Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparative parallel assessment of a transfer device in reducing 5-fluorouracil environmental contamination inside positive air pressure isolators

The environmental contamination of the antineoplastic drugs circuit, due to the centralization of preparation and the increased number of the patients treated, brought about a new occupational hazard: the chronic exposure to low doses of antineoplastic drugs. The rationalization of the hospital budgets imposes a meticulous assessment of the devices available for the preparation, in order to justify their interest, even their cost. A prospective comparative study with parallel arms was led inside the Pharmacy of the Institut de Cancerologie de la Loire in order to evaluate the Spike Swan®, a transfer device. The aim was to assess the Spike Swan® effectiveness. The antineoplastic drugs environmental contamination within the isolators is considered as a potential starting point for a larger dissemination of cytotoxic products. Therefore, the primary endpoint was the surface contamination level with 5-fluorouracil and the comparator was the standard preparation technique using needles and aeration needles. This study did not show significant effectiveness for the Spike Swan ® in reducing surface contamination. Nevertheless, this device could be used to prepare large volumes and to secure occasional handlers, because it is easy to handle.
Potent and broad HIV-neutralizing antibodies in memory B cells and plasma

Plasma is a source of broadly neutralizing antibodies for recombinant antibodies with enhanced potency and breadth. Engineering HIV immunity For rapidly mutating viruses such as HIV, antibodies that can neutralize more than one strain may have real potential as a therapeutic. Now, Williams et al. examine the ontogeny of broadly neutralizing antibodies (bnAbs) to the distal portion of the membrane-proximal external region (MPER) of HIV-1 gp41. They found similar clonal lineages of an MPER bnAb from both memory B cells and plasma, highlighting the viability of plasma as a source of bnAbs. These lineages shared an autoreactive unmutated common ancestor, suggesting that tolerance must be overcome for bnAb induction. The authors then engineered chimeric antibodies from the plasma and memory B cells that neutralized most HIV-1 strains. Induction of broadly neutralizing antibodies (bnAbs) is a goal of HIV-1 vaccine development. Antibody 10E8, reactive with the distal portion of the membrane-proximal external region (MPER) of HIV-1 gp41, is broadly neutralizing. However, the ontogeny of distal MPER antibodies and the relationship of memory B cell to plasma bnAbs are poorly understood. HIV-1–specific memory B cell flow sorting and proteomic identification of anti-MPER plasma antibodies from an HIV-1–infected individual were used to isolate broadly neutralizing distal MPER bnAbs of the same B cell clonal lineage. Structural analysis demonstrated that antibodies from memory B cells and plasma recognized the envelope gp41 bnAb epitope in a distinct orientation compared with other distal MPER bnAbs. The unmutated common ancestor of this distal MPER bnAb was autoreactive, suggesting lineage immune tolerance control. Construction of chimeric antibodies of memory B cell and plasma antibodies yielded a bnAb that potently neutralized most HIV-1 strains.
Fatmax in children and adolescents: A review

Abstract The purpose of this review is to summarize and critically examine the literature that has determined Fatmax in children and adolescents (young people). Maximizing fat oxidation during exercise may be beneficial for health, particularly in the management of metabolic diseases such as obesity and type 2 diabetes. Exercise intensity largely determines fat oxidation during exercise. Fatmax is the relative exercise intensity that elicits the highest fat oxidation rate and has received increasing attention in recent years. Studies in young people have demonstrated that there is considerable inter-individual variation in Fatmax, which generally occurs between 30 and 60% of peak oxygen uptake. Factors that may influence Fatmax in young people include body composition, physical maturation, and exercise training. Several researchers have suggested that Fatmax and fat oxidation rates may be reduced in obese compared with non-obese young people. Fatmax and fat oxidation rates may also decrease with maturational status. Much of the research on Fatmax in young people has focused on boys, with research comparing Fatmax between the sexes extremely limited. The available evidence indicates that Fatmax is similar between boys and girls, whereas absolute rates of fat oxidation may be higher in boys. The use of Fatmax as a training tool for the obese has been examined in young people and may have implications for improving fat oxidation and various health markers. However, several weaknesses may be highlighted in many studies that have identified Fatmax in young people, and inconsistencies in the methods used to determine Fatmax limit comparisons between studies. Therefore, conclusions based on these findings require further investigation. Additional research is also required to assess the influence of other factors associated with Fatmax in young people, including exercise mode, cardiorespiratory fitness, and free-living physical activity.
Neutrophil cytoplasts induce TH17 differentiation and skew inflammation toward neutrophilia in severe asthma

Neutrophil cytoplasts promote TH17 inflammation. Nefarious neutrophil cytoplasts In addition to DNA release, neutrophil extracellular trap (NET) formation can result in enucleated cells called cytoplasts. Krishnamoorthy et al. examined how neutrophil cytoplasts contribute to asthmatic inflammation in mouse models of allergic lung inflammation and in asthmatic patients. Airway exposure of mice to LPS with house dust mite allergen induced NET formation in the lung that was associated with IL-17 production upon subsequent exposure to allergen. Cytoplasts and not neutrophil DNA released in NETosis triggered neutrophilia upon allergen exposure, and cytoplasts alone were sufficient to induce IL-17 production by antigen-specific T cells. Cytoplasts also correlated with IL-17 levels in bronchoalveolar lavage fluid from severe asthmatics. These findings provide insight into how neutrophil cytoplasts can contribute to asthma severity. Severe asthma is a debilitating and treatment refractory disease. As many as half of these patients have complex neutrophil-predominant lung inflammation that is distinct from milder asthma with type 2 eosinophilic inflammation. New insights into severe asthma pathogenesis are needed. Concomitant exposure of mice to an aeroallergen and endotoxin during sensitization resulted in complex neutrophilic immune responses to allergen alone during later airway challenge. Unlike allergen alone, sensitization with allergen and endotoxin led to NETosis. In addition to neutrophil extracellular traps (NETs), enucleated neutrophil cytoplasts were evident in the lungs. Surprisingly, allergen-driven airway neutrophilia was decreased in peptidyl arginine deiminase 4–deficient mice with defective NETosis but not by deoxyribonuclease treatment, implicating the cytoplasts for the non–type 2 immune responses to allergen. Neutrophil cytoplasts were also present in mediastinal lymph nodes, and the cytoplasts activated lung dendritic cells in vitro to trigger antigen-specific interleukin-17 (IL-17) production from naïve CD4+ T cells. Bronchoalveolar lavage fluid from patients with severe asthma and high neutrophil counts had detectable NETs and cytoplasts that were positively correlated with IL-17 levels. Together, these translational findings have identified neutrophil cytoplast formation in asthmatic lung inflammation and linked the cytoplasts to T helper 17–mediated neutrophilic inflammation in severe asthma.
Pulmonary Complications of Sickle Cell Disease

Sickle cell anemia and its variants are inher ited disorders of hemoglobin (Hb) structure char acterized by hemolytic anemia, frequent infections, and microvascular obstruction by rigid erythro cytes (RBC) producing acute and chronic ischemia and ultimately resulting in organ damage from in farction, necrosis, and fibrosis. 1 The clinical fea tures of the disease are the direct result of the substitution of valine for glutamic acid at position 6 of the beta-globin subunit of the hemoglobin tetramer, which allows intracellular polymerization of Hb molecules following deoxygenation and me diates the morphologic transformation from the normally flexible, biconcave shape to the rigid sickle shape. Repetitive episodes of sickling cause RBC dehydration, cytoplasmic and membrane rigidity, and an increase in intracellular Hb con centration. These alterations produce a heteroge neous population of RBC of increasing density, including very dense discocytes and irreversibly sickled cells (ISC). 1-3 These very dense discocytes and ISC are poorly deformable and are responsi ble for the elevated blood viscosity and microvas cular occlusion of the disease. 2,4 Sickle cell anemia is the term applied to the homozygous form of the disease (Hb SS); it is the most common variant and generally has the most severe clinical manifestations. 5 Other variants are due to the simultaneous inheritance of compound heterozygous states for Hb S and another hemo globin that interacts with Hb S to participate in polymer formation, thus causing disease. Hemo globinopathy SC results from the inheritance of the beta-S gene and the beta-C gene in-trans. Hb SC tends to have a later onset of symptoms, very mild anemia, and splenomegaly rather than autosple-nectomy.
Efficient Approach for RLS Type Learning in TSK Neural Fuzzy Systems

This paper presents an efficient approach for the use of recursive least square (RLS) learning algorithm in Takagi–Sugeno–Kang neural fuzzy systems. In the use of RLS, reduced covariance matrix, of which the off-diagonal blocks defining the correlation between rules are set to zeros, may be employed to reduce computational burden. However, as reported in the literature, the performance of such an approach is slightly worse than that of using the full covariance matrix. In this paper, we proposed a so-called enhanced local learning concept in which a threshold is considered to stop learning for those less fired rules. It can be found from our experiments that the proposed approach can have better performances than that of using the full covariance matrix. Enhanced local learning method can be more active on the structure learning phase. Thus, the method not only can stop the update for insufficiently fired rules to reduce disturbances in self-constructing neural fuzzy inference network but also raises the learning speed on structure learning phase by using a large backpropagation learning constant.
Syndrome of Inappropriate Antidiuretic Hormone after vinorelbine treatment

Background Among oncologic patients, Syndrome of Inappropriate Antidiuretic Hormone is a common cause of hyponatremia, a prevalent electrolyte disorder. There are many causes for Syndrome of Inappropriate Antidiuretic Hormone, including chemotherapy medications. To date, only three cases associating vinorelbine and Syndrome of Inappropriate Antidiuretic Hormone have been published. Case A 47-year-old woman with stage IIIC serous ovarian adenocarcinoma developed life-threatening hyponatremia (124 mmol/L) after three cycles of vinorelbine. Assessment revealed Syndrome of Inappropriate Antidiuretic Hormone as the most likely culprit. Conservative managements including free fluid restriction normalized her sodium level and Syndrome of Inappropriate Antidiuretic Hormone resolved after vinorelbine discontinuation. Conclusion Vinorelbine can cause Syndrome of Inappropriate Antidiuretic Hormone. It is important to monitor sodium concentration during vinorelbine treatment to avoid serious neurological complications of hyponatremia and to improve patient's quality of life.
Hypersensitivity reactions to etoposide phosphate

Etoposide phosphate is a prodrug of intravenous etoposide recommended for use in patients with demonstrated allergy to etoposide. We have previously published a case series comprising six patients who were successfully treated with etoposide phosphate following preceding etoposide hypersensitivity. In this new paper we now present the cases of two patients who had allergic reactions to both etoposide and etoposide phosphate. As such, we suggest that whilst most patients with etoposide hypersensitivity can safely be treated with etoposide phosphate, a small number are at risk of an additional allergic reaction to etoposide phosphate. Patients being treated for the first time with etoposide phosphate after etoposide allergy should receive their first dose under medical supervision.
Intracerebral hogkin’s lymphoma in a patient with human immunodeficiency virus

Central nervous system (CNS) involvement by Hodgkin Lymphoma (HL) is rarely reported. Retrospective and prospective cohort studies suggest an incidence of 0.2–0.5%, mostly in relapsed disease. In spite of a 3 to 18-fold increased risk of HL in patients with human immunodeficiency virus (HIV), only two cases have been reported so far. In this paper, we now report a third case of HIV patient with HL who progressed with isolated CNS infiltration after a standard chemotherapy induced clinical remission. In 1991, when the first case of intracerebral involvement in HIV+ HL was reported an increase of this type of cases would have been expected, but only one more case has been reported since then.
Kinome siRNA Screen Identifies Regulators of Ciliogenesis and Hedgehog Signal Transduction

Cdc2l1is a component of the Hh signaling pathway and opposes the activity of the negative regulator Sufu. Modulating Hedgehog Signals Signaling initiated by Hedgehog (Hh) ligands is critical to tissue patterning in both vertebrates and invertebrates; however, the specific downstream mechanisms are distinct. For instance, Fused, a kinase crucial to fly Hh signaling, does not appear to be essential to Hh signaling in mammals. Evangelista et al. screened a mouse kinome small interfering RNA library and used stringent criteria to validate candidates for genes encoding proteins that enhance Hh signaling. Two of these, Nek1 and Prkra, appeared to regulate Hh signaling indirectly by affecting primary cilia formation. The kinase Cdc2l1, however, interacted with the negative regulator of Hh signaling Suppressor of Fused, thereby relieving its inhibition of the Glioma-associated family of transcription factors, suggesting that Cdc2l1 plays a direct role in the Hh signal transduction cascade in vertebrates. Disruption or improper activation of the Hedgehog (Hh) pathway is associated with developmental abnormalities and cancer. Although characterized in Drosophila, the mechanisms that mediate the Hh signal downstream of the Smoothened (Smo) seven-transmembrane protein in vertebrates remain poorly understood. In particular, the Fused (Fu) kinase, which mediates Hh signaling in flies, is dispensable in mammals. To identify kinases that positively regulate the Hh pathway in mammals, we screened a mouse kinome small interfering RNA library and validated nine candidates that modulate Hh signaling. Among these candidates, Nek1 and Prkra did not directly function in the Hh pathway but exerted their effects on Hh signaling indirectly through a primary role in ciliogenesis. In contrast, another kinase, Cdc2l1, directly participated in the Hh pathway. Cdc2l1 was necessary and sufficient for activation of the Hh pathway, functioning downstream of Smo and upstream of the Glioma-associated (Gli) transcription factors. More specifically, Cdc2l1 interacted with the negative regulator Suppressor of Fused (Sufu) and relieved its inhibition on Gli, thus providing a mechanism for how Cdc2l1 might play a role in Hh signaling. Finally, with zebrafish as model organism, we showed that Cdc2l1 activated the Hh pathway in vivo. We propose that Cdc2l1 is a previously unrecognized member of the Hh signal transduction cascade.
Quantitative Phosphoproteomic Analysis of T Cell Receptor Signaling Reveals System-Wide Modulation of Protein-Protein Interactions

Serine-threonine phosphorylation plays a role in regulating the interactions among proteins involved in T cell responses. Further Interactions The binding of antigen to the T cell receptor (TCR) complex triggers a cascade of responses that culminate in T cell activation. Key to the initial stages of this cascade is the phosphorylation of tyrosine residues in proteins proximal to the TCR, which enables the recruitment of other proteins that contain phosphotyrosine-binding domains. Given its importance to TCR signaling, tyrosine phosphorylation of target proteins has received considerable attention. To view protein phosphorylation from a larger perspective, Mayya et al. performed a system-level phosphoproteomics analysis of the events triggered by TCR activation in the human Jurkat T cell line. They found that the status of hundreds of phosphorylation sites was modulated in response to stimulation of the TCR. In addition to identifying previously unknown TCR-responsive phosphorylation events, this analysis also suggests a role for phosphorylated serine and threonine residues in modulating protein-protein interactions between many proteins involved in T cell responses. Protein phosphorylation events during T cell receptor (TCR) signaling control the formation of complexes among proteins proximal to the TCR, the activation of kinase cascades, and the activation of transcription factors; however, the mode and extent of the influence of phosphorylation in coordinating the diverse phenomena associated with T cell activation are unclear. Therefore, we used the human Jurkat T cell leukemia cell line as a model system and performed large-scale quantitative phosphoproteomic analyses of TCR signaling. We identified 10,665 unique phosphorylation sites, of which 696 showed TCR-responsive changes. In addition, we analyzed broad trends in phosphorylation data sets to uncover underlying mechanisms associated with T cell activation. We found that, upon stimulation of the TCR, phosphorylation events extensively targeted protein modules involved in all of the salient phenomena associated with T cell activation: patterning of surface proteins, endocytosis of the TCR, formation of the F-actin cup, inside-out activation of integrins, polarization of microtubules, production of cytokines, and alternative splicing of messenger RNA. Further, case-by-case analysis of TCR-responsive phosphorylation sites on proteins belonging to relevant functional modules together with network analysis allowed us to deduce that serine-threonine (S-T) phosphorylation modulated protein-protein interactions (PPIs) in a system-wide fashion. We also provide experimental support for this inference by showing that phosphorylation of tubulin on six distinct serine residues abrogated PPIs during the assembly of microtubules. We propose that modulation of PPIs by stimulus-dependent changes in S-T phosphorylation state is a widespread phenomenon applicable to many other signaling systems.
Differential Requirement of mTOR in Postmitotic Tissues and Tumorigenesis

Conditional inactivation of mTor has little effect in adult mouse prostate, but suppresses tumor initiation and progression. Blocking mTor Signals The mammalian target of rapamycin (mTOR), a protein kinase critical to cell growth and proliferation, functions as part of two distinct multiprotein complexes. mTOR signaling is frequently disrupted in cancer; however pharmacological suppression of mTOR complex 1 (mTORC1) signaling has been of limited therapeutic efficacy. Nardella et al. show that, whereas conditional inactivation of mTOR activity (abrogating signaling through both complexes) has little effect in the adult mouse prostate, it markedly suppresses prostate cancer associated with loss of the tumor suppressor PTEN. Thus, mTOR inhibitors that target its catalytic activity may be more effective in cancer therapy than those that specifically inhibit signaling mediated through mTORC1. The mammalian target of rapamycin (mTOR) is a crucial effector in a complex signaling network commonly disrupted in cancer. mTOR exerts its multiple functions in the context of two different multiprotein complexes: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). Loss of the tumor suppressor PTEN (phosphatase and tensin homolog deleted from chromosome 10) can hyperactivate mTOR through AKT and represents one of the most frequent events in human prostate cancer. We show here that conditional inactivation of mTor in the adult mouse prostate is seemingly inconsequential for this postmitotic tissue. Conversely, inactivation of mTor leads to a marked suppression of Pten loss–induced tumor initiation and progression in the prostate. This suppression is more pronounced than that elicited by the sole pharmacological abrogation of mTORC1. Acute inactivation of mTor in vitro also highlights the differential requirement of mTor function in proliferating and transformed cells. Collectively, our data constitute a strong rationale for developing specific mTOR inhibitors targeting both mTORC1 and mTORC2 for the treatment of tumors triggered by PTEN deficiency and aberrant mTOR signaling.
Adaptive Critic Nonlinear Robust Control: A Survey

Adaptive dynamic programming (ADP) and reinforcement learning are quite relevant to each other when performing intelligent optimization. They are both regarded as promising methods involving important components of evaluation and improvement, at the background of information technology, such as artificial intelligence, big data, and deep learning. Although great progresses have been achieved and surveyed when addressing nonlinear optimal control problems, the research on robustness of ADP-based control strategies under uncertain environment has not been fully summarized. Hence, this survey reviews the recent main results of adaptive-critic-based robust control design of continuous-time nonlinear systems. The ADP-based nonlinear optimal regulation is reviewed, followed by robust stabilization of nonlinear systems with matched uncertainties, guaranteed cost control design of unmatched plants, and decentralized stabilization of interconnected systems. Additionally, further comprehensive discussions are presented, including event-based robust control design, improvement of the critic learning rule, nonlinear $ {H_{\infty }}$ control design, and several notes on future perspectives. By applying the ADP-based optimal and robust control methods to a practical power system and an overhead crane plant, two typical examples are provided to verify the effectiveness of theoretical results. Overall, this survey is beneficial to promote the development of adaptive critic control methods with robustness guarantee and the construction of higher level intelligent systems.
Age estimation from IV rib by phase analysis in Indian females

Metamorphosis at the sternal extremity of the rib has already been established as a reliable indicator of age at death by Iscan's phase method introduced in 1985. The purpose of this paper is to apply rib phase standards to an Indian sample to test if the progression of morphological changes follows the same age sequence. The rib sample shows that an accurate estimation of age can be made by direct examination of the bone itself. The sample consisted of 63 ribs of known age, sex, and race. The ribs were assigned to one of nine phases (0 through 8) based on changes noted at the costochondral junction. These included the formation of a pit, its depth and shape, configuration of the walls and rim surrounding it, and the overall texture and quality of the bone. Statistical analysis revealed that the features chosen to delineate the phases are valid predictors of age. This study has shown that the sternal rib can provide an accurate estimation of age in females spanning a mean age of 14 to 85 years.