Miracle-dz/UniFAR-FTUs huggingface dataset:
Predictors and Management of Loss of Response to Vedolizumab in Inflammatory Bowel Disease.

Background We quantified loss of response (LOR) to vedolizumab (VDZ) in clinical practice and assessed the effectiveness of VDZ dose intensification for managing LOR. Methods Retrospective review (May 2014-December 2016) of a prospectively maintained inflammatory bowel disease (IBD) registry. Kaplan-Meier estimates were used to determine rates of LOR to VDZ . Independent predictors of LOR were identified using univariate and multivariable Cox proportional hazard regression. Success of recapturing response (>50% reduction in symptoms from baseline) and remission (complete resolution of symptoms) after dose intensification was quantified. Results Cumulative rates for VDZ LOR were 20% at 6 months and 35% at 12 months, with slightly lower rates in Crohn's disease than in ulcerative colitis (6 months 15% vs 18% and 12 months 30% vs 39%, P = 0.03). On multivariable analysis, LOR to a tumor necrosis factor (TNF) antagonist before VDZ use was associated with an increased risk for LOR to VDZ [hazard ratio (HR) 1.93; 95% confidence interval (CI) 1.25-2.97] in all patients. For Crohn's disease patients specifically, higher baseline C-reactive protein concentration was associated with increased risk for LOR to VDZ (HR 1.01 per mg/dL increase, 95% CI 1.01-1.02). Shortening of VDZ infusion interval from 8 to every 4 or 6 weeks recaptured response in 49% and remission in 18% of patients. Conclusions LOR to a TNF antagonist before VDZ use and higher baseline C-reactive protein are important predictors of VDZ LOR. Treatment response can be recaptured in almost half of these patients with VDZ infusion interval shortening.
A Review of Hydrogen Sulfide Synthesis, Metabolism, and Measurement: Is Modulation of Hydrogen Sulfide a Novel Therapeutic for Cancer?

Significance: Hydrogen sulfide (H2S) has been recognized as the third gaseous transmitter alongside nitric oxide and carbon monoxide. In the past decade, numerous studies have demonstrated an active role of H2S in the context of cancer biology. Recent Advances: The three H2S-producing enzymes, namely cystathionine γ-lyase (CSE), cystathionine β-synthase (CBS), and 3-mercaptopyruvate sulfurtransferase (3MST), have been found to be highly expressed in numerous types of cancer. Moreover, inhibition of CBS has shown anti-tumor activity, particularly in colon cancer, ovarian cancer, and breast cancer, whereas the consequence of CSE or 3MST inhibition remains largely unexplored in cancer cells. Intriguingly, H2S donation at high amounts or a long time duration has also been observed to induce cancer cell apoptosis in vitro and in vivo while sparing noncancerous fibroblast cells. Therefore, a bell-shaped model has been proposed to explain the role of H2S in cancer development. Specifically, endogenous H2S or a relatively low level of exogenous H2S may exhibit a pro-cancer effect, whereas exposure to H2S at a higher amount or for a long period may lead to cancer cell death. This indicates that inhibition of H2S biosynthesis and H2S supplementation serve as two distinct ways for cancer treatment. This paradoxical role of H2S has stimulated the enthusiasm for the development of novel CBS inhibitors, H2S donors, and H2S-releasing hybrids. Critical Issues: A clear relationship between H2S level and cancer progression remains lacking. The possibility that the altered levels of these byproducts have influenced the cell viability of cancer cells has not been excluded in previous studies when modulating H2S producing enzymes. Future Directions: The consequence of CSE or 3MST inhibition in cancer cells need to be examined in the future. Better portrayal of the crosstalk among these gaseous transmitters may not only lead to an in-depth understanding of cancer progression but also shed light on novel strategies for cancer therapy.
COCO-CN for Cross-Lingual Image Tagging, Captioning, and Retrieval

This paper contributes to cross-lingual image annotation and retrieval in terms of data and baseline methods. We propose COCO-CN, a novel dataset enriching MS-COCO with manually written Chinese sentences and tags. For effective annotation acquisition, we develop a recommendation-assisted collective annotation system, automatically providing an annotator with several tags and sentences deemed to be relevant with respect to the pictorial content. Having 20 342 images annotated with 27 218 Chinese sentences and 70 993 tags, COCO-CN is currently the largest Chinese–English dataset that provides a unified and challenging platform for cross-lingual image tagging, captioning, and retrieval. We develop conceptually simple yet effective methods per task for learning from cross-lingual resources. Extensive experiments on the three tasks justify the viability of the proposed dataset and methods. Data and code are publicly available at https://github.com/li-xirong/coco-cn.
Lipid‐lowering medication is associated with decreased risk of diabetic retinopathy and the need for treatment in patients with type 2 diabetes: A real‐world observational analysis of a health claims database

Fenofibrate and statins reduced the need for diabetic retinopathy (DR)‐related treatment in clinical trials. We aimed to determine whether use of lipid‐lowering medication reduces the risk of DR and the need for treatment in patients with type 2 diabetes using a real‐world health claims database.
An AAST-MITC analysis of pancreatic trauma: Staple or sew? Resect or drain?

INTRODUCTION Pancreatic trauma results in high morbidity and mortality, in part caused by the delay in diagnosis and subsequent organ dysfunction. Optimal operative management strategies remain unclear. We therefore sought to determine CT accuracy in diagnosing pancreatic injury and the morbidity and mortality associated with varying operative strategies. METHODS We created a multicenter, pancreatic trauma registry from 18 Level 1 and 2 trauma centers. Adult, blunt or penetrating injured patients from 2005 to 2012 were analyzed. Sensitivity and specificity of CT scan identification of main pancreatic duct injury was calculated against operative findings. Independent predictors for mortality, adult respiratory distress syndrome (ARDS), and pancreatic fistula and/or pseudocyst were identified through multivariate regression analysis. The association between outcomes and operative management was measured. RESULTS We identified 704 pancreatic injury patients of whom 584 (83%) underwent a pancreas-related procedure. CT grade modestly correlated with OR grade (r2 0.39) missing 10 ductal injuries (9 grade III, 1 grade IV) providing 78.7% sensitivity and 61.6% specificity. Independent predictors of mortality were age, Injury Severity Score (ISS), lactate, and number of packed red blood cells transfused. Independent predictors of ARDS were ISS, Glasgow Coma Scale score, and pancreatic fistula (OR 5.2, 2.6–10.1). Among grade III injuries (n = 158, 22.4%), the risk of pancreatic fistula/pseudocyst was reduced when the end of the pancreas was stapled (OR 0.21, 95% CI 0.05–0.9) compared with sewn and was not affected by duct stitch placement. Drainage alone in grades IV (n = 25) and V (n = 24) injuries carried increased risk of pancreatic fistula/pseudocyst (OR 8.3, 95% CI 2.2–32.9). CONCLUSION CT is insufficiently sensitive to reliably identify pancreatic duct injury. Patients with grade III injuries should have their resection site stapled instead of sewn and a duct stitch is unnecessary. Further study is needed to determine if drainage alone should be employed in grades IV and V injuries. LEVEL OF EVIDENCE Epidemiologic/Diagnostic study, level III.
The expression of selected molecular markers of immune tolerance in psoriatic patients.

BACKGROUND Psoriasis is a chronic autoinflammatory disease whose underlying molecular mechanisms remain unclear. The disease is mediated by the cells and molecules of both the innate and adaptive immune systems. Some T cell surface molecules, including neuropilin-1 (NRP1), programmed death 1 (PD-1) and the human leukocyte antigen G (HLA-G), are known to play a role in the maintenance of immune tolerance. OBJECTIVES The aim of this study was to investigate HLA-G, NRP1 and programmed cell death gene (PDCD1) mRNA expression in psoriatic patients. MATERIAL AND METHODS The study included 72 psoriatic patients and 35 healthy individuals. Twentyone patients (29.17%) suffered from concomitant psoriatic arthritis. The mRNA expression of HLA-G, NRP1, and PDCD1 were determined using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). The severity of skin lesions was assessed by means of the Psoriasis Area and Severity Index (PASI), Body Surface Area (BSA), the Patient Global Assessment (PGA), and the Dermatology Life Quality Index (DLQI). RESULTS The median value of the PASI was 11.5, and of BSA was 15.8%. The expressions of NRP1 and PDCD1, but not HLA-G, were significantly lower in psoriatic patients in comparison with the control group. The expression of HLA-G, NRP1 and PDCD1 were not significantly different in the psoriatic arthritis and psoriasis vulgaris patients. CONCLUSIONS The results of this study suggest that the molecular markers of immune tolerance, i.e., HLA-G, NRP1, and PD-1, may be involved in the immune response in psoriatic patients.
Laurentide Ice Sheet basal temperatures at the Last Glacial Cycle as inferred from borehole data

Laurentide Ice Sheet basal temperatures at the Last Glacial Cycle as inferred from borehole data Carolyne Pickler1, Hugo Beltrami2,3, and Jean-Claude Mareschal1 1GEOTOP, Centre de Recherche en Géochimie et en Géodynamique, Université du Québec à Montréal, Canada 2Climate & Atmospheric Sciences Institute and Department of Earth Sciences, St. Francis Xavier University, Antigonish, Nova Scotia, Canada 3Centre ESCER pour l’étude et la simulation du climat à l’échelle régionale, Université du Québec à Montréal, Canada Correspondence to: Hugo Beltrami(hugo@stfx.ca)
Megakaryocyte apoptosis in immune thrombocytopenia

Abstract The mechanisms of platelet underproduction in immune thrombocytopenia (ITP) remain unknown. While the number of megakaryocytes is normal or increased in ITP bone marrow, further studies of megakaryocyte integrity are needed. Megakaryocytes are responsible for the production of platelets in the bone marrow, and they are possible targets of immune-mediated injury in ITP. Since the biological process of megakaryocyte apoptosis impacts platelet production, we investigated megakaryocyte DNA fragmentation as a marker of apoptosis from ITP bone marrow biopsies. Archived bone marrow biopsy specimens from ITP patients, bone marrow specimens from controls with normal platelet counts, and bone marrow specimens from thrombocytopenic controls with myelodysplastic syndrome (MDS) were evaluated. Sections were stained with anti-CD61 for megakaryocyte enumeration, and terminal deoxynucleotidyl transferase dUTP nick-end labeling was used as an apoptotic indicator. In ITP patients, megakaryocyte apoptosis was reduced compared to nonthrombocytopenic controls. Megakaryocyte apoptosis was similarly reduced in thrombocytopenic patients with MDS. These results suggest a link between megakaryocyte apoptosis and platelet production.
Thyroid Hormones Play Role in Sarcopenia and Myopathies

Skeletal muscle maintains posture and enables movement by converting chemical energy into mechanical energy, further contributing to basal energy metabolism. Thyroid hormones (thyroxine, or T4, and triiodothyronine, or T3) participate in contractile function, metabolic processes, myogenesis and regeneration of skeletal muscle. T3 classically modulates gene expression after binding to thyroid hormone nuclear receptors. Thyroid hormone effects depend on nuclear receptor occupancy, which is directly related to intracellular T3 levels. Sarcolemmal thyroid hormone levels are regulated by their transport across the plasma membrane by specific transporters, as well as by the action of deiodinases types 2 and 3, which can activate or inactivate T4 and T3. Thyroid hormone level oscillations have been associated with the worsening of many myopathies such as myasthenia gravis, Duchenne muscular dystrophy (DMD) and rhabdomyolysis. During aging skeletal muscle show a decrease in mass and quality, known as sarcopenia. There is increasing evidence that thyroid hormones could have a role in the sarcopenic process. Therefore, in this review, we aim to discuss the main effects of thyroid hormones in skeletal muscular aging processes and myopathy-related pathologies.
Facade Segmentation in the Wild

Urban facade segmentation from automatically acquired imagery, in contrast to traditional image segmentation, poses several unique challenges. 360-degree photospheres captured from vehicles are an effective way to capture a large number of images, but this data presents difficult-to-model warping and stitching artifacts. In addition, each pixel can belong to multiple facade elements, and different facade elements (e.g., window, balcony, sill, etc.) are correlated and vary wildly in their characteristics. In this paper, we propose three network architectures of varying complexity to achieve multilabel semantic segmentation of facade images while exploiting their unique characteristics. Specifically, we propose a MULTIFACSEGNET architecture to assign multiple labels to each pixel, a SEPARABLE architecture as a low-rank formulation that encourages extraction of rectangular elements, and a COMPATIBILITY network that simultaneously seeks segmentation across facade element types allowing the network to 'see' intermediate output probabilities of the various facade element classes. Our results on benchmark datasets show significant improvements over existing facade segmentation approaches for the typical facade elements. For example, on one commonly used dataset, the accuracy scores for window(the most important architectural element) increases from 0.91 to 0.97 percent compared to the best competing method, and comparable improvements on other element types.
Genetic variants in autism-related CNTNAP2 impair axonal growth of cortical neurons

The CNTNAP2 gene, coding for the cell adhesion glycoprotein Caspr2, is thought to be one of the major susceptibility genes for autism spectrum disorder (ASD). A large number of rare heterozygous missense CNTNAP2 variants have been identified in ASD patients. However, most of them are inherited from an unaffected parent, questioning their clinical significance. In the present study, we evaluate their impact on neurodevelopmental functions of Caspr2 in a heterozygous genetic background. Performing cortical neuron cultures from mouse embryos, we demonstrate that Caspr2 plays a dose-dependent role in axon growth in vitro. Loss of one Cntnap2 allele is sufficient to elicit axonal growth alteration, revealing a situation that may be relevant for CNTNAP2 heterozygosity in ASD patients. Then, we show that the two ASD variants I869T and G731S, which present impaired binding to Contactin2/TAG-1, do not rescue axonal growth deficits. We find that the variant R1119H leading to protein trafficking defects and retention in the endoplasmic reticulum has a dominant-negative effect on heterozygous Cntnap2 cortical neuron axon growth, through oligomerization with wild-type Caspr2. Finally, we identify an additional variant (N407S) with a dominant-negative effect on axon growth although it is well-localized at the membrane and properly binds to Contactin2. Thus, our data identify a new neurodevelopmental function for Caspr2, the dysregulation of which may contribute to clinical manifestations of ASD, and provide evidence that CNTNAP2 heterozygous missense variants may contribute to pathogenicity in ASD, through selective mechanisms.
Hemisensory disturbances in patients with complex regional pain syndrome

Abstract Sensory disturbances often spread beyond the site of injury in complex regional pain syndrome (CRPS) but whether this applies equally to CRPS I and II, or changes across the course of the disease, is unknown. Establishing this is important, because different symptom profiles in CRPS I and II, or in acute vs chronic CRPS, might infer different pathophysiology and treatment approaches. To explore these questions, sensory disturbances were assessed in the limbs and forehead of 71 patients with CRPS I and 33 patients with CRPS II. Pain had persisted up to 12 months in 32 patients, for 13 to 36 months in 29 patients, and for longer than this in 43 patients. Patients with CRPS I were more likely to be female, and pain was more likely to be present in an additional limb, than patients with CRPS II. Conversely, pain was more likely to be associated with sensory deficits and allodynia in patients with CRPS II than CRPS I. Nevertheless, heightened sensitivity, allodynia, and/or hyperalgesia to mechanical and thermal stimuli were detected in a hemisensory distribution ipsilateral to the affected limb in both forms of CRPS. Some of these hemisensory disturbances strengthened with chronicity of pain. These findings suggest that heightened excitability of nociceptive pathways in CRPS spreads to hemisensory convergence points in the brainstem or higher brain centres, possibly in association with compromised pain controls. The similarity of symptom profiles in chronic CRPS I and II implies shared mechanisms despite different triggers.
Functional changes of the SCN in spontaneous hypertension but not after the induction of hypertension

ABSTRACT The present study investigates the circadian behavior of spontaneously hypertensive rats (SHRs) during the pre-hypertensive and hypertensive stage, with the aim to gain insight into whether observed changes in the functionality of suprachiasmatic nucleus (SCN) in the hypertensive state are cause or consequence of hypertension. Four types of animals were used in this study: (1) SHRs which develop hypertension genetically; (2) their normotensive controls, Wistar Kyoto rats (WKYs); (3) Wistar rats whereby hypertension was surgically induced (2 Kidney 1 Clamp (2K1C) method); and (4) sham-operated control Wistar rats. Period length and activity levels and amplitude changes of locomotor and wheel running activity were determined, in constant conditions, as a measure of the functionality of the SCN. Hereto two conditions were used, constant darkness (0 lux) and constant dim (5 lux) light. SHRs showed a shortened period of their locomotor and running wheel activity rhythms in constant darkness during both pre-hypertensive and hypertensive stages and exhibited period lengthening in constant dim light conditions, only during hypertensive stages. Total amount as well as the amplitude of daily running wheel rhythms showed an inverse correlation with the period length, and this relation was significantly different in SHRs compared to WKYs. None of the aforementioned changes in circadian rhythms were observed after the surgical induction of hypertension. The present findings suggest early functional changes of the SCN in the etiology of spontaneous hypertension.
A Simple Cache Model for Image Recognition

Training large-scale image recognition models is computationally expensive. This raises the question of whether there might be simple ways to improve the test performance of an already trained model without having to re-train or fine-tune it with new data. Here, we show that, surprisingly, this is indeed possible. The key observation we make is that the layers of a deep network close to the output layer contain independent, easily extractable class-relevant information that is not contained in the output layer itself. We propose to extract this extra class-relevant information using a simple key-value cache memory to improve the classification performance of the model at test time. Our cache memory is directly inspired by a similar cache model previously proposed for language modeling (Grave et al., 2017). This cache component does not require any training or fine-tuning; it can be applied to any pre-trained model and, by properly setting only two hyper-parameters, leads to significant improvements in its classification performance. Improvements are observed across several architectures and datasets. In the cache component, using features extracted from layers close to the output (but not from the output layer itself) as keys leads to the largest improvements. Concatenating features from multiple layers to form keys can further improve performance over using single-layer features as keys. The cache component also has a regularizing effect, a simple consequence of which is that it substantially increases the robustness of models against adversarial attacks.
Current Role of Urethrolysis and Partial Excision in Patients Seeking Revision of Anti-Incontinence Sling

The study describes a contemporary population of patients undergoing sling excision and urethrolysis and explores the outcomes of these distinct procedures. Objectives Stress urinary incontinence is highly prevalent and sling surgery has increased since 2000. Urethrolysis traditionally had been standard management of complications after anti-incontinence surgery; however, partial excision is a less aggressive option. This study describes the different populations in a contemporary cohort that undergo sling excision and urethrolysis and their surgical outcomes. Methods Chart analysis was performed on patients assigned Current Procedural Terminology codes for removal or revision of sling for stress incontinence, urethrolysis, or revision of graft at our institution from 2010 to 2015. Demographics, indications, outcomes, and subsequent treatment were evaluated. Results A total of 110 patients underwent surgery and were included. Partial excision was performed on 82 patients and urethrolysis on 28 patients. About 32.7% had prior revision, and median length to revision was 3.1 years. Overall success was 75.0% for urethrolysis and 86.6% for partial excision. Without concomitant sling placement, stress incontinence developed in 25.0% of urethrolysis and 21.6% of partial excision patients. New onset overactive bladder symptoms developed in 21.4% of urethrolysis patients and 7.3% of partial excision, which was significantly different (P = 0.039). Conclusions Both approaches had good success, 75.0% for formal urethrolysis and 86.6% for partial excision. New onset urgency was lower for partial excision, but rates of all other complications were similar. These procedures are often used for different patient populations, and thus, outcomes are not meant to be directly compared. Future work on sling revision should report these procedures separately.
Injection Strategy for the Optimization of Therapeutic Temperature Profile Considering Irregular Tumors in Magnetic Hyperthermia

Magnetic hyperthermia uses the therapeutic heat from magnetic nanoparticles (MNPs) under an external alternating magnetic field to ablate tumor cells. The temperature profile achieved during therapy is determined by the spatial distribution of MNPs within the tumor, which is a function of the injection velocity, dose, and concentration. The effects of injection strategy on the power dissipation of MNPs can then be described by using Gaussian’s distribution, in which two related parameters are introduced. This paper proposes a nonlinear optimization problem, which can be efficiently solved using simulated annealing algorithm, to optimize these two parameters for a proposed irregular tumor with two injection sites. Simulation results demonstrate that the effective area of treatment temperature distribution can be significantly increased with respect to traditional methods from the literature when a set of bad initial values is considered. In addition, for good initial values, the results obtained by the proposed method are better than the ones obtained by traditional methods.