Miracle-dz/UniFAR-FTUs huggingface dataset:
Artiﬁcial Intelligence for Histology-Based Detection of Microsatellite Instability and Prediction of Response to Immunotherapy in Colorectal Cancer

Simple Summary: Defects in a DNA repair pathway called mismatch repair (MMR) can lead to cancer, including colorectal cancer (CRC). The detection of mismatch repair deﬁciency (dMMR) is based on molecular tests, one of which is microsatellite instability (MSI) testing. Detecting tumors with dMMR/MSI is important for the identiﬁcation of patients with Lynch Syndrome and determining if patients may beneﬁt from immunotherapy. Recently, artiﬁcial intelligence has been evaluated as a method to predict MSI/dMMR directly from tissue slides that are available for most cancer patients. We review the data regarding the utility of machine learning for dMMR/MSI classiﬁcation, including its accuracy and limitations, focusing on CRC. We also provide an overview of previous efforts to predict MSI from tissue slides and background regarding the use of artiﬁcial intelligence for image analyses. We summarize recent efforts to use artiﬁcial intelligence for the prediction of MSI and discuss the implications for predicting response to immunotherapy. Abstract: Microsatellite instability (MSI) is a molecular marker of deﬁcient DNA mismatch repair (dMMR) that is found in approximately 15% of colorectal cancer (CRC) patients. Testing all CRC patients for MSI/dMMR is recommended as screening for Lynch Syndrome and, more recently, to determine eligibility for immune checkpoint inhibitors in advanced disease. However, universal testing for MSI/dMMR has not been uniformly implemented because of cost and resource limitations. Artiﬁcial intelligence has been used to predict MSI/dMMR directly from hematoxylin and eosin (H&E) stained tissue slides. We review the emerging data regarding the utility of machine learning for MSI classiﬁcation, focusing on CRC. We also provide the clinician with an introduction to image analysis with machine learning and convolutional neural networks. Machine learning can predict MSI/dMMR with high accuracy in high quality, curated datasets. Accuracy can be signiﬁcantly decreased when applied to cohorts with different ethnic and/or clinical characteristics, or different tissue preparation protocols. Research is ongoing to determine the optimal machine learning methods for predicting MSI, which will need to be compared to current clinical practices, including next-generation sequencing. Predicting response to immunotherapy remains an unmet need.
D IFFERENCES I N P SYCHOLOGICAL P ROBLEMS B ETWEEN L OW A ND H IGH A CHIEVING S TUDENTS

This study was conducted to examine the differences between low and high achieving students in their psychological problems i.e. depression, anxiety, and stress. 120 undergraduate students of the International Islamic University Malaysia (IIUM) were involved in this study. The Depression Anxiety Stress Scale (DASS) was used to measure the level of depression, anxiety, and stress among students. Independent Sample T-test was used to differentiate the level of psychological problems between low and high achieving students. The findings of this study revealed that there were significant differences between low and high achieving students in their psychological problems. The findings of the study will be useful in assisting educators, counselors, psychologist, and researchers to develop strategies to enhance students’ psychological well-being. This shows that depression affect the performance of the students i.e. the higher the depression, the lower is the academic achievement of the students. significantly more likely to score lower on measures of academic achievement and peer acceptance. Longitudinal analyses revealed that high-anxious students, compared to their low-anxious peers, scored significantly lower on measures of academic achievement , aggression, and peer acceptance.
Evidence for the presence of smooth muscle (cid:97) -actin within pericytes of the renal medulla

Evidence for the presence of smooth muscle (cid:97) -actin within pericytes of the renal medulla. Am. J. Physiol. 273 ( Regulatory Integrative Comp. Physiol. 42): R1742–R1748, 1997. —This study was designed to determine whether smooth muscle (cid:97) -actin mRNA and smooth muscle (cid:97) -actin contractile protein elements were present within the renal medullary pericytes. Extraction of total RNA from microdissected outer medullary descending vasa recta allowed for the detection of smooth muscle (cid:97) -actin mRNA expression using reverse transcription-polymerase chain reac- tion (RT-PCR). Expression of smooth muscle (cid:97) -actin was speciﬁc to the descending vasa recta and not a result of tubular contamination because RT-PCR ampliﬁcation of the vasopressin V 2 receptor, which is a speciﬁc tubular marker, did not occur. To determine the exact cell type(s) that trans-late the mRNAinto protein, we performed immunohistochem- istry on the renal outer and inner medulla using a monoclonal smooth muscle (cid:97) -actin antibody, whose speciﬁcity was determined by immunoblot analysis. Smooth muscle (cid:97) -actin protein was found selectively within the pericytes surrounding the descending vasa recta from the outer and inner medullary tissue sections. This study demonstrates that the pericytes alone that surround the descending vasa recta within the outer and inner medulla contain smooth muscle (cid:97) -actin mRNA and protein and are therefore the site of the contrac- tile elements that could play a vasomodulatory role in the control of renal medullary blood ﬂow and its distribution within the renal medulla.
European The distributional implications of asymmetric income dynamics

Income dynamics differ between groups of households deﬁned by whether the head has university education or not and have changed asymmetrically in Great Britain since 2008. Using a heterogeneous agent incomplete markets model, we examine the quantitative im- plications of these differences for wealth inequality and for the distribution of conditional welfare losses. Within-group wealth inequality is higher for the non-university group and has increased since 2008 for both groups, while between-group inequality has also increased. Welfare losses are signiﬁcantly higher for the non-university educated since 2008, and are driven by both a greater fall in mean income and a larger rise in income risk. Non-university educated households, which had initial wealth below the median and net labour income in the lower quintiles, suffered bigger losses. Social insurance policies be-yond those currently in place can mitigate such welfare losses via tax and beneﬁt redis- tributive mechanisms. For the broad majority of households, social insurance is valued more when it insures against the big adverse income shocks. asymmetric changes in income dynamics, since 2008, on the distribution of conditional welfare losses for these groups. This is motivated by empirical evidence for Great Britain which shows differences in income dynamics between households that vary with respect to university education. Focusing on groups of households whose head has a university education or not, wealth data from the Wealth and Asset Survey (WAS) 2006–2016 reveals that wealth inequality is higher for the non-university educated group, and that both between and within group inequality have increased since the ﬁrst wave of WAS in 20 06–20 08. Using income data from the British Household Panel Study (BHPS) 1991–2008 and WAS 2010–2016, we also ﬁnd differences in the net labour income processes between groups and that these
Phenotypic Changes in Lymphoid and Nonlymphoid Cells Induced by LP-BM 5 MuLV

The Laterjet-Duplan strain of radiation murine leukemia virus (MuLV) l differs from most other virus isolates in that it induces nonthymic rather than thymic lymphomas in mice (1). Haas and co-workers (2, 3) demonstrated that cell-free extracts produced from "reticulum cell neoplasms" (RCN) of mice infected with this agent contained a mixture of ecotropic, xenotropic, and mink cell focus (MCF)-inducing (4) MuLV. A cell line derived from bone marrow, termed RCNBM5, has served as a source of these viruses in subsequent studies, which suggested that the lymphomagenic component in the virus mixture was an MCFinducing MuLV (3, 5). Young adult mice infected with phenotypic mixtures of a nonpathogenic ecotropic virus and the MCF virus rapidly developed lymphadenopathy and splenomegaly, and died with massive enlargement of these tissues (2, 3, 5). Although initial histologic studies of tissues from virus-infected mice yielded the diagnosis of RCN type B (2), according to Dunn's (6) classification of murine hematopoietic tumors, later studies (5) indicated that the mice developed a polycional proliferation of B cells that may not be truly malignant. The splenic and nodal lesions, while classified as polyclonal immunoblastic B cell lymphomas, could not be transplanted, contained diploid cells throughout the course of the disease, and were rarely invasive of nonlymphoid tissues. Since, by these criteria, the lesions induced by the viruses in RCN-BM5 are non-neoplastic, the term "reticulum cell neoplasm" appears to be inappropriate. To indicate the nonmalignant lymphoproliferative nature of this disease, we will refer to the MuLV mixture from the BM5 tissue culture line as LP (lymphoproliferative)-BM5.
Anti-CD20 Therapy in TNF-Transgenic Mice and Are Targets of the Onset of Inflammatory-Erosive Arthritis Inflamed Lymph Nodes Are Associated with B Cells in hi /CD21+ Expanded CD23

Anti-CD20 B cell depletion therapy (BCDT) is very effective for some patients with rheumatoid arthritis (RA); however the pathogenic role of B lymphocytes in RA and the primary targets of BCDTare unknown. The human TNF transgenic (hTNF-Tg) mouse model of RA displays a chronic, progressive disease that spreads from distal to proximal joints and is generally considered to be adaptive immune system independent. We have previously reported that knee arthritis in hTNF-Tg mice is accompanied by structural and functional changes of the adjoining popliteal lymph node (PLN), detectable by contrast-enhanced magnetic resonance imaging. To better understand these changes, in this paper we show that onset of knee synovitis and focal erosions are paralleled by PLN contraction and accumulation of large numbers of B cells in the lymphatic sinus spaces within the node. Flow cytometry from TNF-Tg mice 2, 4–5, and 8–12 mo old demonstrated that B cell accumulation in the PLN follows ankle arthritis, but commences before knee disease, and involves early expansion of CD21 hi , CD23 + , IgM hi , CD1d + , activation marker-negative, polyclonal B cells that are found to be speciﬁcally restricted to lymph nodes draining inﬂamed, arthritic joints. The same B cell population also accumulates in PLNs of K/BxN mice with autoantigen-dependent arthritis. Strikingly, we show that BCDT ameliorates hTNF-Tg disease and clears follicular and CD21 hi , CD23 + B cells from the PLNs. On the basis of these ﬁndings, we propose a model whereby B cells contribute to arthritis in mice, and possibly RA, by directly affecting the structure, composition, and function of joint-draining lymph nodes. The Journal of Immunology , 2010, 184: 6142–6150. a covariate) ﬁxed synovial LNCap, two-sided t p signiﬁcant.
MicrostructuresInvolving Formation of Endothelial Surface A Chemokine Self-Presentation Mechanism

Endothelial surface microstructures have been described previously under inﬂammatory conditions; however, they remain ill-characterized. In this study, CXCL8, an inﬂammatory chemokine, was shown to induce the formation of ﬁlopodia-like protrusions on endothelial cells; the same effects were observed with CXCL10 and CCL5. Chemokines stimulated ﬁlopodia formation by both microvascular (from bone marrow and skin) and macrovascular (from human umbilical vein) endothelial cells. Use of blocking Abs and degradative enzymes demonstrated that CXCL8-stimulated ﬁlopodia formation was mediated by CXCR1 and CXCR2, Duffy Ag/receptor for chemokines, heparan sulfate (HS), and syndecans. HS was present on ﬁlopodial protrusions appearing as a meshwork on the cell surface, which colocalized with CXCL8, and this glycosaminoglycan was 2,6- O – and 3- O –sulfated. Transmission electron microscopy revealed that CXCL8-stimulated ﬁlopodial and microvilli-like protrusions that interacted with leukocytes before transendothelial migration and removal of HS reduced this migration. iTRAQ mass spectrometry showed that changes in the levels of cytoskeletal, signaling, and extracellular matrix proteins were associated with CXCL8-stimulated ﬁlopodia/microvilli formation; these included tropomyosin, fascin, and Rab7. This study suggests that chemokines stimulate endothelial ﬁlopodia and microvilli formation, leading to their presentation to leukocytes and leukocyte transendothelial migration. The Journal of Immunology , 2013, 190: 000–000. to binding of the chemokine to HS chains on syndecan-3/syndecan-4, CXCR1, CXCR2, and DARC. ( ) Upon CXCL8 binding to the receptors, there are changes in signaling pathways, reorganization of the cytoskeleton, and the formation of ﬁlopodial and microvillous protrusions. Filopodial protrusions are long, laterally extending structures that can merge to form a mesh. On these structures, the chemokine is presented to leukocytes in the blood by HS on syndecan-3 and -4. Microvillous protrusions are shorter and more vertically orientated. They also present chemokines probably in association with HS (9).
Tier One Performance Screen Initial Operational Test and Evaluation: 2013 Annual Report

Abstract : In addition to educational, physical, and moral screens, the U.S. Army relies on the Armed Forces Qualification Test (AFQT), a composite score from the Armed Services Vocational Aptitude Battery (ASVAB), to select new Soldiers into the Army. Although the AFQT is useful for selecting new Soldiers, other personal attributes are important to Soldier performance and retention. Based on previous U.S. Army Research Institute (ARI) investigations, the Army selected one promising measure, the Tailored Adaptive Personality Assessment System (TAPAS), for an initial operational test and evaluation (IOT and E), beginning administration to applicants in 2009. Criterion data are being compiled at 6-month intervals from administrative records, schools for selected military occupational specialties (MOS), and Soldiers in units. This is the eighth in a series of planned evaluations of the TAPAS. Similar to prior research, the cumulative results thus far suggest that several TAPAS scales significantly predict a number of criteria of interest, indicating that the measure holds promise for both selection and classification purposes.
(2018). Altimetry, gravimetry, GPS and viscoelastic modeling data for the joint inversion for glacial isostatic adjustment in Antarctica (ESA STSE Project REGINA). Earth System

The poorly known correction for the ongoing deformation of the solid Earth caused by glacial isostatic adjustment (GIA) is a major uncertainty in determining the mass balance of the Antarctic ice sheet from measurements of satellite gravimetry and to a lesser extent satellite altimetry. In the past decade, much progress has been made in consistently modeling ice sheet and solid Earth interactions; however, forward-modeling solutions of GIA in Antarctica remain uncertain due to the sparsity of constraints on the ice sheet evolution, as well as the Earth’s rheological properties. An alternative approach towards estimating GIA is the joint inversion of multiple satellite data – namely, satellite gravimetry, satellite altimetry and GPS, which reﬂect, with different sensitivities, trends in recent glacial changes and GIA. Crucial to the success of this approach is the accuracy of the space-geodetic data sets. Here, we present reprocessed rates of surface-ice elevation change (Envisat/Ice, Cloud,and land Elevation Satellite, ICESat; 2003–2009), gravity ﬁeld change (Gravity Recovery and Climate Experiment, GRACE; 2003–2009) and bedrock uplift (GPS; 1995–2013). The data analysis is complemented by the forward modeling of viscoelastic response functions to disc load forcing, allowing us to relate GIA-induced surface displacements with gravity changes for different rheological parameters of the solid Earth. The data and modeling results presented here are available in the PANGAEA database (https://doi.org/10.1594/PANGAEA.875745). The data sets are the input streams for the joint inversion estimate of present-day ice-mass change and GIA, focusing on Antarctica. However, the methods, code and data provided in this paper can be used to solve other problems, such as volume balances of the Antarctic ice sheet, or can be applied to other geographical regions in Published by Copernicus Publications. the case of the viscoelastic response functions. This paper presents the ﬁrst of two contributions summarizing the work carried out within a European Space Agency funded study: Regional glacial isostatic adjustment and CryoSat elevation rate corrections in Antarctica (REGINA).
Priming of Protective Anti- Listeria monocytogenes Memory CD8 (cid:1) T Cells Requires a Functional SecA2 Secretion System (cid:1)

The SecA2 auxiliary secretion system of Gram-positive bacteria promotes the export of virulence proteins essential for colonization of the host in the case of both Mycobacterium tuberculosis and Listeria monocytogenes , two intracellular bacteria causing diseases in humans. We and others have demonstrated that this secretion system is also linked to the onset of long-term CD8 (cid:1) T cell-mediated protective immunity in mice. In the case of L. monocytogenes , expression of SecA2 inside the cytosol of infected cells correlates with the generation of CCL3-secreting memory CD8 (cid:1) T cells that are required for protection against secondary challenge with wild-type (wt) L. monocytogenes. Since the SecA2 ATPase is well conserved among Gram-positive pathogenic bacteria, we hypothesized that SecA2 itself bears evolutionarily conserved motifs recognized by cytosolic to with a horseradish peroxidase (HRP)-coupled anti-FLAG monoclonal antibody (MAb) (clone M2; Sigma), and (Chemiglow substrate) using FluorChem FC2 imaging system (Alpha Innotech). Quan- tiﬁcation was performed with AlphaView software.
OTT_A_253137 7629..7639

Bing Liu* Meiyue Song* Huadong Qin Bin Zhang Yao Liu Yu Sun Yanfei Ma Tiefeng Shi 1 1The 4th Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin City 150086, Heilongjiang Province, People’s Republic of China; 2The Pathology Department, The Second Affiliated Hospital of Harbin Medical University, Harbin City 150086, Heilongjiang Province, People’s Republic of China
rapid communication Voltage-independent changes in L-type Ca 2 1 current uncoupled from SR Ca 2 1 release in cardiac myocytes

and D. Stern. Voltage-independent changes in L-type Ca 2 1 current uncoupled from SR Ca 2 1 release in cardiac myocytes. Am J Physiol Heart Circ Physiol 279: H2024–H2031, 2000. —To determine the effect of voltage-independent alterations of L-type Ca 2 1 current ( I Ca ) on the sarcoplasmic reticular (SR) Ca 2 1 release in cardiac myocytes, we measured I Ca and cytosolic Ca 2 1 transients (Ca i2 1 ; intracellular Ca 2 1 concentration) in voltage-clamped rat ventricular myocytes during 1 ) an abrupt increase of extracellular [Ca 2 1 ] (Ca o2 1 ) or 2 ) application of 1 m M FPL-64176, a Ca 2 1 channel agonist, to selectively alter I Ca in the absence of changes in SR Ca 2 1 loading. On the ﬁrst depolarization in higher Ca o2 1 , peak I Ca was increased by 46 6 6% ( P , 0.001), but the increases in the maximal rate of rise of Ca i2 1 (dCa i2 1 /d t max , where t is time; an index of SR Ca 2 1 release ﬂux) and the Ca i2 1 transient amplitude were not signiﬁcant. Rapid exposure to FPL-64176 greatly slowed inactivation of I Ca , increasing its time integral by 117 6 8% ( P , 0.001) without signiﬁcantly increasing peak I Ca , dCa i2 1 / d t max , or amplitude of the corresponding Ca i2 1 transient. Prolongation of exposure to higher Ca o2 1 or FPL-64176 did not further increase peak I Ca but greatly increased dCa i2 1 / d t max , Ca i2 1 transient amplitude, and the gain of Ca 2 1 release (dCa i2 1 /d t max / I Ca ), evidently due to augmentation of the SR Ca 2 1 loading. Also, the time to peak dCa i 2 1 /d t max was signiﬁcantly increased in the continuous presence of higher Ca o2 1 (by 37 6 5%, P , 0.001) or FPL-64176 (by 63 6 5%, P , 0.002). Our experiments provide the ﬁrst evidence of a marked disparity between an increased peak I Ca and the corresponding SR Ca 2 1 release. We attribute this to saturation of the SR Ca 2 1 release ﬂux as predicted by local control theory. Prolongation of the SR Ca 2 1 release ﬂux, caused by combined actions of a larger I Ca and maximally augmented SR Ca 2 1 loading, might reﬂect additional Ca 2 1 release from corbular SR.
Binaural weighting of pinna cues in human sound localization

Human sound localization relies on binaural difference cues for sound-source azimuth and pinnarelated spectral shape cues for sound elevation. Although the interaural timing and level difference cues are weighted to produce a percept of sound azimuth, much less is known about binaural mechanisms underlying elevation perception. This problem is particularly interesting for the frontal hemifield, where binaural inputs are of comparable strength. In this paper, localization experiments are described in which hearing for each ear was either normal, or spectrally disrupted by a mold fitted to the external ear. Head-fixed saccadic eye movements were used as a rapid and accurate indicator of perceived sound direction in azimuth and elevation. In the control condition (both ears free) azimuth and elevation components of saccadic responses were well described by a linear regression line for the entire measured range. For unilateral mold conditions, the azimuth response components did not differ from controls. The influence of the mold on elevation responses was largest on the ipsilateral side, and declined systematically with azimuth towards the side of the free ear. Near the midsagittal plane the elevation responses were clearly affected by the mold, suggesting a systematic binaural interaction in the neural computation of perceived elevation that straddles the midline. A quantitative comparison of responses from the unilateral mold, the bilateral mold and control condition provided evidence that the fusion process can be described by binaural weighted averaging. Two different conceptual schemes are discussed that could underlie the observed responses.
T H E K I N E T I C S OF CARDIAC GLYCOSIDE I N H I B I T I O N OF POTASSIUM TRANSPORT I N HUMAN ERYTHROCYTES*

The present study of the kinetics of the inhibition of K transport in glycosidepoisoned human red cells has been undertaken in an effort to throw more light on the detailed mechanism by which K enters the normal cell. In 1953, Schatzmann (1) reported that cardiac glycosides inhibitied in a marked manner the uptake of K at 37°C. by red cells which had been depleted of intracelluiar K by cold storage. Since then Schatzmann's studies have been confirmed and extended by Joyce and Weatherall (2), Glynn (3), and Kahn and Acheson (4). The specific aspects of the problem that have been explored in the present study are: the development of the necessary kinetic treatment to cover the behavior of a heterogeneous three compartment system that is not in the steady state; the provision of a theory to account for the quantitative relationship between glycoside concentration and its effect on K transport; and a comparison of the glycoside--red cell dissociation constants with the mean lethal dose of the glycoside in the cat.