MRI to obtain quantitative measures of diffusivity and magnetic susceptibility. Participants underwent cognitive evaluation with the Brief International Cognitive Assessment for Multiple Sclerosis battery. Tract‐based spatial statistics identified thalamic WM. Non‐parametric combination (NPC) analysis was used to perform joint inference on fractional anisotropy (FA), mean diffusivity (MD) and magnetic susceptibility measures. The association of surrounding WM lesions and thalamic WM pathology was investigated with lesion probability mapping. Compared to HCs, the greatest extent of thalamic WM damage was reflected by the combination of increased MD and decreased magnetic susceptibility (63.0% of thalamic WM, peak p = .001). Controlling for thalamic volume resulted in decreased FA and magnetic susceptibility (34.1%, peak p = .004) as showing the greatest extent. In MS patients, the most widespread association with information processing speed was found with the combination of MD and magnetic susceptibility (67.6%, peak p = .0005), although this was not evident after controlling for thalamic volume. For memory measures, MD alone yielded the most widespread associations (45.9%, peak p = .012 or 76.7%, peak p = .001), even after considering thalamic volume, albeit with smaller percentages. White matter lesions were related to decreased FA (peak p = .0063) and increased MD (peak p = .007), but not magnetic susceptibility, of thalamic WM. Our study highlights the complex nature of thalamic pathology in MS.
Investigation of Fluids in Macrocrystalline and Microcrystalline Quartz in Agate Using Thermogravimetry-Mass-Spectrometry

Gaseous and liquid fluids in agates (banded chalcedony—SiO2) of different localities were investigated systematically by thermogravimetry-mass-spectrometry within a temperature range from 25 to 1450 °C, for the first time. Chalcedony and macrocrystalline quartz from twelve agate samples were investigated, from Germany (Schlottwitz, St. Egidien, Chemnitz and Zwickau), Brazil (Rio Grande do Sul), Scotland (Ayrshire) and the USA (Montana). They originate from mafic and felsic volcanic rocks as well as hydrothermal and sedimentary environments. The results were evaluated regarding compounds of hydrogen with fluorine, chlorine, nitrogen, carbon and sulphur. Additionally, oxygen compounds were recognized with hydrogen, fluorine, nitrogen, sulphur and carbon. The nature of the compounds was identified based on their mass-charge-ratio and the intensity ratios of the associated fragments. Due to interferences of different compounds with the same mass-charge-ratio, only H2O, HF, NO, S, SO, CO3—as well as several hydrocarbon compounds (for example CO32− or CO)—could be properly identified. The main degassing temperatures were detected at around 500 and 1000 °C. Generally, a difference between quartz and chalcedony regarding the composition of their fluids could not be found. The results indicate a silica source for the agate formation from aqueous solutions but also a possible role of fluorine compounds. Additionally, CO2 and other fluids were involved in the alteration of volcanic rocks and the mobilization and transport of SiO2.
Deep Neural Decision Trees

Deep neural networks have been proven powerful at processing perceptual data, such as images and audio. However for tabular data, tree-based models are more popular. A nice property of tree-based models is their natural interpretability. In this work, we present Deep Neural Decision Trees (DNDT) -- tree models realised by neural networks. A DNDT is intrinsically interpretable, as it is a tree. Yet as it is also a neural network (NN), it can be easily implemented in NN toolkits, and trained with gradient descent rather than greedy splitting. We evaluate DNDT on several tabular datasets, verify its efficacy, and investigate similarities and differences between DNDT and vanilla decision trees. Interestingly, DNDT self-prunes at both split and feature-level.