Miracle-dz/UniFAR-FTUs huggingface dataset:
Aspectos ecológicos da tripanossomíase americana: XVI - dispersão e ciclos anuais de colônias de Triatoma sordida e de Panstrongylus megistus espontaneamente desenvolvidas em ecótopos artificiais

Sao apresentados novos dados sobre os ciclos anuais de colonias de Triatoma sordida desenvolvidas espontaneamente em galinheiros experimentais. Os resultados das observacoes confirmaram os relatados em trabalho anterior relativos ao relacionamento com o tempo e a sobrevivencia. Quanto a duracao dos estadios ninfais obteve-se valor superior, provavelmente devido ao maior numero de observacoes realizadas neste trabalho em comparacao com as precedentes. Computando-se os resultados destas observacoes com os das anteriormente feitas, tanto para T. sordida como para Panstrongylus megistus, foi possivel identificar com maior seguranca as epocas de dispersao ativa, no periodo anual por parte das formas adultas. Para o primeiro desses triaiomineos, o fenomeno atinge maior intensidade a partir de marco podendo prolongar-se ate maio. Para a outra especie, a dispersao ocorre principalmente a partir de outubro prolongando-se ate novembro. Tais aspectos permitem determinar as ocasioes mais propicias para a aplicacao das medidas de vigilância, como sendo aquelas em que a composicao das populacoes triatominicas e predominantemente constituida de primeiras ninfas e adultos. Assim sendo, tais epocas correspondem aos meses de julho e agosto para o T. sordida e de novembro e dezembro para o P. megistus, pelo menos nesta regiao sudeste do Brasil.
Abl tyrosine kinases in T‐cell signaling

Summary: Stimulation of the T‐cell antigen receptor (TCR) leads to the activation of signaling pathways that are essential for T‐cell development and the response of mature T cells to antigens. The TCR has no intrinsic catalytic activity, but TCR engagement results in tyrosine phosphorylation of downstream targets by non‐receptor tyrosine kinases. Three families of tyrosine kinases have long been recognized to play critical roles in TCR‐dependent signaling. They are the Src, ζ‐associated protein of 70 kDa, and Tec families of kinases. More recently, the Abelson (Abl) tyrosine kinases have been shown to be activated by TCR engagement and to be required for maximal TCR signaling. Using T‐cell conditional knockout mice deficient for Abl family kinases, Abl (Abl1) and Abl‐related gene (Arg) (Abl2), it was recently shown that loss of Abl kinases results in defective T‐cell development and a partial block in the transition to the CD4+CD8+ stage. Abl/Arg double null T cells exhibit impaired TCR‐induced signaling, proliferation, and cytokine production. Moreover, conditional knockout mice lacking Abl and Arg in T cells exhibit impaired CD8+ T‐cell expansion in vivo upon Listeria monocytogenes infection. Thus, Abl kinase signaling is required for both T‐cell development and mature T‐cell function.
Etapas del cambio, beneficios y barreras en actividad física y consumo de frutas y verduras en estudiantes universitarios de Santiago de Chile

Como linea base para disenar intervenciones de promocion y educacion, se determinaron las etapas del cambio, beneficios y barreras relacionados con la actividad fisica y el consumo de frutas y verduras en 449 estudiantes universitarios de ambos generos de Santiago. Se utilizaron instrumentos validados internacionalmente y adaptados en el pais. En actividad fisica, los hombres resultaron significativamente mas activos que las mujeres. Los beneficios mas destacados por ellos fueron "me hace sentir bien" o "me entretiene", en tanto el primero y "perder peso" fueron mas frecuentes en las mujeres. En ambos generos, la principal barrera fue la falta de tiempo. El 58% comia 1 a 2 porciones de frutas y verduras al dia y solo el 5% alcanzaba las 5 porciones. El principal beneficio de comer frutas y verduras se asocio a "estar sano/a", y las principales barreras fueron "me da flojera prepararlas" o "se me olvida comerlas", en ambos generos. Estos resultados se utilizaran en el diseno de intervenciones en promocion y educacion para estudiantes universitarios
Clinical applications of submucosal endoscopy

Purpose of reviewSubmucosal endoscopy with mucosal flap (SEMF), a new diagnostic and therapeutic intervention of flexible endoscopy, has been examined from the perspective of developmental laboratory work, procedural details, and results of early clinical experiences. Recent findingsDiagnostic natural orifice translumenal endoscopic surgery (NOTES) procedures, endolumenal achalasia myotomy, and submucosal tumor excision have been clinically performed with a SEMF method. The outcomes of these procedures were equivalent to standard surgery but with reduced morbidity. Some were accomplished under conscious sedation within the endoscopy unit. SummaryThe SEMF procedure was originally developed to provide safe access to the peritoneal cavity for NOTES procedures. In the SEMF method, the submucosal layer is endoscopically tunneled and the resultant space is used as an endoscopic path into deeper layers of the gut wall and an offset exit to the peritoneal cavity. Key to the method is the overlying mucosa which serves as a sealant flap minimizing the risk of soiling a body cavity with lumenal contents and the ease by which the entry point into the submucosal working space can be closed. Positive outcomes of the early SEMF clinical experiences validate that the submucosa can be transformed into a promising novel working space for flexible endoscopy.
Update review of the safety of sodium-glucose cotransporter 2 inhibitors for the treatment of patients with type 2 diabetes mellitus

ABSTRACT Introduction: The safety profile of sodium-glucose cotransporter 2 (SGLT2) inhibitors has continued to evolve with the availability of data from clinical trial programs, post-marketing pharmacovigilance and dedicated cardiovascular outcome trials. Areas covered: This article reviews the safety issues associated with the SGLT2 inhibitors canagliflozin, dapagliflozin, and empagliflozin, particularly the newer/emergent safety data related to US Food and Drug Administration statements regarding these three agents. Expert opinion: The safety profile of SGLT2 inhibitors is well defined, and the adverse event profile is largely consistent with their mechanism of action. These well-recognized events include genital mycotic infections and volume-associated adverse events. Serious safety issues detected more recently with SGLT2 inhibitor therapy, such as bone fractures, pyelonephritis, urosepsis, and ketoacidosis, have been uncommon. A robust improvement in cardiovascular outcomes in patients with type 2 diabetes mellitus (T2DM) was recently demonstrated with empagliflozin. Given the glucose-lowering efficacy, low risk of hypoglycemia, and other benefits associated with SGLT2 inhibitor therapy, this class of oral glucose-lowering medication is a valuable addition to treatment options for T2DM, and may play an increasingly prominent therapeutic role as emerging data are revealed.
The safety of sacubitril-valsartan for the treatment of chronic heart failure

ABSTRACT Introduction: Sacubitril-valsartan is a combination drug that contains the neprilysin inhibitor sacubitril and angiotensin II receptor blocker valsartan. In 2015, the US Food and Drug Administration approved sacubitril-valsartan for treatment of heart failure patients with reduced ejection fraction and New York Heart Association class II-IV symptoms following a large, Phase III clinical trial (PARADIGM-HF) that demonstrated a 20% reduction in the combined primary end-point of death from cardiovascular cause or hospitalization for heart failure compared to enalapril. Areas covered: This review discusses the clinical efficacy and safety of angiotensin receptor neprilysin inhibitor sacubitril-valsartan in heart failure with reduced ejection fraction. Expert opinion: Based on the PARADIGM-HF trial, sacubitril-valsartan offers compelling reductions in meaningful clinical endpoints, independent of age or severity of disease. The rate of adverse events was comparable between the enalapril and sacubitril-valsartan groups, although the absolute rates are likely underestimated due to the entry criteria and run-in period. Future trials and post-market surveillance are critical to better understand the risk of angioedema in high risk populations, particularly African-Americans, as well as long-term theoretical risks including the potential for increased cerebral amyloid plaque deposition with possible development of neurocognitive disease. Current trials are underway to evaluate potential benefit in patients with heart failure with preserved ejection fraction.
Ca2+‐NFATc1 signaling is an essential axis of osteoclast differentiation

Summary: Osteoclasts are unique, multinucleated giant cells that decalcify and degrade the bone matrix. They originate from hematopoietic cells and their differentiation is dependent on a tumor necrosis factor (TNF) family cytokine, receptor activator of nuclear factor‐κB (NF‐κB) ligand (RANKL), as well as macrophage‐colony stimulating factor (M‐CSF). Recent studies have unveiled the precise molecular mechanism underlying osteoclastogenesis. In particular, the discovery of nuclear factor of activated T cells c1 (NFATc1), the master regulator of osteoclastogenesis, has proven to be a breakthrough in this field. NFATc1 is activated by Ca2+ signaling induced by the activation of the immunoglobulin‐like receptor signaling associated with immunoreceptor tyrosine‐based activation motif (ITAM)‐harboring adapters. The long‐lasting Ca2+ oscillation, which is evident during osteoclastogenesis, may ensure the robust induction of NFATc1 through an autoamplification mechanism. Thus, intracellular Ca2+ is a critical attribute of osteoclastogenic signaling. In addition, osteoclasts are exposed to a very high extracellular Ca2+ concentration ([Ca2+]o) in the bone microenvironment and respond to the change in [Ca2+]o by increasing the intracellular Ca2+, which regulates diverse cellular functions. Investigation of the molecular mechanisms underlying the regulation of intracellular Ca2+ dynamics may open up new directions for therapeutic strategies in bone disease.
Importance and mechanism of ‘switch’ function of SAP family adapters

Summary: The signaling lymphocytic activation molecule (SLAM)‐associated protein (SAP) family of adapters includes SAP, Ewing’s sarcoma‐associated transcript‐2 (EAT‐2), and EAT‐2‐related transducer (ERT). These Src homology‐2 (SH2) domain‐only molecules play critical roles in immune regulation. The prototype of the SAP family, SAP, is mutated in X‐linked lymphoproliferative disease in humans. Moreover, genetically engineered mice lacking one or more SAP family members have defects in multiple immune cell types including T cells, natural killer (NK) cells, NKT cells, and B cells. Accumulating data show that SAP family adapters regulate immunity by influencing the functions of SLAM family receptors, through two distinct but cooperative mechanisms. First, SAP family adapters couple SLAM family receptors to active biochemical signals, which promote immune cell functions. Second, SAP family adapters interfere with the intrinsic ability of SLAM family receptors to trigger inhibitory signals, which could be mediated via molecules such as SH2 domain‐containing 5′‐inositol phosphatase‐1. The latter effect of SAP family adapters does not seem to be because of direct blocking of inhibitory effector binding to SLAM family receptors. Rather, it appears to implicate alternative mechanisms such as functional competition, trans‐regulation, or steric hindrance. In the absence of SAP family adapters, the inhibitory signals mediated by SLAM family receptors suppress critical activating receptors, explaining in part the pronounced phenotypes seen in SAP family adapter‐deficient humans and mice. Thus, SAP family adapters are molecular switches that regulate immunity as a result of their capacity to control the type of signals and functions emanating from SLAM family receptors.
The safety of available treatments options for neuroendocrine tumors

ABSTRACT Introduction: Neuroendocrine neoplasms (NEN) represent a heterogeneous group of malignancies generally characterized by low proliferation and indolent course. However, about half of the newly diagnosed cases are metastatic and require long-term systemic therapies. Areas covered: This review revises the literature to summarize the current knowledge upon safety of all systemic treatment options available. Thirty three different clinical studies have been considered, including 4 on somatostatin analogues (SSA), 5 on targeted therapies, 10 on peptide receptor radionuclide therapy (PRRT), and 14 on chemotherapy. Expert opinion: SSA are safe and well tolerated without any relevant severe adverse event and very low treatment discontinuation rate. Targeted therapies show a satisfying safety profile. Most adverse events are grade 1–2 and easy manageable with dose reduction or temporary interruption. PRRT is manageable and safe with a low rate of grade 3–4 adverse events. However, severe renal and hematologic toxicity may occur. Chemotherapy is usually considered after previous therapeutic lines. Therefore, these subjects are more susceptible to experience adverse events due to cumulative toxicities or poor performance status. The available systemic treatment options are generally well tolerated and suitable for long-term administration. Cumulative toxicity should be taken in account for the definition of therapeutic sequence.
Satiety signals and obesity

Purpose of reviewThe obesity epidemic over the world has called to attention different ways to manage this development. As bariatric surgery today is the only manner by which rapid and sustained weight control can be achieved, new ways of treating obesity are under investigation. This review focuses on today's knowledge on satiety signaling as a means to combat obesity. Recent findingsThe combined knowledge achieved from obesity surgery with gastric bypass and duodenal switch together with the pharmacological treatment of type 2 diabetes have given us some clues of how to manage obesity. The basis for our understanding is the present research focusing on the gut peptide hormones that are released in response to food intake, and the paucity of satiety signaling seems to prevail in obesity. This means that obese patients experience less activation of higher brain centers in association with a meal and therefore compensate with increased meal size or frequent food intake. SummaryAltered satiety signaling primarily emanating from the gastrointestinal tract seems to lead to the development of obesity and type 2 diabetes. Pharmacological tools that enhance the gut hormone signaling are in focus for the upcoming venues of treatment.
Changes of Anterior Chamber Depth and Angle After Cataract Surgery Measured by Anterior Segment OCT

Purpose: To report the change of anterior chamber parameters according to cataract severity after cataract surgery and to determine its relationship to the severity of cataract by using anterior segment optical coherence tomography. Methods: We measured the anterior chamber parameters in 19 eyes of 14 patients before, 1 week after, and 1 month after cataract surgery by slit lamp-adapted optical coherence tomography (SL-OCT). The measured parameters were as follows : the anterior chamber depth (ACD), the angle-opening distance 250 μm from the scleral spur (AOD250), the angle-opening distance 500 μm from the scleral spur (AOD500), and the trabecular-iris angle (TIA). We analyzed the relationship between the severity of cataract and the change of the anterior chamber parameters. Results: The ACD, AOD250, AOD500, and TIA increased significantly at postoperative 1 week (P=0.000, 0.002, 0.005, 0.022) and 1 month (P=0.000, 0.004, 0.001, 0.002). The preoperative parameters were negatively correlated with the differences between the postoperative 1 week and preoperative parameters (γ=-0.834, -0.591, -0.421, -0.826) and between postoperative 1 month and preoperative parameters (γ=-0.659, -0.700, -0.770, -0.821). The change of parameters at postoperative 1 week (by N P=0.959, 0.916, 0.824, 1.000, by C P=0.454, 0.665, 0.578, 0.578) and 1 month (by N P=0.858, 0.973, 0.959, 0.959, by C P=0.999, 0.207, 0.950, 0.981) were not significantly different according to the severity of cataract (N, C). Conclusions: Our results showed that cataract surgery significantly deepened the anterior chamber and widened its angle. The shallower and narrower the preoperative anterior chamber depth and angle were, respectively, the greater the postoperative changes of anterior chamber depth and angle were.
Cardiovascular outcomes of patients with rheumatoid arthritis prescribed disease modifying anti-rheumatic drugs: a review

ABSTRACT Introduction: Rheumatoid arthritis (RA) is associated with a heightened risk of cardiovascular disease (CVD), with both traditional CV risk factors and inflammation contributing to this risk. Areas covered: This review highlights the burden of CVD in RA and associated traditional CV risk factors, including the complexity of dyslipidemia in RA and the so-called ‘lipid paradox. ’ Furthermore, the recognized RA-disease-specific factors associated with higher risk of CVD and the role of systemic inflammation in the pathogenesis of CVD in RA will be addressed. With the advent of biologic and targeted synthetic therapies in the treatment of RA, the effect of conventional and newer generation disease modifying anti-rheumatic therapies (DMARDs) on CV risk and associated risk factors will also be discussed. Expert opinion: Identifying the RA phenotype at greatest risk of CVD, understanding the interplay of increased traditional risk factors, common inflammatory processes and RA-specific factors, and personalized use of DMARDs according to disease phenotype and comorbidity to reduce this risk are key areas for future research.
Intrinsic and extrinsic control of peripheral T‐cell tolerance by costimulatory molecules of the CD28/ B7 family

Summary: Positive and negative costimulation by members of the CD28 family is critical for the development of productive immune responses against foreign pathogens and their proper termination to prevent inflammation‐induced tissue damage. In addition, costimulatory signals are critical for the establishment and maintenance of peripheral tolerance. This paradigm has been established in many animal models and has led to the development of immunotherapies targeting costimulation pathways for the treatment of cancer, autoimmune disease, and allograft rejection. During the last decade, the complexity of the biology of costimulatory pathways has greatly increased due to the realization that costimulation does not affect only effector T cells but also influences regulatory T cells and antigen‐presenting cells. Thus, costimulation controls T‐cell tolerance through both intrinsic and extrinsic pathways. In this review, we discuss the influence of costimulation on intrinsic and extrinsic pathways of peripheral tolerance, with emphasis on members of the CD28 family, CD28, cytotoxic T‐lymphocyte antigen‐4 (CTLA‐4), and programmed death‐1 (PD‐1), as well as the downstream cytokine interleukin‐1 (IL‐2).
Non‐canonical NF‐κB signaling activation and regulation: principles and perspectives

Summary: Nuclear‐factor κB (NF‐κB) transcription factors are activated by a wide variety of stimuli in diverse cell types and control key aspects of immune function and development. Receptor‐mediated activation of NF‐κB appears to occur through two distinct signaling pathways termed as the canonical and non‐canonical NF‐κB pathways. Although much work has demonstrated the physiological importance of non‐canonical NF‐κB signaling to immunity and its involvement in diverse pathologies, such as cancers and autoimmune disease, the architecture and regulation of the pathway is only beginning to be understood. The non‐canonical pathway appears to be activated by a select set of receptors within the tumor necrosis factor superfamily, and we discuss the molecular mechanisms that connect ligation of these receptors to pathway activation. It has become increasingly clear that the key regulatory step of the pathway involves modulation of the post‐translational degradation of NF‐κB‐inducing kinase (NIK), the central activating kinase of non‐canonical NF‐κB signaling. How NIK post‐translational stability is controlled before and after receptor ligation is an important aspect of understanding non‐canonical NF‐κB signaling. Furthermore, how release of NF‐κB dimers downstream of the pathway’s activation is actually connected to its identified physiological and pathological roles is a key remaining question in the field.
How I diagnose and treat neutropenia

Purpose of reviewNeutropenia absolute neutrophil count (ANC) less than 1.5 × 109/l is a common hematological finding, and severe neutropenia, that is, ANC less than 0.5 × 109/l is a well known risk factor for susceptibility to bacterial infections. This review provides a succinct clinical approach to the diagnosis and treatment of neutropenia with specific recommendations on the treatment of severe chronic neutropenia with the myeloid growth factor, granulocyte colony-stimulating factor (G-CSF). Recent findingsExperts agree that patients with acute febrile neutropenia should be treated with antibiotics and that patients at high risk of severe neutropenia (>20% risk) after myelosuppressive chemotherapy should be treated prophylactically with a myeloid growth factor, usually G-CSF. The diversity of causes and consequences of chronic neutropenia make the diagnosis and management of these patients more complicated. SummaryThe review provides a stepwise approach to neutropenia focusing first on reaching a provisional diagnosis and treatment plan then steps to a final diagnosis. It also provides specific recommendations on the treatment of severe chronic neutropenia with G-CSF.
Dimer‐specific regulatory mechanisms within the NF‐κB family of transcription factors

Summary: A fundamental feature of the transcriptional response to an nuclear factor‐κB (NF‐κB)‐inducing stimulus is that the response is highly selective and limited to the activation of only a subset of potential NF‐κB target genes. One major contributor to selectivity of the response is likely to be the capacity of different NF‐κB dimers to regulate different sets of target genes. The NF‐κB family of transcription factors consists of five proteins, RelA, c‐Rel, RelB, p50, and p52, which assemble into several homodimeric and heterodimeric species. Studies of mutant mouse strains have revealed that each family member, and perhaps each dimer, carries out unique functions in regulating transcription in cells of the immune system and in many other cell types. Dimer‐specific functions can be conferred by selective protein–protein interactions with other transcription factors, coregulatory proteins, and chromatin proteins. Unique DNA‐binding specificities and affinities make additional contributions to selectivity of the response, with growing evidence that some NF‐κB dimers can adopt different conformations and thereby function differently when bound to different DNA sequences. Despite significant advances, our knowledge remains limited and many years of additional work will be needed to fully understand how the dimer‐specific functions of NF‐κB contribute to transcriptional selectivity.