Miracle-dz/UniFAR-FTUs huggingface dataset:
Incipient and Subclinical Tuberculosis: a Clinical Review of Early Stages and Progression of Infection

SUMMARY Tuberculosis (TB) is the leading infectious cause of mortality worldwide, due in part to a limited understanding of its clinical pathogenic spectrum of infection and disease. Historically, scientific research, diagnostic testing, and drug treatment have focused on addressing one of two disease states: latent TB infection or active TB disease. Recent research has clearly demonstrated that human TB infection, from latent infection to active disease, exists within a continuous spectrum of metabolic bacterial activity and antagonistic immunological responses. This revised understanding leads us to propose two additional clinical states: incipient and subclinical TB. The recognition of incipient and subclinical TB, which helps divide latent and active TB along the clinical disease spectrum, provides opportunities for the development of diagnostic and therapeutic interventions to prevent progression to active TB disease and transmission of TB bacilli. In this report, we review the current understanding of the pathogenesis, immunology, clinical epidemiology, diagnosis, treatment, and prevention of both incipient and subclinical TB, two emerging clinical states of an ancient bacterium.
Mortality due to cirrhosis and liver cancer in the United States, 1999-2016: observational study

Abstract Objective To describe liver disease related mortality in the United States during 1999-2016 by age group, sex, race, cause of liver disease, and geographic region. Design Observational cohort study. Setting Death certificate data from the Vital Statistics Cooperative, and population data from the US Census Bureau compiled by the Center for Disease Control and Prevention’s Wide-ranging Online Data for Epidemiologic Research (1999-2016). Participants US residents. Main outcome measure Deaths from cirrhosis and hepatocellular carcinoma, with trends evaluated using joinpoint regression. Results From 1999 to 2016 in the US annual deaths from cirrhosis increased by 65%, to 34 174, while annual deaths from hepatocellular carcinoma doubled to 11 073. Only one subgroup—Asians and Pacific Islanders—experienced an improvement in mortality from hepatocellular carcinoma: the death rate decreased by 2.7% (95% confidence interval 2.2% to 3.3%, P<0.001) per year. Annual increases in cirrhosis related mortality were most pronounced for Native Americans (designated as “American Indians” in the census database) (4.0%, 2.2% to 5.7%, P=0.002). The age adjusted death rate due to hepatocellular carcinoma increased annually by 2.1% (1.9% to 2.3%, P<0.001); deaths due to cirrhosis began increasing in 2009 through 2016 by 3.4% (3.1% to 3.8%, P<0.001). During 2009-16 people aged 25-34 years experienced the highest average annual increase in cirrhosis related mortality (10.5%, 8.9% to 12.2%, P<0.001), driven entirely by alcohol related liver disease. During this period, mortality due to peritonitis and sepsis in the setting of cirrhosis increased substantially, with respective annual increases of 6.1% (3.9% to 8.2%) and 7.1% (6.1% to 8.4%). Only one state, Maryland, showed improvements in mortality (−1.2%, −1.7% to −0.7% per year), while many, concentrated in the south and west, observed disproportionate annual increases: Kentucky 6.8% (5.1% to 8.5%), New Mexico 6.0% (4.1% to 7.9%), Arkansas 5.7% (3.9% to 7.6%), Indiana 5.0% (3.8% to 6.1%), and Alabama 5.0% (3.2% to 6.8%). No state showed improvements in hepatocellular carcinoma related mortality, while Arizona (5.1%, 3.7% to 6.5%) and Kansas (4.3%, 2.8% to 5.8%) experienced the most severe annual increases. Conclusions Mortality due to cirrhosis has been increasing in the US since 2009. Driven by deaths due to alcoholic cirrhosis, people aged 25-34 have experienced the greatest relative increase in mortality. White Americans, Native Americans, and Hispanic Americans experienced the greatest increase in deaths from cirrhosis. Mortality due to cirrhosis is improving in Maryland but worst in Kentucky, New Mexico, and Arkansas. The rapid increase in death rates among young people due to alcohol highlight new challenges for optimal care of patients with preventable liver disease.
Systematic review and meta-analysis of the negative outcomes of retinopathy of prematurity treated with laser photocoagulation

Introduction: Retinopathy of prematurity is a leading cause of potentially avertable childhood blindness around the world. And laser photocoagulation is currently performed as a gold standard for retinopathy of prematurity treatment, but it may contribute to elevated myopia and decreased visual field. Therefore, the objective of this meta-analysis is to explore the negative impact of laser photocoagulation for retinopathy of prematurity in terms of anatomic outcomes and structural outcomes. Methods: Studies were retrieved through literature searches in PubMed and EMBASE from 1990 to 2017 in English. Case-control studies that reported anatomic and structural changes or significant complications after laser coagulation or cryotherapy for retinopathy of prematurity were eligible. Results: This meta-analysis included eight original studies related to laser treatment for retinopathy of prematurity at any stages. A total of 1422 infants were participated, of which 1156 documented subthreshold or threshold retinopathy of prematurity without laser treatment were selected as comparison group and the rest treated with diode or argon laser coagulation were chosen for experiment group. Taking all included studies into account, spherical equivalent (mean difference −2.53, 95% confidence interval: –5.23 to 0.18, I2 = 96%, P < 0.00001), anterior chamber depth (mean difference −0.52, 95% confidence interval: −0.76 to −0.28, I2 = 55%, P = 0.11), astigmatism (odds ratio 3.19, 95% confidence interval: 1.61 to 6.32, I2 = 0%, P = 0.54), and myopia (odds ratio 8.08, 95% confidence interval: 3.79 to 17.23, I2 = 37%, P = 0.21) were associated with laser treatment for retinopathy of prematurity. Axial length (mean difference −0.01, 95% confidence interval: –0.28 to 0.27, I2 = 0%, P = 0.62) and anisometropia (odds ratio 4.21, 95% confidence interval: 0.54 to 33.17, I2 = 1%, P = 0.31) had no statistical significance on laser coagulation for retinopathy of prematurity. Conclusion: This meta-analysis showed that spherical equivalent, anterior chamber depth, astigmatism, and myopia were associated with the negative outcomes of laser coagulation, while axial length and anisometropia had no statistical importance on the defects of laser coagulation. Therefore, patients treated with laser coagulation should follow periodic cycloplegic refraction and receive early optical correction.
The osteology of Periptychus carinidens: A robust, ungulate-like placental mammal (Mammalia: Periptychidae) from the Paleocene of North America

Periptychus is the archetypal genus of Periptychidae, a clade of prolific Paleocene ‘condylarth’ mammals from North America that were among the first placental mammals to radiate after the end-Cretaceous extinction, remarkable for their distinctive dental anatomy. A comprehensive understanding of the anatomy of Periptychus has been hindered by a lack of cranial and postcranial material and only cursory description of existing material. We comprehensively describe the cranial, dental and postcranial anatomy of Periptychus carinidens based on new fossil material from the early Paleocene (Torrejonian) of New Mexico, USA. The cranial anatomy of Periptychus is broadly concurrent with the inferred plesiomorphic eutherian condition, albeit more robust in overall construction. The rostrum is moderately elongate with no constriction, the facial region is broad, and the braincase is small with a well-exposed mastoid on the posterolateral corner and tall sagittal and nuchal crests. The dentition of Periptychus is characterized by strongly crenulated enamel, enlarged upper and lower premolars with a tall centralised paracone/protoconid. The postcranial skeleton of Periptychus is that of a robust, medium-sized (~20 Kg) stout-limbed animal that was incipiently mediportal and adopted a plantigrade stance. The structure of the fore- and hindlimb of Periptychus corresponds to that of a typically terrestrial mammal, while morphological features of the forelimb such as the low tubercles of the humerus, long and prominent deltopectoral crest, pronounced medial epicondyle, and hemispherical capitulum indicate some scansorial and/or fossorial ability. Most striking is the strongly dorsoplantarly compressed astragalus of Periptychus, which in combination with the distal crus and calcaneal morphology indicates a moderately mobile cruropedal joint. The anatomy of Periptychus is unique and lacks any extant analogue; it combines a basic early placental body plan with numerous unique specializations in its dental, cranial and postcranial anatomy that exemplify the ability of mammals to adapt and evolve following catastrophic environmental upheaval.
An accelerated nonlocal Poisson‐Boltzmann equation solver for electrostatics of biomolecule

The nonlocal modified Poisson‐Boltzmann equation (NMPBE) is one important variant of a commonly used dielectric continuum model, the Poisson‐Boltzmann equation (PBE), for computing electrostatics of biomolecules. In this paper, an accelerated NMPBE solver is constructed by finite element and finite difference hybrid techniques. It is then programmed as a software package for computing electrostatic solvation and binding free energies for a protein in a symmetric 1:1 ionic solvent. Numerical results validate the new solver and its numerical stability. They also demonstrate that the new solver has much better performance than the corresponding finite element solver in terms of computer CPU time. Furthermore, they show that the binding free energies produced by NMPBE can match chemical experiment data better than those by PBE.
Calmodulin: A Multitasking Protein in Kv7.2 Potassium Channel Functions

The ubiquitous calcium transducer calmodulin (CaM) plays a pivotal role in many cellular processes, regulating a myriad of structurally different target proteins. Indeed, it is unquestionable that CaM is the most relevant transductor of calcium signals in eukaryotic cells. During the last two decades, different studies have demonstrated that CaM mediates the modulation of several ion channels. Among others, it has been indicated that Kv7.2 channels, one of the members of the voltage gated potassium channel family that plays a critical role in brain excitability, requires CaM binding to regulate the different mechanisms that govern its functions. The purpose of this review is to provide an overview of the most recent advances in structure–function studies on the role of CaM regulation of Kv7.2 and the other members of the Kv7 family.
The effect of growth rate on the three‐dimensional orientation of vascular canals in the cortical bone of broiler chickens

Vascular canals in cortical bone during growth and development typically show an anisotropic pattern with canals falling into three main categories: circumferential, radial, and longitudinal. Two major hypotheses attempt to explain the preferred orientations in bone: that vascular canal orientation is optimized to resist a predominant strain direction from functional loading, or that it reflects growth requirements and velocity. We use a controlled growth experiment in broiler chickens to investigate the effect of growth rate on vascular canal orientation. Using feed restriction we set up a fast growing control group and a slow growing restricted group. We compared the microstructure in the humerus and the femur at 42 days of age using synchrotron micro‐computed tomography (micro‐CT), a three‐dimensional (3D) method that visualizes the full canal network. We measured the 3D orientation of each canal in the whole cross‐section of the bone cortex using a set of custom ImageJ scripts. Using these orientations we compute laminar, radial, and longitudinal indices that measure the proportion of circumferential, radial, and longitudinal canals, by unit of length, in the cortex. Following previous studies we hypothesized that vascular canal orientation is related to growth, with radial canals linked to a faster growth rate and related to functional loading through a high laminar index in flight bones which reflects torsional loading resulting from active flight. The control group had final body weights that were nearly twice the final weights of the restricted group and higher absolute growth rates. We found consistent patterns in the comparison between the humerus and the femur in both groups, with the humerus having higher laminar and longitudinal indices, and a lower radial index than the femur. The control group had higher radial indices and lower laminar and longitudinal indices in both the humerus and the femur than the restricted group. The higher radial indices in our control group point to a link between radial canals and faster growth, and between laminar canals and slower growth, while the higher laminar indices in the humerus point to a link between circumferential canals and torsional loading. Overall, our results indicate that the orientation of the cortical canal network in a bone is the consequence of a complex interaction between the growth rate of that bone and functional loading environment.
Prognostic implication of monocytes in atrial fibrillation: The West Birmingham Atrial Fibrillation Project

Background and objectives High monocyte counts are related to adverse outcomes in cardiovascular disease. Their role in prognostication in patients with atrial fibrillation (AF) is unknown. We investigated whether monocyte counts are useful as a marker of prognosis in patients with AF. Methods Monocyte counts were obtained from blood samples in 881 AF patients. Study outcomes were (i) all-cause death; (ii) major adverse cardiovascular events; (iii) stroke, TIA or other systemic embolism (SSE); and (iv) major bleeding. Results Median follow up was 7.2 years; 44% of patients died, 48% developed MACE; 9% had SSE and 5% had major bleeding. On Cox regression, after adjustment for CHA2DS2-VASc score, the highest quartile of monocyte counts (i.e., ≥580 μL vs. other quartiles) was associated with increased risk of death (hazard ratio [HR] 1.64, 95% confidence interval [CI] 1.31–2.05, p<0.001) and MACE (HR 1.58, 95% CI 1.28–1.96, p<0.001). Persistent monocyte levels ≥580 per μL during follow up were associated with further increase in risk of death (HR 1.52, 95% CI 1.10–2.11, p = 0.01) and MACE (HR 1.54, 95% CI 1.13–2.09, p = 0.006). Persistent monocyte levels ≥580 per μL during were associated with a significant increase in major bleeding events (HR 2.77, 95% CI 1.36–5.67, p = 0.005, after adjustment for HAS-BLED score). Conclusion High monocyte counts independently predict the occurrence of MACE, major bleeding and mortality, but not SSE. Understanding the pathophysiological mechanisms involved would help understand the relationships between monocytes, and adverse thrombotic and bleeding outcomes in AF patients.
Psychological constraints on string-based methods for pattern discovery in polyphonic corpora

Researchers often divide symbolic music corpora into contiguous sequences of n events (called n-grams) for the purposes of pattern discovery, key finding, classification, and prediction. What is more, several studies have reported improved task performance when using psychologically motivated weighting functions, which adjust the count to privilege n-grams featuring more salient or memorable events (e.g., Krumhansl, 1990). However, these functions have yet to appear in harmonic pattern discovery algorithms, which attempt to discover the most recurrent chord progressions in complex polyphonic corpora. This study examines whether psychologically-motivated weighting functions can improve harmonic pattern discovery algorithms. Models using various n-gram selection methods, weighting functions, and ranking algorithms attempt to discover the most conventional closing harmonic progression in the common-practice period, ii6-"I64"-V7-I, with the progression's mean reciprocal rank serving as an evaluation metric for model comparison.
A home but how to connect with others? A qualitative meta‐synthesis of experiences of people with mental illness living in supported housing

Supported housing principles emphasise the importance of decent, stable and affordable housing, and the provision of individualised support to enable people experiencing mental illness to live in their preferred communities, and to recover. This study sought to synthesise qualitative research addressing the question: how does living in supported housing facilitate social connections and participation from the viewpoints of people living with mental illness? Three databases (CINAHL, PsycINFO, Medline) were systematically searched to identify 19 peer-reviewed reports on 17 studies published during 2001-2016, in which the views and experiences of supported housing residents with mental illness were reported. Most studies were informed by grounded theory and used interview methods. Appraisal indicated the reports were of varying quality, but all met the inclusion criterion of reporting qualitative data relevant to the research question. Constant comparative methods were used to synthesise the reported data, and to identify themes across the studies. There were four overarching themes regarding the lived experience of supported housing for people with mental illness: (a) living in supported housing gave individuals privacy, a sense of control, stability and security; (b) stable housing supported residents' confidence to rebuild an identity and meaning in life, (c) there is a delicate balance between appreciating privacy and dealing with loneliness, and (d) opportunities and support to reconnect with families, friends and community are valued. The meta-synthesis findings highlight that supported housing residents face challenges of protecting their privacy and being lonely when on their own. Individualised support approaches need to attend to personal preferences for social participation and their varied meanings and significance. Further research is required to better understand how individualised forms of support can enable supported housing residents to connect with family, friends and community in their preferred ways.
Softening the Stressed Giant Titin in Diabetes Mellitus.

Abnormal left ventricular (LV) relaxation and increased diastolic stiffness are important features of heart failure with preserved ejection fraction (HFpEF); the 2 major contributors to LV diastolic function are the cardiomyocytes and the extracellular matrix.1 Cardiomyocytes govern LV relaxation and are a determinant of LV chamber distensibility. Increased cardiomyocyte stiffness can be caused by sarcomeric myofilaments; the focus of the work by Hopf et al2 is on the role of the myofilament titin, a major contributor to diastolic stiffening in HFpEF.3,4 Approximately 1/3 of HFpEF patients have diabetes mellitus (DM), and Hopf et al2 provide important insights in the insulin-related signaling pathways that modify titin’s stiffness in HFpEF patients with DM. Article, see p 342 The extensible I-band region of titin comprises (1) tandem immunoglobulins segments, (2) the PEVK (proline-glutamic acid-valine-lysine-rich element), and (3) the N2B-Us (a unique sequence [Us] that is part of the N2B element). 5 Titin’s stiffness can be modulated through differential mRNA splicing that gives rise to stiff and compliant titin isoforms.6 Upregulation of compliant isoforms occurs in pathological conditions, presumably to counteract fibrosis.7 Upregulating compliant titin can be experimentally accomplished by targeting RBM20 (RNA-binding motif protein 20), and this normalizes titin’s stiffness in models with diastolic dysfunction.8,9 Posttranslational modification of titin also alters titin’s stiffness.10 S4010 and S4099 in N2B-Us can be phosphorylated, resulting in a reduction of titin stiffness, whereas phosphorylation of the S11878 and S12022, located in the PEVK segment, results in increased stiffness. Previous studies have shown that increased cardiomyocyte stiffness in DM is a consequence of deranged titin phosphorylation, but the pathways connecting insulin deficiency to altered titin phosphorylation have not been established. Hopf et al2 shed light on the signaling pathways involved and, importantly, provide potential therapeutic …
Objective assessment of obstructive sleep apnea in normal pregnant and preeclamptic women

ABSTRACT Objective: Obstructive sleep apnea (OSA) is a risk factor for adverse pregnancy outcomes. The aim of this study was to evaluate the association between OSA and preeclampsia. Methods: Between 30 and 39 weeks gestation, objective sleep apnea were evaluated in 38 normal pregnant and 40 preeclamptic women. Preeclampsia was defined by having a blood pressure (BP) > 140/90 mmHg on two occasions after the 20th week of pregnancy with excess protein in the urine (> 300 mg in 24 h) or 30 mg persistent proteinuria (+ 1 in dipsticks) in random samples. Objective sleep apnea was evaluated using an overnight in-hospital sleep evaluation using the SOMNOwatch plus Respiratory Screener. OSA was defined as an apnea–hypopnea index (AHI) ≥ 5, and further grouped into severity categories: mild (5–14.9), moderate (15–29.9), and severe (≥ 30). Results: Mean AHI was 33.3 ± 12.1 in preeclamptic women and was 23.8 ± 15.8 in normal pregnant women (p = 0.008). There was significant difference in prevalence of OSA severity (none, mild, moderate, or severe) between groups. Out of 33 preeclamptic women, 11 women had moderate and 22 women had severe OSA. Whereas, among 33 normal pregnant women, 8, 13, and10 women had mild, moderate, and severe OSA, respectively. Two normal pregnant women had no OSA (AHI< 5). Conclusion: Our study suggests women are susceptible to developing OSA during pregnancy that is associated with an increased risk of preeclampsia.
Inhibiting Glycogen Synthase Kinase 3 Reverses Obesity-Induced White Adipose Tissue Inflammation by Regulating Apoptosis Inhibitor of Macrophage/CD5L-Mediated Macrophage Migration

Objective— Obesity-induced inflammation in white adipose tissue, characterized by increased macrophage infiltration and associated with macrophage population shift from anti-inflammatory M2 to proinflammatory M1 macrophages, largely contributes to obesity-induced insulin resistance and influences type 2 diabetes mellitus pathogenesis. GSK3 (glycogen synthase kinase 3), a serine/threonine kinase, has been reported to participate in various cellular processes. We sought to examine the potential mechanism by which GSK3, a serine/threonine kinase implicated in various cellular processes, modulates obesity-induced visceral adipose tissue (VAT) inflammation. Approach and Results— Male C57BL/6J mice were fed a high-fat diet for 10 weeks while being treated with vehicle control or GSK3 inhibitors SB216763 or CHIR99021. RNA-sequencing results using VAT demonstrated that GSK3 inhibitor treatment reversed obesity-specific expression of genes associated with inflammation. Consistently, GSK3 inhibition reduced obesity-induced VAT inflammation as characterized by decreased proinflammatory M1 macrophages but increased anti-inflammatory M2 macrophages in the VAT and reduced circulatory inflammatory monocytes. These anti-inflammatory effects of GSK3 inhibition were found to be driven, at least in part, by inhibiting production of apoptosis inhibitor of macrophage in macrophages via inactivating STAT3 to reduce free fatty acid and chemokine level produced from VAT to suppress the migration/chemotaxis of macrophages and monocytes. Conclusions— Our findings suggest that GSK3 may act as an important regulator of obesity-induced inflammation and characterize the novel role of GSK3 in shifting macrophage polarization and reinforce its therapeutic potential for obesity-induced inflammation and its associated diabetes mellitus.