Miracle-dz/UniFAR-FTUs huggingface dataset:
Deep Learning with Permutation-invariant Operator for Multi-instance Histopathology Classification

The computer-aided analysis of medical scans is a longstanding goal in the medical imaging field. Currently, deep learning has became a dominant methodology for supporting pathologists and radiologist. Deep learning algorithms have been successfully applied to digital pathology and radiology, nevertheless, there are still practical issues that prevent these tools to be widely used in practice. The main obstacles are low number of available cases and large size of images (a.k.a. the small n, large p problem in machine learning), and a very limited access to annotation at a pixel level that can lead to severe overfitting and large computational requirements. We propose to handle these issues by introducing a framework that processes a medical image as a collection of small patches using a single, shared neural network. The final diagnosis is provided by combining scores of individual patches using a permutation-invariant operator (combination). In machine learning community such approach is called a multi-instance learning (MIL).
miR-146b is highly expressed in adult papillary thyroid carcinomas with high risk features including extrathyroidal invasion and the BRAF(V600E) mutation.

BACKGROUND Papillary thyroid carcinoma (PTC) are clinicopathogenetically heterogeneous. Micro-RNAs (miRNAs) are involved in the pathogenesis of diverse human cancers, including PTC. Information regarding associations between clinicopathological features of PTC with the expression of specific miRNAs, however, is sparse. In this study, we compared expression of deregulated miRNAs in PTCs to assess this was associated with selected clinicopathogenetic features. METHODS We analyzed the expression levels of three reported deregulated miRNAs (miR-221, miR-222, and miR-146b) using quantitative real-time polymerase chain reaction in 100 cases of PTCs with distinct clinicopathogenetic characteristics and 16 paired normal controls. The tumor samples were categorized into low- and high-risk groups on the basis of the tumor-node-metastasis staging system. RESULTS The expression levels of miR-221, miR-222, and miR-146b were significantly associated with extrathyroidal invasion (p = 0.013, 0.05, and 0.003, respectively). The expression levels of miR-221 and miR-146b were significantly higher in the high-risk PTC group (p = 0.01 and 0.042, respectively). The miR-146b expression levels in PTCs with BRAF mutation were significantly higher than those without this mutation (p < 0.0001). There were no other associations between the expression of these miRNAs and other clinicopathological parameters. CONCLUSIONS Our results show the potential importance of miR-221, miR-222, and miR-146b in determining the aggressive properties of PTCs and highlight the need to identify the gene targets of these miRNAs.
Identification of a new transcriptional unit that yields a gene product within the unique sequences of the short component of the herpes simplex virus 1 genome

The herpes simplex virus genome 1 consists of two unique stretches, long (UL) and short (U(S)), each flanked by inverted repeat sequences. The U(S) sequence has been previously reported to contain 12 open reading frames designated U(S)1 through U(S)12. This report demonstrates the existence of a 13th open reading frame within the U(S) sequence, designated U(S)8.5. The U(S)8.5 sequence is located between, and overlaps in part with, the domains of the U(S)8 and U(S)9 genes. Its transcription is initiated within the coding sequence of U(S)8, and its transcript decays earlier than that of U(S)8. On the basis of the size of its RNA (1.2 kb) and map position, it is likely that the U(S)8.5 transcript is 3' coterminal with the U(S)8 and U(S)9 mRNAs at the single polyadenylation signal which serves these genes. The nucleotide sequence of the U(S)8.5 open reading frame predicts that its product is a 151-amino-acid basic, hydrophilic polypeptide. To determine whether the U(S)8.5 encodes a protein, a sequence encoding 23 amino acids that contains an epitope reacting with a known monoclonal antibody to human cytomegalovirus protein was inserted in frame after the predicted fifth codon of the U(S)8.5 gene. The recombinant virus carrying this epitope induced the synthesis of a protein reactive with the monoclonal antibody in immunoblots. The tagged protein localized in nucleoli of cells infected with the recombinant virus.
Activation of phospholipase C in SH‐SY5Y neuroblastoma cells by potassium‐induced calcium entry

1 We used SH‐SY5Y human neuroblastoma cells to investigate whether depolarization with high K+ could stimulate inositol (1,4,5)trisphosphate (Ins(1,4,5)P3) formation and, if so, the mechanism involved 2 Ins(1,4,5)P3 was measured by a specific radioreceptor mass assay, whilst [Ca2+]i was measured fluorimetrically with the Ca2+ indicator dye, Fura‐2 3 Depolarization with K+ caused a time‐ and dose‐dependent increase in [Ca2+]j (peak at 27 s, EC50 of 50.0±9.0 mM) and Ins(1,4,5)P3 formation (peak at 30 s, EC50 of 47.4±1.1 mM) 4 Both the K+‐induced Ins(1,4,5)P3 formation and increase in [Ca2+]i were inhibited dose‐dependently by the L‐type voltage‐sensitive Ca2+ channel closer(R +)‐BayK8644, with IC50 values of 53.4 nM and 87.9 nM respectively. 5 These data show a close temporal and dose‐response relationship between Ca2+ entry via L‐type voltage‐sensitive Ca2+ channels and Ins(1,4,5)P3 formation following depolarization with K+, indicating that Ca2+ influx can activate phospholipase C in SH‐SY5Y cells
A discrete affinity-driven elevation of ZAP-70 kinase activity initiates negative selection

Context: Although ZAP-70 is required for T-cell development, it’s unclear how this kinase controls both positive and negative selection. Objective and methods: Using OT-I pre-selection thymocytes and a panel of peptide major histocompatibility complex (pMHC) ligands of defined affinity, the recruitment, phosphorylation and activity of ZAP-70 was determined at the interface with antigen-presenting cells (APCs). Results: pMHC ligands promoting negative selection induce a discrete elevation of ZAP-70 recruitment, phosphorylation and enzymatic activity in the thymocyte:APCs interface. Discussion: The quantity of ZAP-70 kinase activity per cell is a key parameter controlling the fate of a developing thymocyte since partial inhibition of ZAP-70 kinase activity converted negative into positive selection. Surprisingly, the amount of ZAP-70 enzymatic activity observed during negative selection is not controlled by differential phosphorylation of the ZAP-70 protein but rather by the total amount of T-cell receptor and co-associated ZAP-70 recruited to the thymocyte:APC interface. Conclusions: These data provide evidence that a burst of ZAP-70 activity initiates the signaling pathways for negative selection.
Chemical composition and antibacterial activity of leaves essential oil of Laurus nobilis from Morocco.

The extraction of essential oils of leaves of Laurus nobilis is obtained by hydrodistillation and analyzed by gas chromatography coupled with mass spectrometry (GC/MS) and gas chromatography with flame ionization detection (GC-FID) for determining their chemical composition and identification of their chemotypes. Their antibacterial activity was studied in vitro on tree bacterial strains: Staphylococcus aureus, Staphylococcus intermedius and Klebsiella pneumonia. The essential oil yields of the studies were 1.86%. The major component was 1,8-cineole (52.43%), other predominant components were a-terpinyl acetate (8.96%), sabinene (6.13%), Limonene (5.25%), a- pinene (3.72%), linalool (3.14%), terpinene-4-ol (2.56%), a-terpinene (2.12%), â-pinene (1.98%), a- terpineol (1.56%), bornyl acetate (1.89%), a-phellandrene (1.28%), myrcene (1.13%), camphene (1.05%), p-cymene (0.94%), o-terpinene (0.98%) and eugenol (0.56%). The chemical compositions revealed that this leaves had compositions similar to those of other Laurus nobilis essential oils analyzed in other countries. The bacterial strains tested were found to be sensitive to essential oils studied and showed a very effective bactericidal activity with minimum inhibitory concentrations (M IC) ranging from 0.01 to 1 mg/ ml.
Teledermatology research review

Teledermatology consultations can be performed using either store‐and‐forward or real‐time technology. The best‐studied aspect of teledermatology is diagnostic reliability, also known as diagnostic agreement. A good level of diagnostic reliability is achieved by dermatologists using both store‐and‐forward and real‐time modalities and is comparable to that found between clinic‐based examiners. Less information is available regarding diagnostic accuracy. Current data suggest that teledermatologists reviewing store‐and‐forward consults achieve accuracy comparable to that of clinic‐based dermatologists. When store‐and‐forward consult systems are used, approximately one in four in‐person clinic appointments are averted. Real‐time consult systems avoid the need to schedule approximately one in two clinic visits. Store‐and‐forward technology results in timelier interventions for patients when compared to a conventional referral process. To date, surveys of both store‐and‐forward and real‐time teledermatology consult modalities suggest that patients, referring clinicians, and dermatologists are all highly satisfied with teledermatology consults. Very little has been published about the economic impact of store‐and‐forward teledermatology, whereas several studies have evaluated real‐time modalities. Teledermatology has ranged from a cost‐saving strategy to an intervention that incurs greater costs than conventional care, depending on the health care setting and economic perspective. Future research focusing on diagnostic accuracy, clinical outcomes using clinical course or disease status as outcome measures, development of reliable and valid teledermatology‐specific survey instruments, and economic analyses that assess cost‐effectiveness will help guide future teledermatology program assessments and policy.
The Reliability of Multisource Feedback in Competency-Based Assessment Programs: The Effects of Multiple Occasions and Assessor Groups

Purpose Residency programs around the world use multisource feedback (MSF) to evaluate learners’ performance. Studies of the reliability of MSF show mixed results. This study aimed to identify the reliability of MSF as practiced across occasions with varying numbers of assessors from different professional groups (physicians and nonphysicians) and the effect on the reliability of the assessment for different competencies when completed by both groups. Method The authors collected data from 2008 to 2012 from electronically completed MSF questionnaires. In total, 428 residents completed 586 MSF occasions, and 5,020 assessors provided feedback. The authors used generalizability theory to analyze the reliability of MSF for multiple occasions, different competencies, and varying numbers of assessors and assessor groups across multiple occasions. Results A reliability coefficient of 0.800 can be achieved with two MSF occasions completed by at least 10 assessors per group or with three MSF occasions completed by 5 assessors per group. Nonphysicians’ scores for the “Scholar” and “Health advocate” competencies and physicians’ scores for the “Health advocate” competency had a negative effect on the composite reliability. Conclusions A feasible number of assessors per MSF occasion can reliably assess residents’ performance. Scores from a single occasion should be interpreted cautiously. However, every occasion can provide valuable feedback for learning. This research confirms that the (unique) characteristics of different assessor groups should be considered when interpreting MSF results. Reliability seems to be influenced by the included assessor groups and competencies. These findings will enhance the utility of MSF during residency training.
Online learning of the sensors fuzzy membership functions in autonomous mobile robots

We describe a technique which enables a fuzzy-logic based robot control system to automatically determine the membership functions (MF) of the input sensors online and in a short time interval. There is a necessity for such online self-calibration for fast changing and dynamic environments such as agricultural environments and difficult or inaccessible environments, such as nuclear reactors, underwater and space environments. In these media the robot has to learn the appropriate MF with no human intervention taking into account the difference in sensor characteristics in the different environments and changes in production requirements and repairing or otherwise upgrading robots. So there is a necessity to find a fast converging algorithm that can calibrate the MF online in real time with no need for human intervention or simulation. our work reports on an approach based on the use of a modified genetic algorithm to evolve the fuzzy MF of the individual behaviours. The MF of four behaviours were learnt online in an average time of 4 minutes for each behaviour in an outdoor environment. These learnt behaviours were then co-ordinated and tested in complex and dynamic environments in which the robot gave a very good response.
Anal and penile high-risk human papillomavirus prevalence in HIV-negative and HIV-infected MSM

Objective:Anal and penile high-risk human papillomavirus (HPV) infection is associated with anogenital cancer, which is especially common in HIV-infected MSM. We assessed HPV prevalence and determinants in MSM. Design:Analysis of baseline data from a prospective cohort study. Methods:MSM aged 18 years or older were recruited in Amsterdam, the Netherlands. Participants completed risk-factor questionnaires. HPV DNA was analyzed in anal and penile shaft self-swabs and genotyped using a sensitive PCR and reverse line blot assay (SPF10-PCR-DEIA-LiPA25-system). Multivariable logistic regression analyses were performed to assess determinants of high-risk HPV infection. Results:MSM (n = 778) were recruited in 2010–2011, of whom 317 (41%) were HIV-infected. Prevalence of anal high-risk HPV infection was 45% in HIV-negative versus 65% in HIV-infected MSM (P <0.001). HPV-16 was the most frequently detected type and was more common in HIV-infected MSM (13% in HIV-negative and 22% in HIV-infected MSM; P = 0.001). Prevalence of penile high-risk HPV infection was 16% in HIV-negative and 32% in HIV-infected MSM (P <0.001). In multivariable analyses, HIV infection remained associated with anal [adjusted odds ratio (aOR) 2.2; 1.8–2.7] and penile (aOR 2.0; 1.4–2.9) high-risk HPV infection. Higher number of lifetime male sex partners was significantly associated with anal and penile high-risk HPV in HIV-negative, but not HIV-infected MSM. Receptive anal intercourse was associated with anal high-risk HPV in HIV-infected MSM. Conclusion:Anal and penile high-risk HPV infections are very common in MSM. HIV infection is a strong and independent determinant for anal and penile high-risk HPV infection. Determinants for HPV infection appear to differ between HIV-negative and HIV-infected MSM.
Sodium glucose cotransporter SGLT1 as a therapeutic target in diabetes mellitus

ABSTRACT Introduction: Glycemic control is important in diabetes mellitus to minimize the progression of the disease and the risk of potentially devastating complications. Inhibition of the sodium–glucose cotransporter SGLT2 induces glucosuria and has been established as a new anti-hyperglycemic strategy. SGLT1 plays a distinct and complementing role to SGLT2 in glucose homeostasis and, therefore, SGLT1 inhibition may also have therapeutic potential. Areas covered: This review focuses on the physiology of SGLT1 in the small intestine and kidney and its pathophysiological role in diabetes. The therapeutic potential of SGLT1 inhibition, alone as well as in combination with SGLT2 inhibition, for anti-hyperglycemic therapy are discussed. Additionally, this review considers the effects on other SGLT1-expressing organs like the heart. Expert opinion: SGLT1 inhibition improves glucose homeostasis by reducing dietary glucose absorption in the intestine and by increasing the release of gastrointestinal incretins like glucagon-like peptide-1. SGLT1 inhibition has a small glucosuric effect in the normal kidney and this effect is increased in diabetes and during inhibition of SGLT2, which deliver more glucose to SGLT1 in late proximal tubule. In short-term studies, inhibition of SGLT1 and combined SGLT1/SGLT2 inhibition appeared to be safe. More data is needed on long-term safety and cardiovascular consequences of SGLT1 inhibition.
Characterization of duplicated zebrafish cyp19 genes.

The zebrafish has recently been developed as a good genetic model system. We report here the use of zebrafish to study the regulation of estrogen biosynthesis. The CYP19 gene encodes cytochrome P450 aromatase, which catalyzes the synthesis of estrogens. Two cyp19 genes, termed cyp19a and cyp19b, have been isolated from zebrafish. Sequence comparison shows that Cyp19a and Cyp19b belong to two separate Cyp19 subfamilies. The cyp19a gene is expressed in the ovary, whereas cyp19b is expressed in the brain. The cyp19a and cyp19b genes are located on zebrafish chromosomes LG 18 and 25, respectively. Our data indicate that these gene loci arose through an ancient chromosomal duplication event. The expression of duplicated genes in distinct tissues may have evolutionary significance.
Neutron structure of type‐III antifreeze protein allows the reconstruction of AFP–ice interface

Antifreeze proteins (AFPs) inhibit ice growth at sub‐zero temperatures. The prototypical type‐III AFPs have been extensively studied, notably by X‐ray crystallography, solid‐state and solution NMR, and mutagenesis, leading to the identification of a compound ice‐binding surface (IBS) composed of two adjacent ice‐binding sections, each which binds to particular lattice planes of ice crystals, poisoning their growth. This surface, including many hydrophobic and some hydrophilic residues, has been extensively used to model the interaction of AFP with ice. Experimentally observed water molecules facing the IBS have been used in an attempt to validate these models. However, these trials have been hindered by the limited capability of X‐ray crystallography to reliably identify all water molecules of the hydration layer. Due to the strong diffraction signal from both the oxygen and deuterium atoms, neutron diffraction provides a more effective way to determine the water molecule positions (as D2O). Here we report the successful structure determination at 293 K of fully perdeuterated type‐III AFP by joint X‐ray and neutron diffraction providing a very detailed description of the protein and its solvent structure. X‐ray data were collected to a resolution of 1.05 Å, and neutron Laue data to a resolution of 1.85 Å with a “radically small” crystal volume of 0.13 mm3. The identification of a tetrahedral water cluster in nuclear scattering density maps has allowed the reconstruction of the IBS‐bound ice crystal primary prismatic face. Analysis of the interactions between the IBS and the bound ice crystal primary prismatic face indicates the role of the hydrophobic residues, which are found to bind inside the holes of the ice surface, thus explaining the specificity of AFPs for ice versus water. Copyright © 2011 John Wiley & Sons, Ltd.
Revision Strategies of Student Writers and Experienced Adult Writers.

Although various aspects of the writing process have been studied extensively of late, research on revision has been notably absent. The reason for this, I suspect, is that current models of the writing process have directed attention away from revision. With few exceptions, these models are linear; they separate the writing process into discrete stages. Two representative models are Gordon Rohman's suggestion that the composing process moves from prewriting to writing to rewriting and James Britton's model of the writing process as a series of stages described in metaphors of linear growth, conception-incubation-production.1 What is striking about these theories of writing is that they model themselves on speech: Rohman defines the writer in a way that cannot distinguish him from a speaker ("A writer is a man who . puts [his] experience into words in his own mind"-p. 15); and Britton bases his theory of writing on what he calls (following Jakobson) the "expressiveness" of speech.2 Moreover, Britton's study itself follows the "linear model" of the relation of thought and language in speech proposed by Vygotsky, a relationship embodied in the linear movement "from the motive which engenders a thought to the shaping of the thought, first in inner speech, then in meanings of words, and finally in words" (quoted in Britton, p. 40). What this movement fails to take into account in its linear structure"first . then . finally"-is the recursive shaping of thought by language; what it fails to take into account is revision. In these linear conceptions of the writing process revision is understood as a separate stage at the end of the process-a stage that comes after the completion of a first or second draft and one that is temporally distinct from the prewriting and writing stages of the process.3 The linear model bases itself on speech in two specific ways. First of all, it is based on traditional rhetorical models, models that were created to serve the spoken art of oratory. In whatever ways the parts of classical rhetoric are
Use of metal-enhanced fluorescence spectroscopy for detection of polycyclic aromatic hydrocarbons in diesel oil emulsions in artificial seawater

In this study, we employed the metal-enhanced fluorescence (MEF) method for the detection of polycyclic aromatic hydrocarbons (PAHs) in diesel oil emulsions in artificial seawater. Silver nanoparticles with an average diameter of 80 nm were immobilized onto silanized quartz as MEF substrates. Excited by illumination at 355 nm, a 4.6-fold increase in the fluorescence signals of PAHs was recorded when MEF substrates were used. The finite-difference time-domain (FDTD) method was used to provide mechanistic insights into the fluorescence enhancement. Monitoring water pollution has environmental significance and MEF spectroscopy is finding direct applications in this field.
Modelling and mitigation of Flash Crashes September 2017

The algorithmic trading revolution has had a dramatic effect upon markets. Trading has become faster, and in some ways more efficient, though potentially at the cost higher volatility and increased uncertainty. Stories of predatory trading and flash crashes constitute a new financial reality. Worryingly, highly capitalised stocks may be particularly vulnerable to flash crashes. Amid fears of high-risk technology failures in the global financial system we develop a model for flash crashes. Though associated with extreme forms of illiquidity and market concentration flash crashes appear to be unpredictable in advance. Several measures may mitigate flash crash risk such as reducing the market impact of individual trades and limiting the profitability of high-frequency and predatory trading strategies. JEL Classification: C1 F3 G1 K2
Temperament and Developmental Pathways to Conduct Problems

This article reviews research linking a number of temperamental vulnerabilities to the development of severe conduct problems in children. Also reviewed are 2 areas of research that focus on important developmental processes that could mediate the relation between temperament and conduct problems. These processes are the development of emotional regulatory abilities and the development of the affective components of conscience. Both of these processes have been associated with certain temperamental vulnerabilities, and they can both place a child at risk for the development of conduct problems. Importantly, these 2 processes may designate children who develop conduct problems through distinct causal pathways and, as a result, could help to explain some of the subtypes of antisocial youth reported in past research.