Miracle-dz/UniFAR-FTUs huggingface dataset:
Cytological and molecular diagnosis of Hürthle cell thyroid tumors: Analysis of three cases

The cytological diagnosis of Hürthle cell (oncocytic) thyroid tumors by means of fine-needle aspiration biopsy represents a challenge, as Hürthle cell polymorphism and atypia alone are not indications of malignancy. In our recent work, an original diagnostic algorithm was proposed, which identified and typed malignant thyroid tumors by analyzing the molecular markers of cytological preparations. The aim of the present study was to assess the effectiveness of this algorithm at detecting Hürthle cell thyroid tumors in clinical samples used for cytological examination. Cytological and histological examinations of the biopsy material were performed for three patients with nodular neoplasms. Biopsy material of these patients was analyzed by quantitative PCR using preselected molecular markers [normalized concentrations of High-mobility group AT-hook 2 mRNA, three microRNAs (miRNAs or miRs; miR-146b, miR-221 and miR-375) and the mitochondrial (mtDNA)/nuclear DNA ratio]. The results revealed that the molecular test determined the malignancy of three cases of Hürthle cell tumor. This method may therefore be used to complement the cytological diagnosis of fine-needle aspiration biopsy. In all three cases, there was an increased content of mtDNA, indicating Hürthle cell malignancies. Furthermore, in the first case [Hürthle cell carcinoma (HCC)], increased miRNA-221 content was detected, which also indicated malignancy. In the second case (Hürthle cell papillary thyroid carcinoma), an increased level of miRNA-146b was present, which indicated papillary carcinoma. In the third case (Hürthle cell adenoma), no markers of malignancy were identified. The present study demonstrated that molecular testing together with cytological analysis can reduce the isk of error in the preoperative cytological diagnosis of unclear or ambivalent cases.
Spatial Analysis of Ambient Air Pollution and Cardiovascular Disease (CVD) Hospitalization Across Sweden

The associations of multiple pollutants and cardiovascular disease (CVD) morbidity, and the spatial variations of these associations have not been nationally studied in Sweden. The main aim of this study was, thus, to spatially analyze the associations between ambient air pollution (black carbon, carbon monoxide, particulate matter (both <10 µm and <2.5 µm in diameter) and Sulfur oxides considered) and CVD admissions while controlling for neighborhood deprivation across Sweden from 2005 to 2010. Annual emission estimates across Sweden along with admission records for coronary heart disease, ischemic stroke, atherosclerotic and aortic disease were obtained and aggregated at Small Areas for Market Statistics level. Global associations were analyzed using global Poisson regression and spatially autoregressive Poisson regression models. Spatial non‐stationarity of the associations was analyzed using Geographically Weighted Poisson Regression. Generally, weak but significant associations were observed between most of the air pollutants and CVD admissions. These associations were non‐homogeneous, with more variability in the southern parts of Sweden. Our study demonstrates significant spatially varying associations between ambient air pollution and CVD admissions across Sweden and provides an empirical basis for developing healthcare policies and intervention strategies with more emphasis on local impacts of ambient air pollution on CVD outcomes in Sweden.
Building a Robust QA system

Researchers today prioritize their time by building increasingly complex models that are harder to interpret and debug. The goal of this project is for us to discover how noninvasive techniques can be equally as effective. Namely, we explore how accuracy improves with hyperparameter tuning, various different methods of learning rate decay, and layer freezing. We also analyze the effects of data-side aug-mentations such as backtranslation, synonyms, masked learning, and upsampling. The last area of exploration is an altered loss function that biases against length. Our results indicate that layer-wise fine-tuning and data augmentation each lead to better accuracy and generalization, and the new loss function leads to predictions closer in length to the ground truth response length.
Effect of different rates of poultry droppings and plant spacing on soil chemical properties and yield of Cucumber

The effect of three different rates of poultry droppings (0kg/ha, 12kg/ha, 24kg/ha) and plant spacing (30cm x 50cm; 40cm x 50cm; 50cm x 50cm) and the soil chemical properties and yield of cucumber was studied in a field trial at Igbariam south eastern, Nigeria. The experiment was conducted as a 3x3 factorial laid out in randomized complete block design (RCBD) with two replications. The result of the study showed that poultry droppings and plant spacing significantly (p=0.05) increased the growth and yield of cucumber and improved the soil chemical parameters assessed. The values obtained increased as the rate of poultry droppings increased from zero level and decreased as the planting distance increased. The closest plant spacing (30cm x 50cm) and poultry droppings at the rate of 24kg/ha recorded the highest value in both crop and soil parameters assessed in this trial. Though the result of Mg 2+ showed a decrease as the rate of poultry droppings increased and Ca 2t result did not follow any particular trend. The spacing and poultry droppings interaction was significant for fruit yield (Weight of fruit), length of fruit and vine length, but generally showed non-significant for all the soil parameters measured. The result of the study showed that cucumber production could be enhanced at 24kg/ha poultry droppings and at a closer plant spacing of 30cm x 50cm for optimum yield. © 2014 Elixir All rights reserved ARTICLE INF O Articl e h istory: Received: 1 March 2014; Received in revised form: 20 April 2014; Accepted: 3 May 2014;
Genetic Diversity analysis in five accessions of Trigonella based on Seed protein Electrophoresis and RAPD

Biochemical and molecular characterization of five Trigonella accessions were carried out based on seed storage protein electrophoresis and RAPD marker. The electrophoretic pattern of proteins produced 3 monomorphic bands and 23 polymorphic bands and 7 species specific bands. RAPD results revealed high level of polymorphism among the studied genotypes. The primer OPP-02 produced reproducible polymorphic bands. A total of 19 amplified bands were generated across the studied accessions. 16 bands out of total number were polymorphic and 7 were unique. UPGMA dendrogram based Jacquard’s similarity matrix grouped all the accessions into two clusters. Based upon similarity matrix accessions A4 and A2 were close. On the other hand UPGMA dendrogram generated on the basis of jaccard ’ s similarity matrix revealed that accessions A1 and A2 Were very close to each other. No significant correlation was observed among the two marker systems utilized. It is concluded that Seed protein profiles could be useful, but RAPD profiles are reliable tools in the genetic diversity studies and genotype classification which can be used to improve the efficiency of Trigonella breeding programme. © 2015 Elixir All rights reserved ARTICLE INF O Articl e h istory: Received: 17 May 2013; Received in revised form: 11 January 2015; Accepted: 23 January 2015;
Building a Robust QA System that Knows When it Doesn’t Know

Machine Learning models have a hard time knowing when they shouldn’t be confident about their output. They falter when they see data that is out of their training distribution. Unfortunately, they falter in a way that the scores don’t properly reflect. For example, an MNIST model is capable of predicting a chicken is actually the number 5 with 99% certainty. While models are capable of generalizing to data they haven’t seen, they have a hard time knowing what data they can and can’t generalize to. A robust QA module should not only be able to do a good job of handling data it wasn’t modeled to handle, it should also be able to do a good job of knowing what data it can’t handle. The goal of our project is to initially build a good Question Answering model with an architecture that relies on a base of DistilBERT, improve on it through model fine-tuning, better optimization, and then augment the predictions of the model with a confidence score that is high when the model is reliable and low when the model is basically guessing on data it hasn’t seen.
The Mental Representation of Universal Quantifiers 1 The Mental Representation of Universal Quantifiers

A sentence like every circle is blue might be understood in terms of individuals and their properties (e.g., for each thing that is a circle, it is blue) or in terms of a relation between groups (e.g., the blue things include the circles). Relatedly, theorists can specify the contents of universally quantified sentences in first-order or second-order terms. We offer new evidence that this logical first-order vs. second-order distinction corresponds to a psychologically robust individual vs. group distinction that has behavioral repercussions. Participants were shown displays of dots and asked to evaluate sentences with each, every, or all combined with a predicate (e.g., big dot). We find that participants are better at estimating how many things the predicate applied to after evaluating sentences in which universal quantification is indicated with every or all, as opposed to each. We argue that every and all are understood in second-order terms that encourage group representation, while each is understood in first-order terms that encourage individual representation. Since the sentences that participants evaluate are truth-conditionally equivalent, our results also bear on questions concerning how meanings are related to truth-conditions.
PII: S0925-4773(99)00283-X

The organizer in vertebrate embryos has been shown to play a central role in their development by antagonizing ventralizing signals and promoting dorsal development. The ventral homeobox gene, Xvex-1, is capable of ful®lling some of the functions of BMP-4. By fusion to activation and repression domains, Xvex-1 was shown to function as a repressor of transcription. The activator version of Xvex-1, the antimorph, was made inducible by fusion to the ligand binding domain of the glucocorticoid receptor. The organizer genes, gsc and Otx-2, were identi®ed as direct targets of Xvex-1. The XVEX-1 antimorph can induce the formation of secondary axes. Temporal analysis of secondary axis induction revealed that the competence to induce a secondary organizer ends with the onset of gastrulation. The same temporal competence window was exhibited by an inducible gsc construct. Partial loss of Xvex-1 activity was able to improve the ef®ciency of secondary axis induction by the dominant negative BMP receptor or Smad6. These observations together with the early widespread expression of Xvex-1 throughout the embryo prior to gastrulation encoding a homeodomain repressor protein, suggest that elements of the ventral signaling pathway play an important role during late blastula in restricting the formation of Spemann's organizer. q 2000 Elsevier Science Ireland Ltd. All rights reserved.
Metallophthalocyanine derivatives utilized as cathode interlayers for polymer solar cells: a practical approach to prepare a uniform film

Three metallophthalocyanine derivatives: 2,3,9,10,16,17,23,24-octakis-[N-ethyl-(3-pyridyloxy)]vanadylphthalocyanine bromine (1 : 8) (VOPc(OPyC2H5Br)8), 2,3,9,10,16,17,23,24-octakis-[N-butyl-(3-pyridyloxy)]vanadylphthalocyanine bromine (1 : 8) (VOPc(OPyC4H9Br)8) and 2,3,9,10,16,17,23,24-octakis-[N-hexyl-(3-pyridyloxy)]vanadylphthalocyanine bromine (1 : 8) (VOPc(OPyC6H13Br)8) were synthesized and applied in polymer solar cells (PSCs) based on PTB7:PC71BM (PTB7 = thieno[3,4-b]thiophene/benzodithiophene, PC71BM = [6,6]-phenyl C71-butyric acidmethyl ester) as an active layer. As a result, the highest power conversion efficiency (PCE) value of the PSCs is 7.99% for the device with VOPc(OPyC2H5Br)8 as a cathode interlayer. Although increasing the alkyl side chains attached to the pyridine functional groups of phthalocyanine leads to a slight decrease of PCE, VOPc(OPyC6H13Br)8 can form a better, denser and more uniform film on the active layer as demonstrated by atomic force microscopy, energy dispersive spectrum mapping and contact angle measurements.
Endophytes isolated from Panax notoginseng converted ginsenosides

Endophytes may participate in the conversion of metabolites within medicinal plants, influencing the efficacy of host. However, the distribution of endophytes within medicinal plants P. notoginseng and how it contributes to the conversion of saponins are not well understood. Here, we determined the distribution of saponins and endophytes within P. notoginseng compartments and further confirm the saponin conversion by endophytes. We found metabolites showed compartment specificity within P. notoginseng. Potential saponin biomarkers, such as Rb1, Rg1, Re, Rc and Rd, were obtained. Endophytic diversity, composition and co‐occurrence networks also showed compartment specificity, and bacterial alpha diversity values were highest in root compartment, consistently decreased in the stem and leaf compartments, whereas those of fungi showed the opposite trend. Potential bacterial biomarkers, such as Rhizobium, Bacillus, Pseudomonas, Enterobacter, Klebsiella, Pantoea and fungal biomarkers Phoma, Epicoccum, Xylariales, were also obtained. Endophytes related to saponin contents were found by Spearman correlation analysis, and further verification experiments showed that Enterobacter chengduensis could convert ginsenoside Rg1 to F1 at a rate of 13.24%; Trichoderma koningii could convert ginsenoside Rb1 to Rd at a rate of 40.00% and to Rg3 at a rate of 32.31%; Penicillium chermesinum could convert ginsenoside Rb1 to Rd at a rate of 74.24%.
‘More than biological’: Cherie Dimaline’s The Marrow Thieves as Indigenous countergenetic fiction

This article reads Métis writer Cherie Dimaline’s novel The Marrow Thieves as one among a growing number of Indigenous countergenetic fictions. Dimaline targets two initiatives that reductively define indigeneity as residing in so-called Native American DNA: (1) direct-to-consumer genetic testing, through which an increasing number of people lay dubious claim to Indigenous ancestry, and (2) population genetics projects that seek urgently to sample Indigenous genetic diversity before Indigenous Peoples become too admixed and therefore extinct. Dimaline unabashedly incorporates the terminology of genetics into her novel, but I argue that she does so in order ultimately to underscore that genetics is ill-equipped to understand Indigenous ways of articulating kinship and belonging. The novel carefully articulates the full complexity of Indigenous self-recognition practices, urging us to wrestle with the importance of both the biological (DNA, blood and relation) and the ‘more than biological’ (story, memory, reciprocal ties of obligation and language) for Indigenous self-recognition and continuity. The novel shows that,to grasp Indigenous modes of self-recognition is to understand that Indigenous belonging exceeds any superficial sense of connection that a DNA test may produce and that, contrary to population geneticists’ claims, Indigenous Peoples are not vanishing but instead are actively engaged in everyday practices of survival. Finally, I point out that Dimaline—who identifies as Two-Spirit—does not idealise Indigenous communities and their ways of recognising their own; The Marrow Thieves also explicitly gestures to the ways in which Indigenous kinship-making practices themselves need to be rethought in order to be more inclusive of queer Indigenous Peoples.
Estimation of age at onset of linear enamel hypoplasia. New calculation tool, description and comparison of current methods

Enamel Hypoplasia (EH) is known to be a useful indicator for wide range of detrimental factors in early childhood in past populations, such as nutritional disturbances, mechanical trauma, disease, metabolic, and/or genetic disorders. EH may be divided into three categories: pits, grooves, and lines, where the last two are referred to as “Linear Enamel Hypoplasia” (LEH). The regularity of enamel formation allows retrospective determination of the age of LEH formation. The current article reviews and compares the best‐known methods used to estimate age at LEH formation and provides a new computational tool. Growth curves for canines and incisors were developed based on tooth growth tables by previous authors. Optimal models were selected using the Akaike Information Criterion. A Microsoft Excel spreadsheet was created to calculate age at LEH formation using the most common methods. All method results were compared with an archaeological sample (44 teeth of 18 individuals from an early modern cemetery from Wrocław, Poland) and a theoretical model. The results of the methods were compared pairwise with Bland‐Altman plots. The current article provides a quick and easy‐to‐use tool for analyzing LEH chronology and comparing the results of different methods. As shown by the Bland‐Altman plots, most methods provide approximately consistent results for LEHs formed at around 2–3 years of age. However, LEHs formed particularly early or late are more prone to discrepancies between different methods. Comparison of the age at LEH formation obtained by different methods should be done carefully ‐ and the new LEH calculation tool with optimized equations provided in this publication can facilitate this process.
Prognostic Value and Relation with Adjuvant Treatment Duration of ctDNA in Stage III Colon Cancer: a Post Hoc Analysis of the PRODIGE-GERCOR IDEA-France Trial

Purpose: Circulating tumor DNA (ctDNA) has been suggested as a major prognostic factor in resected stage-III colon cancer. We analyzed ctDNA of patients randomized in the phase III IDEA-France trial. Experimental Design: ctDNA was tested for WIF1 and NPY by droplet digital PCR with method developed and validated for colorectal cancer. Disease-free survival (DFS) and overall survival (OS) were analyzed via multivariable analysis in patients with ctDNA samples and in sub-groups according to treatment duration (3/6 months) and disease stage (high/low-risk stage III). Results: Of 2,010 randomized patients, 1,345 had available ctDNA samples (1,017 collected both post-surgery and pre-chemotherapy). More Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 (78% versus 69%) and T4 and/or N2 (40% versus 36%) were observed in patients studied (n = 1017) versus not analyzed (n = 993). There were 877 ctDNA-negative (86.2%) and 140 ctDNA-positive (13.8%) patients; their baseline characteristics were similar. With a median follow-up of 6.6 years, the 3-year DFS rate was 66.39% for ctDNA-positive patients and 76.71% for ctDNA-negative patients (P = 0.015). ctDNA was confirmed as an independent prognostic marker for DFS (adjusted HR = 1.55, 95% CI 1.13–2.12, P = 0.006) and OS (HR = 1.65, 95% CI 1.12–2.43, P = 0.011). ctDNA was prognostic in patients treated for 3 months and with T4 and/or N2 tumors, but not in those treated for 6 months and with T1–3/N1 tumors. Conclusions: In this first ctDNA assessment of a large series of patients with stage III colon cancer enrolled in phase III trial, post-surgery ctDNA was found in 13.8% of them and was confirmed as an independent prognostic marker. See related commentary by Bent and Kopetz, p. 5449
Development, validation and application of physiologically based biopharmaceutics model to justify the change in dissolution specifications for DRL ABC extended release tablets

Abstract Objective The generic drug product DRL ABC is an Extended Release (ER) Tablet manufactured by Dr. Reddy’s Laboratories Limited and have multi point dissolution as part of release specification. A proposal is being made to revise the dissolution specification and the aim of present work was to evaluate if this would still provide bioequivalent product. Methods PBBM was developed for DRL ABC using literature reported pharmacokinetic (PK) data. The intravenous PK data and in vitro metabolic rate constants were utilized for developing PBPK model first, followed by that in conjugation with mechanistic ACATTM model, a PBBM is developed for per-oral immediate release formulations. The validated model was applied to predict clinical bioequivalence (BE) study data for the Reference (Innovator ER Tablet) and Test product. For Reference and Test product, in vivo dissolution profiles were mechanistically deconvoluted from plasma concentration (Cp)-time profiles. Further, mechanistic in vitro-in vivo relationship (IVIVR) applied to in vitro release profiles of two hypothetical Test product batches (one with single point low dissolution profile (SPLP) and other with overall low dissolution profile (LP)) in order to calculate their in vivo releases and population simulation was performed with 40 virtual subjects. Results Results from the cross-over virtual trials showed BE between the Reference and various Test product batches (SPLP and LP), with maximum Cp (Cmax) and area under the Cp-time curve (AUC0-inf) well within 80-125% range. Conclusion PBBM in conjugation with IVIVR and virtual BE was successfully applied for justifying changes in dissolution specification of DRL ABC.
Native Mass Spectrometry and Gas-Phase Fragmentation Provide Rapid and In-Depth Topological Characterization of a PROTAC Ternary Complex

Proteolysis-targeting chimeras (PROTACs) represent a new direction in small-molecule therapeutics whereby a heterobifunctional linker to a protein of interest (POI) induces its ubiquitination-based proteolysis by recruiting an E3 ligase. Here, we show that charge reduction, native mass spectrometry, and gas-phase activation methods combine for an in-depth analysis of a PROTAC-linked ternary complex. Electron capture dissociation (ECD) of the intact POI-PROTAC-VCB complex (a trimeric subunit of an E3 ubiquitin ligase) promotes POI dissociation. Collision-induced dissociation (CID) causes elimination of the nonperipheral PROTAC, producing an intact VCB-POI complex not seen in solution but consistent with PROTAC-induced protein-protein interactions. In addition, we used ion mobility spectrometry (IMS) and collisional activation to identify the source of this unexpected dissociation. Together, the evidence shows that this integrated approach can be used to screen for ternary complex formation and PROTAC-protein contacts and may report on PROTAC-induced protein-protein interactions, a characteristic correlated with PROTAC selectivity and efficacy.