Miracle-dz/UniFAR-FTUs huggingface dataset:
Osteoarthritis, Osteophytes, and Enthesophytes Affect Biomechanical Function in Adults With X-linked Hypophosphatemia

Abstract Context X-Linked hypophosphatemia (XLH) is a lifelong metabolic disease with musculoskeletal comorbidities that dominate the adult clinical presentation. Objective The adult XLH disorder has yet to be quantified on the basis of the physical and functional limitations that can affect activities of daily living. Our goal was to report the impact of the musculoskeletal manifestations on physical function. Design and setting Musculoskeletal function was evaluated by validated questionnaires and in an interdisciplinary clinical space where participants underwent full-body radiologic imaging, goniometric range of motion (ROM) measurements, general performance tests, and kinematic gait analysis. Patients Nine adults younger than 60 years with a diagnosis of XLH and self-reported musculoskeletal disability, but able to independently ambulate, were selected to participate. Passive ROM and gait analysis were also performed on age-approximated controls to account for differences between individual laboratory instrumentation. Results Enthesophytes, degenerative arthritis, and osteophytes were found to be consistently bilateral and diffusely present at the spine and synovial joints across participants, with predominance at weight-bearing joints. Passive ROM in adults with XLH was decreased at the cervical spine, hip, knee, and ankle compared to controls. Gait analysis relative to controls revealed increased step width, markedly increased lateral trunk sway, and physical restriction at the hip, knees, and ankle joints that translated into limitations through the gait cycle. Conclusions The functional impact of XLH musculoskeletal comorbidities supports the necessity for creating an interprofessional health-care team with the goal of establishing a longitudinal plan of care that considers the manifestations of XLH across the lifespan.
Implications of Selective Autophagy Dysfunction for ALS Pathology

Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disorder that progressively affects motor neurons in the brain and spinal cord. Due to the biological complexity of the disease, its etiology remains unknown. Several cellular mechanisms involved in the neurodegenerative process in ALS have been found, including the loss of RNA and protein homeostasis, as well as mitochondrial dysfunction. Insoluble protein aggregates, damaged mitochondria, and stress granules, which contain RNA and protein components, are recognized and degraded by the autophagy machinery in a process known as selective autophagy. Autophagy is a highly dynamic process whose dysregulation has now been associated with neurodegenerative diseases, including ALS, by numerous studies. In ALS, the autophagy process has been found deregulated in both familial and sporadic cases of the disease. Likewise, mutations in genes coding for proteins involved in the autophagy machinery have been reported in ALS patients, including selective autophagy receptors. In this review, we focus on the role of selective autophagy in ALS pathology.
Monocarboxylate Transporter 4 Regulates Glioblastoma Motility and Monocyte Binding Ability

Glioblastoma (GBM) is characterized by severe hypoxic and acidic stress in an abnormal microenvironment. Monocarboxylate transporter (MCT)4, a pH-regulating protein, plays an important role in pH homeostasis of the glycolytic metabolic pathways in cancer cells. The present study showed that GBM exposure to hypoxic conditions increased MCT4 expression. We further analyzed the glioma patient database and found that MCT4 was significantly overexpressed in patients with GBM, and the MCT4 levels positively correlated with the clinico-pathological grades of gliomas. We further found that MCT4 knockdown abolished the hypoxia-enhanced of GBM cell motility and monocyte adhesion. However, the overexpression of MCT4 promoted GBM cell migration and monocyte adhesion activity. Our results also revealed that MCT4-regulated GBM cell motility and monocyte adhesion are mediated by activation of the serine/threonine-specific protein kinase (AKT), focal adhesion kinase (FAK), and epidermal growth factor receptor (EGFR) signaling pathways. Moreover, hypoxia mediated the acetylated signal transducer and activator of transcription (STAT)3 expression and regulated the transcriptional activity of hypoxia inducible factor (HIF)-1α in GBM cell lines. In a GBM mouse model, MCT4 was significantly increased in the tumor necrotic tissues. These findings raise the possibility for the development of novel therapeutic strategies targeting MCT4.
Precision medicine and actionable alterations in lung cancer: A single institution experience

Objectives Oncology has become more reliant on new testing methods and a greater use of electronic medical records, which provide a plethora of information available to physicians and researchers. However, to take advantage of vital clinical and research data for precision medicine, we must initially make an effort to create an infrastructure for the collection, storage, and utilization of this information with uniquely designed disease-specific registries that could support the collection of a large number of patients. Materials and methods In this study, we perform an in-depth analysis of a series of lung adenocarcinoma patients (n = 415) with genomic and clinical data in a recently created thoracic patient registry. Results Of the 415 patients with lung adenocarcinoma, 59% (n = 245) were female; the median age was 64 (range, 22–92) years with a median OS of 33.29 months (95% CI, 29.77–39.48). The most common actionable alterations were identified in EGFR (n = 177/415 [42.7%]), ALK (n = 28/377 [7.4%]), and BRAF V600E (n = 7/288 [2.4%]). There was also a discernible difference in survival for 222 patients, who had an actionable alteration, with a median OS of 39.8 months as compared to 193 wild-type patients with a median OS of 26.0 months (P<0.001). We identified an unprecedented number of actionable alterations [53.5% (222/415)], including distinct individual alteration rates, as compared with 15.0% and 22.3% in TCGA and GENIE respectively. Conclusion The use of patient registries, focused genomic panels and the appropriate use of clinical guidelines in community and academic settings may influence cohort selection for clinical trials and improve survival outcomes.
Metabolism of bioconjugate therapeutics: why, when, and how?

Abstract Bioconjugation of therapeutic agents has been used as a selective drug delivery platform for many therapeutic areas. Bioconjugates are prepared by the covalent linkage of active compounds (small or large molecule) to a carrier molecule (lipids, proteins, peptides, carbohydrates, and polymers) through a chemical linker. The linkage of the active component to a carrier molecule enhances the therapeutic window through a targeted delivery and by reducing toxicity. Bioconjugates also possess improved pharmacokinetic properties such as a long half-life, increased stability, and cleavage by intracellular enzymes/environment. However, premature cleavage of the bioconjugates and the resulting metabolites/catabolites may produce undesirable toxic effects and, hence, it is critical to understand cleavage mechanisms, metabolism of bioconjugates, and translatability to human in the discovery stages. This article provides a comprehensive overview of linker cleavage pathways and catabolism/metabolism of antibody–drug conjugates, glycoconjugates, polymer–drug conjugates, lipid–drug conjugates, folate-targeted small molecule–drug conjugates, and drug–drug conjugates.
REPRODUCTIVE ASPECTS IN BRAZILIAN CELIAC WOMEN.

BACKGROUND Celiac disease (CD) is a chronic enteropathy in response to ingestion of gluten. CD was associated with gynecological disorders. OBJECTIVE In this retrospective study, we aimed to investigate the age of menarche, age of menopause, number of pregnancies and abortions in Brazilian celiac patients. METHODS We studied 214 women diagnosed with CD and as control group 286 women were investigated. RESULTS Regarding the mean age of menarche, a significant difference was found (12.6±1.40 in CD and 12.8±1.22 years in healthy group; P=0.04). Regarding abortions, in CD women 38/214 (17.8%) and 28/286 (9.8%) in the control group reported abortion (P=0.0092, OR:1.98; CI95%=1.1- 3.3). There was no significant difference in the mean age of menopause nor number of pregnancies per woman. CONCLUSION In this study, we found that celiac women had a higher mean age of menarche and higher risk of spontaneous abortions.
Adaptation of Mitochondrial Substrate Flux in a Mouse Model of Nonalcoholic Fatty Liver Disease

Maladaptation of mitochondrial oxidative flux seems to be a considerable feature of nonalcoholic fatty liver disease (NAFLD). The aim of this work was to induce NAFLD in mice fed a Western-style diet (WD) and to evaluate liver mitochondrial functions. Experiments were performed on male C57BL/6J mice fed with a control diet or a WD for 24 weeks. Histological changes in liver and adipose tissue as well as hepatic expression of fibrotic and inflammatory genes and proteins were evaluated. The mitochondrial respiration was assessed by high-resolution respirometry. Oxidative stress was evaluated by measuring lipoperoxidation, glutathione, and reactive oxygen species level. Feeding mice a WD induced adipose tissue inflammation and massive liver steatosis accompanied by mild inflammation and fibrosis. We found decreased succinate-activated mitochondrial respiration and decreased succinate dehydrogenase (SDH) activity in the mice fed a WD. The oxidative flux with other substrates was not affected. We observed increased ketogenic capacity, but no impact on the capacity for fatty acid oxidation. We did not confirm the presence of oxidative stress. Mitochondria in this stage of the disease are adapted to increased substrate flux. However, inhibition of SDH can lead to the accumulation of succinate, an important signaling molecule associated with inflammation, fibrosis, and carcinogenesis.
Regulation of Oligodendrocyte Functions: Targeting Lipid Metabolism and Extracellular Matrix for Myelin Repair

Myelin is an essential structure that protects axons, provides metabolic support to neurons and allows fast nerve transmission. Several neurological diseases, such as multiple sclerosis, are characterized by myelin damage, which is responsible of severe functional impairment. Myelin repair requires the timely recruitment of adult oligodendrocyte precursor cells (OPCs) at the lesion sites, their differentiation and maturation into myelinating oligodendrocytes. As a consequence, OPCs undergo profound changes in their morphology, functions, and interactions with other cells and extracellular environment, thus requiring the reorganization of both their lipid metabolism and their membrane composition, which is substantially different compared to other plasma membranes. Despite the growing knowledge in oligodendroglia biology and in the mechanisms involved in OPC-mediated regeneration, the identification of strategies to promote remyelination still remains a challenge. Here, we describe how altered lipid metabolism in oligodendrocytes influences the pathogenesis of demyelination, and we show that several FDA-approved drugs with a previously unknown remyelination potential do act on cholesterol and lipid biosynthetic pathways. Since the interplay between myelin lipids and axons is strictly coordinated by the extracellular matrix (ECM), we also discuss the role of different ECM components, and report the last findings on new ECM-modifiers able to foster endogenous remyelination.
Does the beginning and the end of income poverty affect psychosocial factors among middle-aged and older adults? Findings based on nationally representative longitudinal data

Abstract Objectives: The objective of this study was to determine whether the onset and the end of income poverty were associated with psychosocial factors (depressive symptoms, optimism, loneliness, social isolation, and subjective well-being). Method: For this study, nationally representative longitudinal data were drawn from the German Ageing Survey (wave 5 and wave 6 with n = 8534 in the analytical sample), covering community-dwelling individuals 40 years and over. Widely used and well-established measures were used to quantify psychosocial factors. Asymmetric linear fixed effects (FE) regressions were used. Results: Conventional linear FE regressions showed that changes in income poverty were associated with changes in life satisfaction (β = –0.11, p < .05), changes in positive affect (β = –0.06, p < 0.05), changes in social isolation (β = 0.10, p < 0.05) and changes in optimism (β = –0.06, p < 0.05). Asymmetric linear FE regressions showed that the beginning of income poverty was associated with increases in social isolation (β = 0.14, p < 0.05) and decreases in optimism (β = –0.08, p < 0.05), whereas the end of income poverty was associated with increases in life satisfaction (β = 0.11, p < 0.05). Conclusion: Findings indicate that the onset and the end of income poverty can affect psychosocial factors. More broadly, our findings suggest that upcoming studies should disentangle the consequences of income poverty (distinguishing between the start and the end of income poverty). This has important practical consequences. When individuals fall into poverty, strategies to avoid social isolation and the loss of optimism seems to be important. Furthermore, approaches to leave income poverty may help to rise life satisfaction.
Transverse Right Ventricle Strain and Strain Rate Assessed by 2-Dimensional Speckle Tracking Echocardiography in Dogs with Pulmonary Hypertension

Right ventricular (RV) strain analysis using 2-dimensional speckle tracking echocardiography (2D STE) permits practitioners to assess regional and global deformation of the myocardium. Recently, assessment of the longitudinal right ventricle (RV) strain and strain rate using 2D STE has been reported in dogs. Although longitudinal deformation is the dominant component of the RV systole, RV myocardial fibers of the superficial layer are oriented circumferentially and these contribute to the RV pump function (radial deformation). Because this strain component has not been investigated in dogs, we have assessed radial RV strain and strain rate using 2D STE in healthy dogs and dogs with pulmonary hypertension (PH). We have recruited 74 dogs (40 healthy dogs and 34 dogs with PH) in which we have analyzed radial RV free wall strain and strain rate using XstrainTM software. We have used the left apical 4-chamber view optimized for the RV for analysis of the radial strain and strain rate variables (XstrainTM software denoted radial strain as “transverse”). Seven dogs were excluded during the analysis for low quality images. Transverse strain and strain rate obtained in healthy dogs showed no relationship with heart rate, body weight or age (r2 < 0.09 and p > 0.05 for all variables). Moreover, no relationship between transverse strain/strain rate variables and left atrial-to-aortic ratios was observed (r2 < 0.06 and p = 0.2, for both). Transverse strain and strain rate obtained in dogs with PH, showed weak negative relationships with tricuspid regurgitation velocity (r2 < 0.25 and p = 0.006, for both). Transverse RV strain and strain rate using 2D STE is feasible in most dogs and decrease with worsening of the PH, but these advanced echocardiographic indices do not help in identifying dogs with PH.
Domain-general cognitive functions fully explained growth in nonsymbolic magnitude representation but not in symbolic representation in elementary school children

In this study, we aimed to compare developmental changes in nonsymbolic and symbolic magnitude representations across the elementary school years. For this aim, we used a four-wave longitudinal study with a one-year interval in schoolchildren in grades 1–4 in Russia and Kyrgyzstan (N = 490, mean age was 7.65 years at grade 1). The results of mixed-effects growth models revealed that growth in the precision of symbolic representation was larger than in the nonsymbolic representation. Moreover, growth in nonsymbolic representation was fully explained by growth in fluid intelligence (FI), visuospatial working memory (VSWM) and processing speed (PS). The analysis demonstrated that growth in nonsymbolic magnitude representation was significant only for pupils with a high level of FI and PS, whereas growth in precision of symbolic representation did not significantly vary across pupils with different levels of FI or VSWM.
Enhanced Cypermethrin Degradation Kinetics and Metabolic Pathway in Bacillus thuringiensis Strain SG4

Cypermethrin is popularly used as an insecticide in households and agricultural fields, resulting in serious environmental contamination. Rapid and effective techniques that minimize or remove insecticidal residues from the environment are urgently required. However, the currently available cypermethrin-degrading bacterial strains are suboptimal. We aimed to characterize the kinetics and metabolic pathway of highly efficient cypermethrin-degrading Bacillus thuringiensis strain SG4. Strain SG4 effectively degraded cypermethrin under different conditions. The maximum degradation was observed at 32 °C, pH 7.0, and a shaking speed of 110 rpm, and about 80% of the initial dose of cypermethrin (50 mg·L−1) was degraded in minimal salt medium within 15 days. SG4 cells immobilized with sodium alginate provided a higher degradation rate (85.0%) and lower half-life (t1/2) of 5.3 days compared to the 52.9 days of the control. Bioaugmentation of cypermethrin-contaminated soil slurry with strain SG4 significantly enhanced its biodegradation (83.3%). Analysis of the degradation products led to identification of nine metabolites of cypermethrin, which revealed that cypermethrin could be degraded first by cleavage of its ester bond, followed by degradation of the benzene ring, and subsequent metabolism. A new degradation pathway for cypermethrin was proposed based on analysis of the metabolites. We investigated the active role of B. thuringiensis strain SG4 in cypermethrin degradation under various conditions that could be applied in large-scale pollutant treatment.
Donepezil plus memantine versus donepezil alone for treatment of concomitant Alzheimer’s disease and chronic obstructive pulmonary disease: a retrospective observational study

Objective To assess the clinical outcomes of donepezil plus memantine (DM) and donepezil (DO) alone in Asian patients with a concomitant diagnosis of moderate-to-severe Alzheimer’s disease and mild-to-moderate chronic obstructive pulmonary disease (AD-COPD). Methods We conducted a retrospective analysis of patients with AD-COPD who received either DM or DO for 6 months, or until the occurrence of unacceptable adverse events or disease progression, between June 2012 and May 2016. The primary endpoint was the score on the Standardized Mini-Mental State Examination (SMMSE). Secondary endpoints were scores on the caregiver-rated Bristol Activities of Daily Living Scale, Neuropsychiatric Inventory, Dementia Quality of Life (DEMQOL)-Proxy, and General Health Questionnaire 12. Results In total, 154 eligible patients received DM, whereas 156 received DO. Compared with patients who received DO, patients who received DM had significantly higher mean scores on the SMMSE by 2.1 points (95% confidence interval, 1.3–2.5). Significant between-group heterogeneity was not detected in outcomes over time. The benefits of treatment with DM were greater than those of treatment with DO, in terms of the primary endpoint. Significant differences were also detected in terms of secondary endpoints. Conclusion DM is more effective than DO alone for Asian patients with AD-COPD.
PARP Inhibitors as Therapeutics: Beyond Modulation of PARylation

Poly (ADP-ribose) polymerase (PARP) 1 is an essential molecule in DNA damage response by sensing DNA damage and docking DNA repair proteins on the damaged DNA site through a type of posttranslational modification, poly (ADP-Ribosyl)ation (PARylation). PARP inhibitors, which inhibit PARylation through competitively binding to NAD+ binding site of PARP1 and PARP2, have improved clinical benefits for BRCA mutated tumors, leading to their accelerated clinical application. However, the antitumor activities of PARP inhibitors in clinical development are different, due to PARP trapping activity beyond blocking PARylation reactions. In this review, we comprehensively address the current state of knowledge regarding the mechanisms of action of PARP inhibitors. We will also discuss the different effects of PARP inhibitors in combination with cytotoxic chemotherapeutic agents regarding the mechanism of regulating PARylation.
Catalyst and Instrument of National Growth: Interrogating the Significance of Entrepreneurship in Nigerian Economic Development

Entrepreneurship as it is widely believed is a fueling developmental hub and cause of financial progression of any given economy. The general Entrepreneurial activities have been found to be proficient of creating optimistic and progressive impacts towards nation's economy and improved class of life expectancy of the people. This study based on this, sourced to look at the entrepreneurship as a catalyst and instrument of progress and improvement in Nigeria economy. The study make used of the secondary data and the outcome signposts that entrepreneurship has immensely contributed significantly to the employment generation and growth of Nigerian economy. Some of the major observation is that entrepreneurship development has massively enhanced job creation. And, however consequently lead to economic development. It is recommended that Nigerian should advance more especially some other economic opportunities while government should ensure the enabling environments for purposeful development of entrepreneurship practices. Keywords: Entrepreneurship Development, Impact, Nigeria Economy. DOI : 10.7176/EJBM/12-3-13 Publication date: January 31 st 2020
Stefan Thim, 2012. Phrasal Verbs: The English Verb-Particle Construction and its History (Topics in English Linguistics 78). Berlin and New York: Mouton de Gruyter. Pp. xiv + 302. ISBN 978-3-11- 025702-1

HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L’archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d’enseignement et de recherche français ou étrangers, des laboratoires publics ou privés. Stefan Thim, 2012. Phrasal Verbs: The English Verb-Particle Construction and its History (Topics in English Linguistics 78). Berlin and New York: Mouton de Gruyter. Pp. xiv + 302. ISBN 978-3-11025702-1. Bert Cappelle
A Multiple-Beam Spherical Reflector Antenna

A spherical reflector with multiple feeds is an attractive possibility for application in future communications satellite systems. Data are presented which show that spherical reflectors possessing relatively high gain (40 dB) and very small phase path error (Cx/32) are feasible. A design of a spherical reflector utilizing corrugated horn feeds is considered. Radiation patterns are computed using the physical-optics technique. The designed antenna is approximately 60X in diameter. Calculations performed for this antenna with three beams indicate that each beam has a gain of about 42 dB, a beamwidth of 1.4 deg, and sidelobes that can be expected to be at least 28 dB down. These results indicate that the feature of low sidelobes makes the spherical reflector a promising candidate for a multiple-beam communications satellite antenna.