Miracle-dz/UniFAR-FTUs huggingface dataset:
Use and Misuse of Triptans in France: Data from the Grim2000 Population Survey

The extent and nature of triptan use for headache relief has been evaluated in a large epidemiological survey in the French general population. Over 25 000 individuals were screened for headache and for triptan use. Of this sample, 290 triptan users were identified from whom extensive data on headache characteristics and healthcare resource consumption were obtained. The use of triptans is relatively infrequent, 0.2% in the general population, with only 7.5% of migraine sufferers using these drugs. The majority of triptan users were female (80%) and presented headache characteristics typical of migraine (80%). The remaining 20% of subjects were thus using triptans for headache types in which the utility of these drugs has not been demonstrated. Among migraineurs, triptan consumers reported more frequent and severe headaches than non-consumers, and reported a higher incidence of nausea and vomiting. The principal determinant of triptan prescription was consultation with a general practitioner (GP), which may itself have been triggered by the severity of the headaches. GPs, rather than specialists, are the primary prescribers of triptans in France.
Pulmonary oedema fluid induces non‐α‐ENaC‐dependent Na+ transport and fluid absorption in the distal lung

To determine if pulmonary oedema fluid (EF) alters ion and fluid transport of distal lung epithelium (DLE), EF was collected from rats in acute heart failure. EF, but not plasma, increased amiloride‐insensitive short circuit current (Isc) and Na+‐K+ ATPase protein content and pump activity of DLE grown in primary culture. Inhibitors of Cl− transport or cGMP‐gated cation channels had a significant (P < 0.05), but limited ability to block the increased Isc. EF increased amiloride‐insensitive, but not amiloride‐sensitive, DLE apical membrane Na+ conductance. The level of mRNA encoding epithelial sodium channel (ENaC) subunits was unchanged (α, β), or decreased (γ, P < 0.05) in EF‐exposed DLE. EF also induced an amiloride‐insensitive increase in the potential difference across murine tracheal cysts. Distal lung explants from late gestation wild‐type and α‐ENaC‐deficient fetal mice, which normally expand due to liquid secretion, decreased in size due to liquid absorption when exposed to EF. Trypsin digestion or heat treatment of EF abrogated the ability of EF to increase amiloride‐insensitive Isc in DLE and liquid absorption by distal lung explants. Thus proteins or protein‐dependent factors within cardiogenic EF induce an α‐ENaC‐independent and amiloride‐insensitive apical membrane Na+ conductance and liquid absorption in the distal lung.
Characterization of virus-like particles produced by the expression of rotavirus capsid proteins in insect cells

Rotaviruses are triple-layered particles that contain four major capsid proteins, VP2, VP4, VP6, and VP7, and two minor proteins, VP1 and VP3. We have cloned each of the rotavirus genes coding for a major capsid protein into the baculovirus expression system and expressed each protein in insect cells. Coexpression of different combinations of the rotavirus major structural proteins resulted in the formation of stable virus-like particles (VLPs). The coexpression of VP2 and VP6 alone or with VP4 resulted in the production of VP2/6 or VP2/4/6 VLPs, which were similar to double-layered rotavirus particles. Coexpression of VP2, VP6, and VP7, with or without VP4, produced triple-layered VP2/6/7 or VP2/4/6/7 VLPs, which were similar to native infectious rotavirus particles. The VLPs maintained the structural and functional characteristics of native particles, as determined by electron microscopic examination of the particles, the presence of nonneutralizing and neutralizing epitopes on VP4 and VP7, and hemagglutination activity of the VP2/4/6/7 VLPs. The production of VP2/4/6 particles indicated that VP4 interacts with VP6. Cell binding assays performed with each of the VLPs indicated that VP4 is the viral attachment protein. Chimeric particles containing VP7 from two different G serotypes also were obtained. The ability to express individual proteins or to coexpress different subsets of proteins provides a system with which to examine the interactions of the rotavirus structural proteins, the role of individual proteins in virus morphogenesis, and the feasibility of a subunit vaccine.
Big Self-Supervised Models are Strong Semi-Supervised Learners

One paradigm for learning from few labeled examples while making best use of a large amount of unlabeled data is unsupervised pretraining followed by supervised fine-tuning. Although this paradigm uses unlabeled data in a task-agnostic way, in contrast to most previous approaches to semi-supervised learning for computer vision, we show that it is surprisingly effective for semi-supervised learning on ImageNet. A key ingredient of our approach is the use of a big (deep and wide) network during pretraining and fine-tuning. We find that, the fewer the labels, the more this approach (task-agnostic use of unlabeled data) benefits from a bigger network. After fine-tuning, the big network can be further improved and distilled into a much smaller one with little loss in classification accuracy by using the unlabeled examples for a second time, but in a task-specific way. The proposed semi-supervised learning algorithm can be summarized in three steps: unsupervised pretraining of a big ResNet model using SimCLRv2 (a modification of SimCLR), supervised fine-tuning on a few labeled examples, and distillation with unlabeled examples for refining and transferring the task-specific knowledge. This procedure achieves 73.9\% ImageNet top-1 accuracy with just 1\% of the labels ($\le$13 labeled images per class) using ResNet-50, a $10\times$ improvement in label efficiency over the previous state-of-the-art. With 10\% of labels, ResNet-50 trained with our method achieves 77.5\% top-1 accuracy, outperforming standard supervised training with all of the labels.
Unsupervised Learning of Visual Features by Contrasting Cluster Assignments

Unsupervised image representations have significantly reduced the gap with supervised pretraining, notably with the recent achievements of contrastive learning methods. These contrastive methods typically work online and rely on a large number of explicit pairwise feature comparisons, which is computationally challenging. In this paper, we propose an online algorithm, SwAV, that takes advantage of contrastive methods without requiring to compute pairwise comparisons. Specifically, our method simultaneously clusters the data while enforcing consistency between cluster assignments produced for different augmentations (or views) of the same image, instead of comparing features directly as in contrastive learning. Simply put, we use a swapped prediction mechanism where we predict the cluster assignment of a view from the representation of another view. Our method can be trained with large and small batches and can scale to unlimited amounts of data. Compared to previous contrastive methods, our method is more memory efficient since it does not require a large memory bank or a special momentum network. In addition, we also propose a new data augmentation strategy, multi-crop, that uses a mix of views with different resolutions in place of two full-resolution views, without increasing the memory or compute requirements much. We validate our findings by achieving 75.3% top-1 accuracy on ImageNet with ResNet-50, as well as surpassing supervised pretraining on all the considered transfer tasks.
Wallerian degeneration of rat sciatic nerve. Changes in cholesteryl ester content and fatty acid composition

THE DIFFICULTY of studying demyelination processes in human disease necessitates the use of accessible and controllable animal models. Sciatic nerve undergoing Wallerian degeneration after unilateral section has often been used as such a model. A remarkable feature of demyelination is the appearance of cholesteryl esters. though their origin and function remain obscure. Some attention has been paid to their fatty acid composition in the hope that it might provide a clue to their metabolic role. Previous workers have stressed the similarity between the fatty acid composition of the cholesteryl esters in different human demyelinating diseases (ETO & SUZUKI, 1971) and also the generally similar pattern of cholesteryl ester fatty acids in a number of demyelinating disorders in animals (SWEASEY & PAITERSON, 1973) and in peripheral nerve after section
Generalising Recursive Neural Models by Tensor Decomposition

Most machine learning models for structured data encode the structural knowledge of a node by leveraging simple aggregation functions (in neural models, typically a weighted sum) of the information in the node’s neighbourhood. Nevertheless, the choice of simple context aggregation functions, such as the sum, can be widely sub-optimal. In this work we introduce a general approach to model aggregation of structural context leveraging a tensor-based formulation. We show how the exponential growth in the size of the parameter space can be controlled through an approximation based on the Tucker tensor decomposition. This approximation allows limiting the parameters space size, decoupling it from its strict relation with the size of the hidden encoding space. By this means, we can effectively regulate the trade-off between expressivity of the encoding, controlled by the hidden size, computational complexity and model generalisation, influenced by parameterisation. Finally, we introduce a new Tensorial Tree-LSTM derived as an instance of our framework and we use it to experimentally assess our working hypotheses on tree classification scenarios.
Metabolic Syndrome in Elderly Living in Marginal Peri‐Urban Communities in Quito, Ecuador

The number of the elderly in Latin America is expected to double in the next few decades. Metabolic syndrome (MetS) is associated with high morbidity and mortality. However, little is known about MetS in Latin America. The objective of this study was to examine the prevalence of MetS in a low income urban area, and to evaluate the association between blood micronutrient, homocysteine (tHcy) and CRP levels with MetS. We performed a cross‐sectional study of 352 elderly (≥ 65 years) Ecuadorians living in a peri‐urban slum community in Quito, Ecuador. MetS was prevalent (45%)—more so among women (53%) than men (29%). In addition, many of those without MetS exhibited one or more risk factors for MetS. Plasma micronutrient deficiencies were prevalent: >70% for vitamin C, >45% for Zinc, and >20% for vitamin B12 and folate. Vitamin C and E concentrations were inversely, and CRP positively associated with MetS. The co‐existence of MetS with micronutrient deficiencies indicates that elderly Ecuadorians suffer from the double burden of diseases associated with the nutrition transition in less‐developed countries. Research is needed to determine causal factors, but interventions to normalize blood lipids, reduce hypertension and weight gain, and to improve micronutrient status, appear to be needed in this population. Supported by NIH Fogarty International Center (1 R03 TW005779‐01A1), NIA (2R01 AG009140‐10A1), and USDA (Contract #58‐1950‐7‐707).
GJ 273: on the formation, dynamical evolution, and habitability of a planetary system hosted by an M dwarf at 3.75 parsec

Context. Planets orbiting low-mass stars such as M dwarfs are now considered a cornerstone in the search for planets with the potential to harbour life. GJ 273 is a planetary system orbiting an M dwarf only 3.75 pc away, which is composed of two confirmed planets, GJ 273b and GJ 273c, and two promising candidates, GJ 273d and GJ 273e. Planet GJ 273b resides in the habitable zone. Currently, due to a lack of observed planetary transits, only the minimum masses of the planets are known: Mb sin ib = 2.89 M⊕, Mc sin ic = 1.18 M⊕, Md sin id = 10.80 M⊕, and Me sin ie = 9.30 M⊕. Despite its interesting character, the GJ 273 planetary system has been poorly studied thus far. Aims. We aim to precisely determine the physical parameters of the individual planets, in particular, to break the mass–inclination degeneracy to accurately determine the mass of the planets. Moreover, we present a thorough characterisation of planet GJ 273b in terms of its potential habitability. Methods. First, we explored the planetary formation and hydration phases of GJ 273 during the first 100 Myr. Secondly, we analysed the stability of the system by considering both the two- and four-planet configurations. We then performed a comparative analysis between GJ 273 and the Solar System and we searched for regions in GJ 273 which may harbour minor bodies in stable orbits, that is, the main asteroid belt and Kuiper belt analogues. Results. From our set of dynamical studies, we find that the four-planet configuration of the system allows us to break the mass–inclination degeneracy. From our modelling results, the masses of the planets are unveiled as: 2.89 ≤ Mb ≤ 3.03 M⊕, 1.18 ≤ Mc ≤ 1.24 M⊕, 10.80 ≤ Md ≤ 11.35 M⊕, and 9.30 ≤ Me ≤ 9.70 M⊕. These results point to a system that is likely to be composed of an Earth-mass planet, a super-Earth and two mini-Neptunes. Based on planetary formation models, we determine that GJ 273b is likely an efficient water captor while GJ 273c is probably a dry planet. We find that the system may have several stable regions where minor bodies might reside. Collectively, these results are used to offer a comprehensive discussion about the habitability of GJ 273b.
Activation of Janus kinase 1 confers poor prognosis in patients with non-small cell lung cancer

The activation of Janus kinase 1 (JAK1) has been reported to occur in non-small cell lung cancer (NSCLC), activating the JAK/signal transducers and activators of transcription cascade. However, the association between JAK1 activation and the prognostic value in NSCLC remains unclear. The present study initially investigated the association between expression of the activated form of JAK1 (p-JAK1) and prognosis in patients with NSCLC. A cohort of 142 resected primary NSCLC tissue samples, including 74 adenocarcinoma (ADCC) and 68 squamous cell carcinoma samples, were analyzed. p-JAK1 expression status was determined by immunohistochemistry. Evaluation of epidermal growth factor receptor (EGFR) gene amplification by fluorescence in situ hybridization was subsequently performed in 74 ADCC samples. The prognostic significance of p-JAK1 expression and EGFR gene amplification were evaluated with univariate and multivariate survival analyses. Compared with normal lung tissue, p-JAK1 expression level was significantly increased in NSCLC (P<0.001). Positive p-JAK1 expression indicated a poor prognosis, particularly for patients in early stages (stage I/II, including tumor size <3 cm, Lymph node invasion N0/1; all P<0.05). p-JAK1 expression was an independent predictor of a poor prognosis (P=0.022). The overall survival time for patients with positive p-JAK1 expression and EGFR-amplified tumors was significantly shortened compared with patients with tumors negative for one or both features (both features present vs. neither feature present, P<0.001). The results provided clinical evidence that the activation of JAK1 was an independent prognostic factor, particularly in early stage NSCLC. The combination of EGFR gene amplification and p-JAK1 expression may be a novel target for the selection of individual therapy strategies and predicting the effects of therapy for NSCLC.
Traumatic grief treatment: a pilot study.

OBJECTIVE The effects of a treatment program targeting debilitating grief symptoms were tested in a pilot study. METHOD Twenty-one individuals experiencing traumatic grief were recruited for participation, and 13 completed the full 4-month protocol. The treatment protocol used imaginal re-living of the death, in vivo exposure to avoided activities and situations, and interpersonal therapy. RESULTS Significant improvement in grief symptoms and associated anxiety and depression was observed for both completer and intent-to-treat groups. CONCLUSIONS The traumatic grief treatment protocol appears to be a promising intervention for debilitating grief.
Germline mutations in the multiple endocrine neoplasia type 1 gene: Evidence for frequent splicing defects

Multiple endocrine neoplasia type 1 (MEN 1) is a familial cancer syndrome characterized by parathyroid hyperplasia, pituitary adenomas, and neuroendocrine tumors of the pancreas and duodenum. In 1997, the MEN1 tumor suppressor gene was identified, and numerous germline mutations have been reported to be distributed throughout the gene. We used single strand conformational variant (SSCV) analysis to search for germline mutations in the members of 33 kindreds with a confirmed diagnosis of MEN 1. SSCV analysis revealed 25 conformational variants representing germline mutations that are predicted to result in loss of normal menin function. Twenty different disease‐associated mutations were identified: five resulting in potential abnormal RNA splicing, two missense mutations, seven nonsense mutations, and six frameshift mutations. The aberrant splice products were identified and confirmed by RT‐PCR and direct sequence analysis for two of the five splice mutations. Sixteen of the 20 (80%) mutations identified have not been previously reported. Mutations were not identified in eight kindreds with signs and symptoms consistent with MEN 1. The SSCV analysis revealed mutations in 76% (25 of 33) of the kindreds investigated, thus showing SSCV analysis to be a reliable mutation detection strategy. One‐fifth of the mutations identified in this study involve intron sequences, therefore, highlighting the importance of including intron sequences in the search for germline mutations in the MEN1 gene. The need to investigate the entire gene when characterizing new MEN 1 families presents challenges in the translation of genetic studies to efficient clinical diagnostic tests. Hum Mutat 13:175–185, 1999. © 1999 Wiley‐Liss, Inc.
Prevalence of dental developmental anomalies: a radiographic study.

OBJECTIVES To determine the prevalence of developmental dental anomalies in patients attending the Dental Faculty of Medical University of Yazd, Iran and the gender differences of these anomalies. DESIGN A retrospective study based on the panoramic radiographs of 480 patients. Patients referred for panoramic radiographs were clinically examined, a detailed family history of any dental anomalies in their first and second degree relatives was obtained and finally their radiographs were studied in detail for the presence of dental anomalies. RESULTS 40.8% of the patients had dental anomalies. The more common anomalies were dilaceration (15%), impacted teeth (8.3%) and taurodontism (7.5%) and supernumerary teeth (3.5%). Macrodontia and fusion were detected in a few radiographs (0.2%). 49.1% of male patients had dental anomalies compared to 33.8% of females. Dilaceration, taurodontism and supernumerary teeth were found to be more prevalent in men than women, whereas impacted teeth, microdontia and gemination were more frequent in women. Family history of dental anomalies was positive in 34% of the cases. Taurodontism, gemination, dens in dente and talon cusp were specifically limited to the patients under 20 year's old, while the prevalence of other anomalies was almost the same in all groups. CONCLUSION Dilaceration, impaction and taurodontism were relatively common in the studied populaton. A family history of dental anomalies was positive in a third of cases.
Revisiting the Sulfur‐Water Chemical System in the Middle Atmosphere of Venus

Sulfur‐water chemistry plays an important role in the middle atmosphere of Venus. Ground‐based observations have found that simultaneously observed SO2 and H2O at ~64 km vary with time and are temporally anticorrelated. To understand these observations, we explore the sulfur‐water chemical system using a one‐dimensional chemistry‐diffusion model. We find that SO2 and H2O mixing ratios above the clouds are highly dependent on mixing ratios of the two species at the middle cloud top (58 km). The behavior of sulfur‐water chemical system can be classified into three regimes, but there is no abrupt transition among these regimes. In particular, there is no bifurcation behavior as previously claimed. We also find that the SO2 self‐shielding effect causes H2O above the clouds to respond to the middle cloud top in a nonmonotonic fashion. Through comparison with observations, we find that mixing ratio variations at the middle cloud top can explain the observed variability of SO2 and H2O. The sulfur‐water chemistry in the middle atmosphere is responsible for the H2O‐SO2 anticorrelation at 64 km. Eddy transport change alone cannot explain the variations of both species. These results imply that variations of species abundance in the middle atmosphere are significantly influenced by the lower atmospheric processes. Continued ground‐based measurements of the coevolution of SO2 and H2O above the clouds and new spacecraft missions will be crucial for uncovering the complicated processes underlying the interaction among the lower atmosphere, the clouds, and the middle atmosphere of Venus.
Systematic Mapping of WNT-FZD Protein Interactions Reveals Functional Selectivity by Distinct WNT-FZD Pairs*

Background: WNT-FZD specificity and signaling outcome have not been systematically mapped so far. Results: WNTs show selective binding to FZDs, and respective WNT-FZD pairs exert functional selectivity in different downstream signaling pathways. Conclusion: The WNT-FZD signaling system provides ligand-receptor selectivity. Significance: Understanding WNT-FZD selectivity is crucial for development of WNT pathway inhibitors and further understanding of molecular interactions within the WNT receptor signaling complex. The seven-transmembrane-spanning receptors of the FZD1–10 class are bound and activated by the WNT family of lipoglycoproteins, thereby inducing a complex network of signaling pathways. However, the specificity of the interaction between mammalian WNT and FZD proteins and the subsequent signaling cascade downstream of the different WNT-FZD pairs have not been systematically addressed to date. In this study, we determined the binding affinities of various WNTs for different members of the FZD family by using bio-layer interferometry and characterized their functional selectivity in a cell system. Using purified WNTs, we show that different FZD cysteine-rich domains prefer to bind to distinct WNTs with fast on-rates and slow off-rates. In a 32D cell-based system engineered to overexpress FZD2, FZD4, or FZD5, we found that WNT-3A (but not WNT-4, -5A, or -9B) activated the WNT-β-catenin pathway through FZD2/4/5 as measured by phosphorylation of LRP6 and β-catenin stabilization. Surprisingly, different WNT-FZD pairs showed differential effects on phosphorylation of DVL2 and DVL3, revealing a previously unappreciated DVL isoform selectivity by different WNT-FZD pairs in 32D cells. In summary, we present extensive mapping of WNT-FZD cysteine-rich domain interactions complemented by analysis of WNT-FZD pair functionality in a unique cell system expressing individual FZD isoforms. Differential WNT-FZD binding and selective functional readouts suggest that endogenous WNT ligands evolved with an intrinsic natural bias toward different downstream signaling pathways, a phenomenon that could be of great importance in the design of FZD-targeting drugs.