Miracle-dz/UniFAR-FTUs huggingface dataset:
Future Risks in Patients With Severe Asthma

A major burden of severe asthma is the future risk of adverse health outcomes. Patients with severe asthma are prone to serious exacerbation and deterioration of lung function and may experience side effects of medications such as oral corticosteroids (OCSs). However, such future risk is not easily measurable in daily clinical practice. In particular, currently available tools to measure asthma control and asthma-related quality of life incompletely predict the future risk of medication-related morbidity. This is a significant issue in asthma management. This review summarizes the current evidence of future risk in patients with severe asthma. As future risk is poorly perceived by controlled asthmatics, our review focuses on the risk in patients with ‘controlled’ severe asthma. Of note, it is likely that long-term OCS therapy may not prevent future asthma progression, including lung function decline. In addition, the risk of drug side effects increases even during low-dose OCS therapy. Thus, novel treatments are highly desirable for reducing future risks without any loss of asthma control.
On Scalable Deep Learning and Parallelizing Gradient Descent

Speeding up gradient based methods has been a subject of interest over the past years with many practical applications, especially with respect to Deep Learning. Despite the fact that many optimizations have been done on a hardware level, the convergence rate of very large models remains problematic. Therefore, data parallel methods next to mini-batch parallelism have been suggested [4, 6, 5, 16, 12, 8, 18] to further decrease the training time of parameterized models using gradient based methods. Nevertheless, asynchronous optimization was considered too unstable for practical purposes due to a lacking understanding of the underlying mechanisms. Recently, a theoretical contribution has been made [14] which defines asynchronous optimization in terms of (implicit) momentum due to the presence of a queuing model of gradients based on past parameterizations. This thesis mainly builds upon this work, and [18] to construct a better understanding why asynchronous optimization shows proportionally more divergent behavior when the number of parallel workers increases, and how this affects existing distributed optimization algorithms. Furthermore, using our redefinition of parameter staleness, we construct two novel techniques for asynchronous optimization, i.e., agn and adag. This work shows that these methods outperform existing methods, and are more robust to (distributed) hyperparameterization contrary to existing distributed optimization algorithms such as downpour [4], (a)easgd [18], and dynsgd [8]. Additionally, this thesis presents several smaller contributions. First, we show that the convergence rate of easgd derived algorithms is impaired by an equilibrium condition. However, this equilibrium condition makes sure that easgd does not overfit quickly. Finally, we introduce a new metric, temporal efficiency, to evaluate distributed optimization algorithms against each other.
Tuberculosis in South and Central Africa: Understanding epidemiology - Improving diagnosis and management

Tuberculosis (TB) is a globally leading infectious disease accounting for a particularly high burden of morbidity and mortality in sub-Saharan Africa. Knowledge of local TB epidemiology is a prerequisite for improving effective TB management but is often limited in settings with scarce resources and for vulnerable populations. Studying epidemiologic aspects of TB in Gabon we revealed a high rate of TB/HIV co-infection (42% in adults and 16% in children), limited access to first-line and second-line TB drugs entailing incorrect or unavailable TB treatment regimens, a low treatment success rate (53%) with a high mortality rate in TB/HIV co-infected patients (25%), and drug-resistant TB as major public health concern (31% multi-drug resistant TB in re-treatment TB cases). In South African children with suspected pulmonary TB (PTB) we found that focused point-of-care ultrasound for extra-pulmonary TB (EPTB) was a feasible diagnostic imaging tool that revealed a high prevalence of sonographic findings suggestive of concurrent EPTB in children with confirmed and unconfirmed PTB (31% and 30% versus 15% in children with unlikely TB) and contributed to effective monitoring of TB treatment response. We further found that in children administration of TB drugs differed substantially from recommended practice, potentially contributing to sub-therapeutic drug levels. In summary, the results presented in this thesis identified starting points for improving management of TB in Gabon and showed that point-of-care ultrasound can contribute to timely diagnosis of childhood TB and to monitoring TB treatment response.
Cigarette Smoke Reduces Fatty Acid Catabolism, Leading to Apoptosis in Lung Endothelial Cells: Implication for Pathogenesis of COPD

Endothelial cell (EC) apoptosis contributes to cigarette smoke (CS)-induced pulmonary emphysema. Metabolism of glucose, glutamine, and fatty acid is dysregulated in patients with chronic obstructive pulmonary disease (COPD). Whether CS causes metabolic dysregulation in ECs leading to development of COPD remains elusive. We hypothesized that CS alters metabolism, resulting in apoptosis in lung ECs. To test this hypothesis, we treated primary mouse pulmonary microvascular ECs (PMVECs) with CS extract (CSE) and employed PMVECs from healthy subjects and COPD patients. We found that mitochondrial respiration was reduced in CSE-treated PMVECs and in PMVECs from COPD patients. Specifically, oxidation of fatty acids (FAO) was reduced in these cells, which linked to reduced carnitine palmitoyltransferase 1a (Cpt1a), an essential enzyme for carnitine shuttle. CSE-induced apoptosis was further increased when cells were treated with a specific Cpt1 inhibitor etomoxir or transfected with Cpt1a siRNA. L-Carnitine treatment augmented FAO but attenuated CSE-induced apoptosis by upregulating Cpt1a. CSE treatment increased palmitate-derived ceramide synthesis, which was reduced by L-carnitine. Although CSE treatment increased glycolysis, inhibiting glycolysis with 2-deoxy-d-glucose had no effects on CSE-mediated apoptosis in lung ECs. Conclusively, FAO reduction increases ceramide and apoptosis in lung ECs treated with CSE, which may contribute to the pathogenesis of COPD/emphysema.
The Role of Mindfulness in Predicting Pain Interference in Patients with Primary Headache

Background Primary headaches are one of the most troubled chronic diseases. Headaches interfere within the various dimensions of the patient’s life. Coping strategies that aim to be attention focused (e.g., mindfulness) may moderate pain-related emotional and physical interference. Objectives This investigation examined the relationship between mindfulness and pain intensity with physical and emotional interference and the subsequent aim was to analyze the role of mindfulness and headache severity combination in the prediction of pain-related interference. Methods This correlational study was conducted during years 2017 to 2018 at Imam Hossein Hospital of Tehran province. Eighty-five patients (56 females and 29 males), who had one type of primary headache were selected through purposive sampling after the diagnosis by a neurologist. The data were collected through the brief pain inventory (BPI) and the mindful attention awareness scale (MAAS). All data were analyzed using descriptive statistics. Bivariate correlation matrix and hierarchical stepwise linear regression statistics were used. Results The correlational analysis of the results indicated significant association between mindfulness (MAAS) and pain severity (BPI) (P < 0.01) as well as the findings of the study point to the significant relationship between mindfulness and both physical and emotional pain-related interference (P < 0.01). The results of stepwise linear regression indicated that pain severity explains only 1% of the total score in emotional pain-related interference (P = 0.003 and ΔF (1 and 83) = 9.22, ΔR2 = 0.11). Adding mindfulness to the model led to a 43% increase of the explained variance (R2 Change = 0.34). In physical interference, although pain severity was able to predict pain interference (P = 0.01 and ΔF (1 and 83) = 7.09, ΔR2 = 0.07), a combination model justifies 10% of the interference variance that was not statistically meaningful (P = 0.08, ΔR2 = 0.103). Conclusions This result is a further support that Mindful Awareness contributed to emotional pain-related interference prediction. This result can explain the role of attention focused and mindful awareness in primary headache pain adjustment.
Pregnant and non-pregnant women and low back pain-related differences on postural control measures during different balance tasks

Introduction: Low back pain (LBP) is the most common musculoskeletal complaint in pregnancy, being responsible for many negative impacts. Objective: To evaluate the effect of LBP on static and dynamic balance in pregnant women and whether pregnancy mediates the results compared to non-pregnant women. Methods: 44 women (mean age 30 yrs) participated voluntarily in this study: 16 pregnant women with LBP starting in pregnancy, 14 pregnant women without LBP and 14 non-pregnant women as a group control. Participants were assessed for static postural balance using a force platform and dynamic mobility balance using the Timed Up and Go (TUG) test. Results: The pregnant women with LBP showed significant (P < 0.04, for mean, d= 1,2) poor postural balance in static tests (force platform), in the area of COP eyes open. In dynamic balance (TUG test), statistical difference was found between the groups (P 0.038) and the effect size were moderate to strong in the comparison between the three groups. The most sensitive differences were reported mainly between pregnant women with LBP versus non-pregnant control group in balance measures from force platform. Conclusion: The findings indicate that LBP associated to pregnant clinical status can decrease the balance capacity in women. These results have implication for balance evaluation and retraining in pregnant women with and without LBP from rehabilitation or prevention programs.
Relationship Between Corrective Saccades and Measures of Physical Function in Unilateral and Bilateral Vestibular Loss.

OBJECTIVES Following the loss of vestibular function, some patients functionally improve and are minimally bothered by their loss of peripheral function while others remain more symptomatic and are unable to return to their activities of daily living. To date, the mechanisms for functional improvement remain poorly understood. The purpose of the present study was to examine the association between corrective saccades and measures of handicap, dynamic visual acuity, gait, and falls. DESIGN A retrospective chart review was performed to identify patients who were diagnosed with unilateral or bilateral vestibular hypofunction and who also completed a baseline vestibular rehabilitation evaluation. A total of 82 patients with unilateral vestibular hypofunction and 17 patients with bilateral vestibular hypofunction were identified. The video head impulse test results for each patient were grouped based on the type of presenting saccades. Specifically, the saccade grouping included the following: (1) covert, (2) overt, or (3) a combination of both types of saccades. RESULTS The results show that covert saccades are associated with better performance on measures of dynamic visual acuity, gait, and balance in patients with unilateral vestibular hypofunction. Patients exhibiting overt saccades or combination of both covert and overt saccades were more often found to have an abnormal gait speed and be characterized as being at risk for falls using the Dynamic Gait Index. We observed no differences in physical function for those patients with bilateral vestibular hypofunction as a function of saccade grouping. CONCLUSIONS When comparing saccade groups (covert, overt, or combination of both), patients with unilateral vestibular hypofunction and covert saccades demonstrated better performance on standard baseline physical therapy measures of dynamic visual acuity and gait and balance. We did not observe any significant associations between saccade group and physical function in patients with bilateral vestibular hypofunction; however, additional studies are needed with adequate sample sizes. Our findings may suggest that corrective saccade latency in patients with unilateral vestibular hypofunction is related to measures of physical function. The extent to which saccade latency has the potential to be a useful target for vestibular rehabilitation is still to be determined and may be promising target to improve functional outcomes.
Determinants of change in arterial stiffness over 5 years in early chronic kidney disease.

BACKGROUND Arterial stiffness (AS) is an established and potentially modifiable risk factor for cardiovascular disease associated with chronic kidney disease (CKD). There have been few studies to evaluate the progression of AS over time or factors that contribute to this, particularly in early CKD. We therefore investigated AS over 5 years in an elderly population with CKD Stage 3 cared for in primary care. METHODS A total of 1741 persons with an estimated glomerular filtration rate of 30-59 mL/min/1.73 m2 underwent detailed clinical and biochemical assessment at baseline and Years 1 and 5. Carotid to femoral pulse wave velocity (PWV) was measured to assess AS using a Vicorder device. RESULTS 970 participants had PWV assessments at baseline and 5 years. PWV increased significantly by a mean of 1.1 m/s (from 9.7 ± 1.9 to 10.8 ± 2.1 m/s). Multivariable linear regression analysis identified the following independent determinants of ΔPWV at Year 5: baseline age, diabetes status, baseline systolic blood pressure (SBP) and diastolic blood pressure, baseline PWV, ΔPWV at 1 year, ΔSBP over 5 years and Δserum bicarbonate over 5 years (R2 = 0.38 for the equation). CONCLUSIONS We observed a clinically significant increase in PWV over 5 years in a cohort with early CKD despite reasonably well-controlled hypertension. Measures of BP were identified as the most important modifiable determinant of ΔPWV, suggesting that interventions to prevent arterial disease should focus on improved control of BP, particularly in those who evidence an early increase in PWV. These hypotheses should now be tested in prospective trials.
Trial watch: dendritic cell vaccination for cancer immunotherapy

ABSTRACT Dendritic- cells (DCs) have received considerable attention as potential targets for the development of anticancer vaccines. DC-based anticancer vaccination relies on patient-derived DCs pulsed with a source of tumor-associated antigens (TAAs) in the context of standardized maturation-cocktails, followed by their reinfusion. Extensive evidence has confirmed that DC-based vaccines can generate TAA-specific, cytotoxic T cells. Nonetheless, clinical efficacy of DC-based vaccines remains suboptimal, reflecting the widespread immunosuppression within tumors. Thus, clinical interest is being refocused on DC-based vaccines as combinatorial partners for T cell-targeting immunotherapies. Here, we summarize the most recent preclinical/clinical development of anticancer DC vaccination and discuss future perspectives for DC-based vaccines in immuno-oncology.
Effects and mechanism of siomycin A on the growth and apoptosis of MiaPaCa-2 cancer cells

Siomycin A is a type of thiopeptide antibiotic that is isolated from the fermentation products of an endophytic actinomycin, which is derived from the medicinal plant Acanthopanax senticosus. The present study investigated whether siomycin A has antitumor effects in vitro on a variety of cell lines. A Cell Counting Kit-8 assay was performed to detect the effects of siomycin A on cell viability; morphological changes in the MiaPaCa-2 cell line were analyzed using an inverted phase contrast microscope. A Transwell migration assay was applied to detect cell migration ability. The cytoskeleton was observed by laser confocal microscopy, and apoptosis was detected using flow cytometry. A western blot assay was used to detect the expression of matrix metalloproteinase (MMP)-2, MMP-9 and α-tubulin. The results revealed that siomycin A inhibited the proliferation of human tumor cell lines of different origins. As the concentration of siomycin A increased, the cell density decreased gradually and cells exhibited a morphological change from spindle to spherical shape. Furthermore, 24 h after administration, the cell migration ability was inhibited. The cytoskeleton complexity and morphological changes were increased after administration of siomycin A. The percentage of apoptotic cells was significantly increased and the expression levels of MMP-2, MMP-9 and α-tubulin were downregulated by siomycin A. Therefore, siomycin A was determined to effectively inhibit the proliferative ability of a variety of human tumor cell lines. Siomycin A was also determined to affect the cytoskeleton of tumor cells by downregulating the expression of α-tubulin protein.
Serum uric acid level in type 2 diabetes mellitus

Background: Diabetes mellitus is the most important risk factor associated with two to four fold increased incidence of coronary artery disease. The major risk factors for CAD are hypercholesterolemia, hypertension, diabetes mellitus, and cigarette smoking Objectives: To study the level of serum uric acid in type 2 diabetes mellitus and the correlation between elevated serum uric acid level and the component of metabolic syndrome like obesity, hypertension, dyslipidemia.Methods: The study was done as descriptive analytical study among the diabetic patients in a tertiary care setting during the period January 2018 to February 2019. The inclusion and exclusion criteria were clearly defined and the study participants were recruited for the study after getting the informed consent. The socio demographic profile, clinical and laboratory data were collected from the blood sample obtained from the patients with the standardized procedures. Data was entered in Microsoft excel spread sheet and analyzed statistically using SPSS statistical software. Student ‘t’ test and Chi-square test values were applied for significance.Results: Serum uric acid in the study population and control varied from 3.0 to 8.1 and 2.7 to 5.5 mg/dl respectively. The mean and standard deviation of uric acid among cases was 5.08±1.42 while in control it was 3.55±0.62 respectively. The serum uric acid level of diabetics was very much elevated compare with controls and it was highly significant. Significant correlation was noticed between serum uric acid and BMI as well as WHR. Elevated uric acid levels were significantly noticed among those with hypertension, dyslipidemia, coronary artery disease and chronicity of the diabetes.Conclusions: Uric acid was significantly elevated in diabetic population and the mean value of serum uric acid level was higher in longer duration of diabetes, hypertension, dyslipidemia, central obesity which are the components of metabolic syndrome.
Doing Case Study Research: A Practical Guide for Beginning Researchers. Third Edition.

This step-by-step handbook guides beginning researchers through the stages of planning and implementing case studies. Starting with how to establish a rationale for conducting a systematic case study and identifying literature that informs the research effort, this indispensable resource shows students how to determine an appropriate research design and conduct informative interviews, observations and document analyses. It also describes how to derive meaning from data and how to communicate results. Finally, the authors delineate the ways to verify the results attained. Students and advisors can use these easy-to-follow steps to shape a thesis, dissertation, or independent project from conceptualization to completion. This book features: a step-by-step approach that speaks directly to the novice investigator; many concrete examples to illustrate key concepts; and questions, illustrations, and activities to reinforce what has been learned.
Upper Airway Changes following Functional Treatment with the Headgear Herbst or Headgear Twin Block Appliance Assessed on Lateral Cephalograms and Magnetic Resonance Imaging

Objective The present study compared the changes in the upper airway dimensions and sleep-related breathing disorder (SRBD) condition between functional treatment with the headgear Herbst (HG-Herbst) and headgear Twin Block (HG-TB) appliance. Soft tissues were assessed on lateral cephalometric X-ray and magnetic resonance imaging (MRI). Materials and Methods Consecutive patients who sought orthodontic treatment at the Faculty of Dentistry of The University of Hong Kong were screened. Adolescents (12-17 year sold for boys and 10-15 years old for girls), with class II molar relationship and overjet >5 mm, with no severe transverse maxillary deficiency, were recruited. Patients were assigned either to the HG-Herbst or to the HG-TB treatment by stratified block randomisation, with sex as the stratification factor. Lateral cephalograms, magnetic resonance imaging (MRI), and the Paediatric Sleep Questionnaire (PSQ) were obtained at baseline and after treatment. Results 28 patients were enrolled, and 26 patients (13 in each group) completed the treatment. Following 1 year of functional appliance treatment, a significantly lower increase of the lower anterior facial height was observed in the HG-Herbst group compared to the HG-TB group (p = 0.024). However, no significant differences were observed in the upper airway structures or SRBD between the two groups. Conclusion The changes in upper airway dimensions and SRBD condition were not significantly different between the HG-Herbst and the HG-TB appliance treatment. Additional studies with larger sample size are warranted.
Development and Preliminary Validation of a Stroke Physical Activity Questionnaire

Objective The aim of the current study was to develop and then to determine preliminary validity of a physical activity questionnaire specifically designed for ambulatory, chronic stroke patients. Methods This cross-sectional study recruited 92 chronic stroke patients. In Phase I, the SPAQ was developed and its content validity index (CVI) determined. In Phase II, we examined (1) the concurrent validity of SPAQ vs. the International Physical Activity Questionnaire-Short Form (IPAQ-SF); (2) the convergent validity of SPAQ vs. the Functional Ambulation Category (FAC), vs. the six-minute walk test (6-MWT), vs. the timed up and go test (TUGT), vs. the Motricity Index, vs. the National Institutes of Health Stroke Scale (NIHSS), and vs. the Modified Rankin Scale (MRS); and (3) the discriminant validity of the SPAQ vs. the Montreal Cognitive Assessment (MoCA). The concurrent validity and convergent and divergent validity were analysed using Spearman's rank correlation coefficient. The agreement between the SPAQ and IPAQ-SF was assessed using the Kappa statistic. Results The SPAQ has 12 items in 3 main components which covers low (7 items), moderate (3 items), and vigorous (2 items) physical activity. The SPAQ had a CVI of 0.93. Spearman's correlation coefficient (rs) for SPAQ vs. IPAQ-SF was 0.53 (p < 0.001). The SPAQ yielded substantial agreement with the IPAQ-SF (Kappa = 0.65). For convergent validity, the SPAQ had a moderate correlation with the 6-MWT, MI, NIHSS, FAC, TUGT, and MRS (p < 0.05). For discriminant validity, the SPAQ was not correlated with the MoCA (rs = 0.061, p = 0.68). Conclusion The SPAQ can be used to practically assess physical activity in chronic stroke patients, and it has acceptable psychometric properties which are comparable to other standard physical activity questionnaires. Future work should determine the validity of the SPAQ using an objective device such as an accelerometer.