bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Bayesian and frequentist group-sequential clinical trial designs
Authors: Stallard Nigel , Todd Susan , Ryan Elizabeth G. , Gates Simon
Published: January 2020

Background

There is a growing interest in the use of Bayesian adaptive designs in late-phase clinical trials. This includes the use of stopping rules based on Bayesian analyses in which the frequentist type I error rate is controlled as in frequentist group-sequential designs.

Methods

This paper presents a practical comparison of Bayesian and frequentist group-sequential tests. Focussing on the setting in which data can be summarised by normally distributed test statistics, we evaluate and compare boundary values and operating characteristics.

Results

Although Bayesian and frequentist group-sequential approaches are based on fundamentally different paradigms, in a single arm trial or two-arm comparative trial with a prior distribution specified for the treatment difference, Bayesian and frequentist group-sequential tests can have identical stopping rules if particular critical values with which the posterior probability is compared or particular spending function values are chosen. If the Bayesian critical values at different looks are restricted to be equal, O’Brien and Fleming’s design corresponds to a Bayesian design with an exceptionally informative negative prior, Pocock’s design to a Bayesian design with a non-informative prior and frequentist designs with a linear alpha spending function are very similar to Bayesian designs with slightly informative priors.This contrasts with the setting of a comparative trial with independent prior distributions specified for treatment effects in different groups. In this case Bayesian and frequentist group-sequential tests cannot have the same stopping rule as the Bayesian stopping rule depends on the observed means in the two groups and not just on their difference. In this setting the Bayesian test can only be guaranteed to control the type I error for a specified range of values of the control group treatment effect.

Conclusions

Comparison of frequentist and Bayesian designs can encourage careful thought about design parameters and help to ensure appropriate design choices are made.
Value of pyrazinamide for composition of new treatment regimens for multidrug-resistant Mycobacterium tuberculosis in China
Authors: Xia Hui , van den Hof Susan , Cobelens Frank , Zhou Yang , Zhao Bing , Wang Shengfen , Zhao Yanlin
Published: January 2020

Background

Pyrazinamide still may be a useful drug for treatment of rifampin-resistant (RR-TB) or multidrug-resistant tuberculosis (MDR-TB) in China while awaiting scale up of new drugs and regimens including bedaquiline and linezolid. The level of pyrazinamide resistance among MDR-TB patients in China is not well established. Therefore, we assessed pyrazinamide resistance in a representative sample and explored determinants and patterns of pncA mutations.

Methods

MDR-TB isolates from the 2007 national drug resistance survey of China were sub-cultured and examined for pyrazinamide susceptibility by BACTEC MGIT 960 method. pncA mutations were identified by sequencing. Characteristics associated with pyrazinamide resistance were analyzed using univariable and multivariable log-binominal regression.

Results

Of 401 MDR-TB isolates, 324 were successfully sub-cultured and underwent drug susceptibility testing. Pyrazinamide resistance was prevalent in 40.7% of samples, similarly among new and previously treated MDR-TB patients. Pyrazinamide resistance in MDR-TB patients was associated with lower age (adjusted OR 0.54; 95% CI, 0.34–0.87 for those aged ≧60 years compared to < 40 years). Pyrazinamide resistance was not associated with gender, residential area, previous treatment history and Beijing genotype. Of 132 patients with pyrazinamide resistant MDR-TB, 97 (73.5%) had a mutation in the pncA gene; with 61 different point mutations causing amino acid change, and 11 frameshifts in the pncA gene. The mutations were scattered throughout the whole pncA gene and no hot spot region was identified.

Conclusions

Pyrazinamide resistance among MDR-TB patients in China is common, although less so in elderly patients. Therefore, pyrazinamide should only be used for treatment of RR/MDR-TB in China if susceptibility is confirmed. Molecular testing for detection of pyrazinamide resistance only based on pncA mutations has certain value for the rapid detection of pyrazinamide resistance in MDR-TB strains but other gene mutations conferring to pyrazinamide resistance still need to be explored to increase its predictive ability .
Intensity of perinatal care for extremely preterm babies and outcomes at a higher gestational age: evidence from the EPIPAGE-2 cohort study
Authors: Morgan Andrei Scott , Khoshnood Babak , Diguisto Caroline , Foix L’Helias Laurence , Marchand-Martin Laetitia , Kaminski Monique , Zeitlin Jennifer , Bréart Gérard , Goffinet François , Ancel Pierre-Yves
Published: January 2020

Background

Perinatal decision-making affects outcomes for extremely preterm babies (22–26 weeks’ gestational age (GA)): more active units have improved survival without increased morbidity. We hypothesised such units may gain skills and expertise meaning babies at higher gestational ages have better outcomes than if they were born elsewhere. We examined mortality and morbidity outcomes at age two for babies born at 27–28 weeks’ GA in relation to the intensity of perinatal care provided to extremely preterm babies.

Methods

Fetuses from the 2011 French national prospective EPIPAGE-2 cohort, alive at maternal admission to a level 3 hospital and delivered at 27–28 weeks’ GA, were included. Morbidity-free survival (survival without sensorimotor (blindness, deafness or cerebral palsy) disability) and overall survival at age two were examined. Sensorimotor disability and Ages and Stages Questionnaire (ASQ) result below threshold among survivors were secondary outcomes. Perinatal care intensity level was based on birth hospital, grouped using the ratio of 24–25 weeks’ GA babies admitted to neonatal intensive care to fetuses of the same gestation alive at maternal admission. Sensitivity analyses used ratios based upon antenatal steroids, Caesarean section, and newborn resuscitation. Multiple imputation was used for missing data; hierarchical logistic regression accounted for births nested within centres.

Results

633 of 747 fetuses (84.7%) born at 27–28 weeks’ GA survived to age two. There were no differences in survival or morbidity-free survival: respectively, fully adjusted odds ratios were 0.96 (95% CI: 0.54 to 1.71) and 1.09 (95% CI: 0.59 to 2.01) in medium and 1.12 (95% CI: 0.63 to 2.00) and 1.16 (95% CI: 0.62 to 2.16) in high compared to low-intensity hospitals. Among survivors, there were no differences in sensorimotor disability or ASQ below threshold. Sensitivity analyses were consistent with the main results.

Conclusions

No difference was seen in survival or morbidity-free survival at two years of age among fetuses alive at maternal hospital admission born at 27–28 weeks’ GA, or in sensorimotor disability or presence of an ASQ below threshold among survivors. There is no evidence for an impact of intensity of perinatal care for extremely preterm babies on births at a higher gestational age.
Improving the psychometric properties of the dissociative experiences scale (DES-II): a Rasch validation study
Authors: Saggino Aristide , Molinengo Giorgia , Rogier Guyonne , Garofalo Carlo , Loera Barbara , Tommasi Marco , Velotti Patrizia
Published: January 2020

Background

The Dissociative Experiences Scale-II (DES-II) is a self-report questionnaire that measures dissociative experiences such as derealization, depersonalization, absorption and amnesia. The DES-II has been prevalently used as a screening tool in patients suffering from psychotic disorders or schizophrenia. However, dissociative experiences can also be part of normal psychological life. Despite its popularity, the most problematic aspect of the DES-II is the inconsistency in its factor structure, which is probably due to the tendency to treat ordinal responses as responses on an interval scale, as it is assumed in the Classical Test Theory approach. In order to address issues related to the inconsistency of previous results, the aim of the present study was to collect new psychometric evidence to improve the properties of the DES-II using Rasch analysis, i.e. analyzing the functioning of the response scale.

Methods

Data were obtained on a sample composed by 320 Italian participants (122 inmates and 198 community-dwelling individuals) and were analyzed with the Rasch model. This model allows the estimation of participants’ level of dissociation, the degree of misfit of each item, the reliability of each item, and their measurement invariance. Moreover, Rasch estimation allows to determine the best response scale, in terms of response modalities number and their discriminant power.

Results

Three items of the scale had strong misfit. After their deletion, the resulting scale was composed by 25 items, which had low levels of misfit and high reliability, and showed measurement invariance. Participants tended to select more often lower categories of the response scale.

Conclusions

Results provided new knowledge on the DES-II structure and its psychometric properties, contributing to the understanding and measurement of the dissociation construct.
Advocating an attack against severe malaria: a cost-effectiveness analysis
Authors: Greenhalgh Scott , Chandwani Veda
Published: January 2020

Background

A recent study found that the gut microbiota, Lactobacillus and Bifidobacterium, have the ability to modulate the severity of malaria. The modulation of the severity of malaria is not however, the typical focal point of most widespread interventions. Thus, an essential element of information required before serious consideration of any intervention that targets reducing severe malaria incidence is a prediction of the health benefits and costs required to be cost-effective.

Methods

Here, we developed a mathematical model of malaria transmission to evaluate an intervention that targets reducing severe malaria incidence. We consider intervention scenarios of a 2-, 7-, and 14-fold reduction in severe malaria incidence, based on the potential reduction in severe malaria incidence caused by gut microbiota, under entomological inoculation rates occurring in 41 countries in sub-Saharan Africa. For each intervention scenario, disability-adjusted life years averted and incremental cost-effectiveness ratios were estimated using country specific data, including the reported proportions of severe malaria incidence in healthcare settings.

Results

Our results show that an intervention that targets reducing severe malaria incidence with annual costs between $23.65 to $30.26 USD per person and causes a 14-fold reduction in severe malaria incidence would be cost-effective in 15–19 countries and very cost-effective in 9–14 countries respectively. Furthermore, if model predictions are based on the distribution of gut microbiota through a freeze-dried yogurt that cost $0.20 per serving, a 2- to 14-fold reduction in severe malaria incidence would be cost-effective in 29 countries and very cost-effective in 25 countries.

Conclusion

Our findings indicate interventions that target severe malaria can be cost-effective, in conjunction with standard interventions, for reducing the health burden and costs attributed to malaria. While our results illustrate a stronger cost-effectiveness for greater reductions, they consistently show that even a limited reduction in severe malaria provides substantial health benefits, and could be economically viable. Therefore, we suggest that interventions that target severe malaria are worthy of consideration, and merit further empirical and clinical investigation.
Screening of cellulolytic bacteria from rotten wood of Qinling (China) for biomass degradation and cloning of cellulases from Bacillus methylotrophicus
Authors: Ma Lingling , Lu Yingying , Yan Hong , Wang Xin , Yi Yanglei , Shan Yuanyuan , Liu Bianfang , Zhou Yuan , Lü Xin
Published: January 2020

Background

Cellulosic biomass degradation still needs to be paid more attentions as bioenergy is the most likely to replace fossil energy in the future, and more evaluable cellulolytic bacteria isolation will lay a foundation for this filed. Qinling Mountains have unique biodiversity, acting as promising source of cellulose-degrading bacteria exhibiting noteworthy properties. Therefore, the aim of this work was to find potential cellulolytic bacteria and verify the possibility of the cloning of cellulases from the selected powerful bacteria.

Results

In present study, 55 potential cellulolytic bacteria were screened and identified from the rotten wood of Qinling Mountains. Based on the investigation of cellulase activities and degradation effect on different cellulose substrates,Bacillus methylotrophicus1EJ7,Bacillus subtilis1AJ3 andBacillus subtilis3BJ4 were further applied to hydrolyze wheat straw, corn stover and switchgrass, and the results suggested thatB. methylotrophicus1EJ7 was the most preponderant bacterium, and which also indicated thatBacilluswas the main cellulolytic bacteria in rotten wood. Furthermore, scanning electron microscopy (SEM) and X-ray diffraction analysis of micromorphology and crystallinity of wheat straw also verified the significant hydrolyzation. With ascertaining the target sequence of cellulase β-glucosidase (243 aa) and endoglucanase (499 aa) were successfully heterogeneously cloned and expressed fromB. methylotrophicus1EJ7, and which performed a good effect on cellulose degradation with enzyme activity of 1670.15 ± 18.94 U/mL and 0.130 ± 0.002 U/mL, respectively. In addition, based on analysis of amino acid sequence, it found that β-glucosidase were belonged to GH16 family, and endoglucanase was composed of GH5 family catalytic domain and a carbohydrate-binding module of CBM3 family.

Conclusions

Based on the screening, identification and cellulose degradation effect evaluation of cellulolytic bacteria from rotten wood of Qinling Mountains, it found thatBacilluswere the predominant species among the isolated strains, andB. methylotrophicus1EJ7 performed best on cellulose degradation. Meanwhile, the β-glucosidase and endoglucanase were successfully cloned and expressed fromB. methylotrophicusfor the first time, which provided new materials of both strain and the recombinant enzymes for the study of cellulose degradation and its application in industry.
Validation of a competence-based assessment of medical students’ performance in the physician’s role
Authors: Prediger Sarah , Schick Kristina , Fincke Fabian , Fürstenberg Sophie , Oubaid Viktor , Kadmon Martina , Berberat Pascal O. , Harendza Sigrid
Published: January 2020

Background

Assessing competence of advanced undergraduate medical students based on performance in the clinical context is the ultimate, yet challenging goal for medical educators to provide constructive alignment between undergraduate medical training and professional work of physicians. Therefore, we designed and validated a performance-based 360-degree assessment for competences of advanced undergraduate medical students.

Methods

This study was conducted in three steps: 1) Ten facets of competence considered to be most important for beginning residents were determined by a ranking study with 102 internists and 100 surgeons. 2) Based on these facets of competence we developed a 360-degree assessment simulating a first day of residency. Advanced undergraduate medical students (year 5 and 6) participated in the physician’s role. Additionally knowledge was assessed by a multiple-choice test. The assessment was performed twice (t1 and t2) and included three phases: a consultation hour, a patient management phase, and a patient handover. Sixty-seven (t1) and eighty-nine (t2) undergraduate medical students participated. 3) The participants completed the Group Assessment of Performance (GAP)-test for flight school applicants to assess medical students‘ facets of competence in a non-medical context for validation purposes. We aimed to provide a validity argument for our newly designed assessment based on Messick’s six aspects of validation: (1) content validity, (2) substantive/cognitive validity, (3) structural validity, (4) generalizability, (5) external validity, and (6) consequential validity.

Results

Our assessment proved to be well operationalised to enable undergraduate medical students to show their competences in performance on the higher levels of Bloom’s taxonomy. Its generalisability was underscored by its authenticity in respect of workplace reality and its underlying facets of competence relevant for beginning residents. The moderate concordance with facets of competence of the validated GAP-test provides arguments of convergent validity for our assessment. Since five aspects of Messick’s validation approach could be defended, our competence-based 360-degree assessment format shows good arguments for its validity.

Conclusion

According to these validation arguments, our assessment instrument seems to be a good option to assess competence in advanced undergraduate medical students in a summative or formative way. Developments towards assessment of postgraduate medical trainees should be explored.
Identification of biomarkers and drug repurposing candidates based on an immune-, inflammation- and membranous glomerulonephritis-associated triplets network for membranous glomerulonephritis
Authors: Zhang Chengwei , Leng Lei , Li Zhaozheng , Zhao Yao , Jiao Jundong
Published: January 2020

Background

Membranous glomerulonephritis (MGN) is a common kidney disease. Despite many evidences support that many immune and inflammation-related genes could serve as effective biomarkers and treatment targets for MGN patients, the potential associations among MGN-, immune- and inflammation-related genes have not been sufficiently understood.

Methods

Here, a global immune-, inflammation- and MGN-associated triplets (IIMATs) network is constructed and analyzed. An integrated and computational approach is developed to identify dysregulated IIMATs for MGN patients based on expression and interaction data.

Results

45 dysregulated IIMATs are identified in MGN by above method. Dysregulated patterns of these dysregulated IIMATs are complex and various. We identify four core clusters from dysregulated IIMATs network and some of these clusters could distinguish MGN and normal samples. Specially, some anti-cancer drugs including Tamoxifen, Bosutinib, Ponatinib and Nintedanib could become candidate drugs for MGN based on drug repurposing strategy follow IIMATs. Functional analysis shows these dysregulated IIMATs are associated with some key functions and chemokine signaling pathway.

Conclusions

The present study explored the associations among immune, inflammation and MGN. Some effective candidate drugs for MGN were identified based on immune and inflammation. Overall, these comprehensive results provide novel insights into the mechanisms and treatment of MGN.
Sodium-glucose co-transporter 2 inhibition as a mitochondrial therapy for atrial fibrillation in patients with diabetes?
Authors: Yurista Salva R. , Silljé Herman H. W. , Rienstra Michiel , de Boer Rudolf A. , Westenbrink B. Daan
Published: January 2020

While patients with type 2 diabetes mellitus (T2DM) are at increased risk to develop atrial fibrillation (AF), the mechanistic link between T2DM and AF-susceptibility remains unclear. Common co-morbidities of T2DM, particularly hypertension, may drive AF in the setting of T2DM. But direct mechanisms may also explain this relation, at least in part. In this regard, recent evidence suggests that mitochondrial dysfunction drives structural, electrical and contractile remodelling of atrial tissue in patients T2DM. Mitochondrial dysfunction may therefore be the mechanistic link between T2DM and AF and could also serve as a therapeutic target. An elegant series of experiments published in Cardiovascular Diabetology provide compelling new evidence to support this hypothesis. Using a model of high fat diet (HFD) and low-dose streptozotocin (STZ) injection, Shao et al. provide data that demonstrate a direct association between mitochondrial dysfunction and the susceptibility to develop AF. But the authors also demonstrated that the sodium-glucose co-transporter 2 inhibitors (SGLT2i) empagliflozin has the capacity to restore mitochondrial function, ameliorate electrical and structural remodelling and prevent AF. These findings provide a new horizon in which mitochondrial targeted therapies could serve as a new class of antiarrhythmic drugs.
Phosphatidylcholine PC ae C44:6 in cerebrospinal fluid is a sensitive biomarker for bacterial meningitis
Authors: de Araujo Leonardo Silva , Pessler Kevin , Sühs Kurt-Wolfram , Novoselova Natalia , Klawonn Frank , Kuhn Maike , Kaever Volkhard , Müller-Vahl Kirsten , Trebst Corinna , Skripuletz Thomas , Stangel Martin , Pessler Frank
Published: January 2020

Background

The timely diagnosis of bacterial meningitis is of utmost importance due to the need to institute antibiotic treatment as early as possible. Moreover, the differentiation from other causes of meningitis/encephalitis is critical because of differences in management such as the need for antiviral or immunosuppressive treatments. Considering our previously reported association between free membrane phospholipids in cerebrospinal fluid (CSF) and CNS involvement in neuroinfections we evaluated phosphatidylcholine PC ae C44:6, an integral constituent of cell membranes, as diagnostic biomarker for bacterial meningitis.

Methods

We used tandem mass spectrometry to measure concentrations of PC ae C44:6 in cell-free CSF samples (n = 221) from patients with acute bacterial meningitis, neuroborreliosis, viral meningitis/encephalitis (herpes simplex virus, varicella zoster virus, enteroviruses), autoimmune neuroinflammation (anti-NMDA-receptor autoimmune encephalitis, multiple sclerosis), facial nerve and segmental herpes zoster (shingles), and noninflammatory CNS disorders (Bell’s palsy, Tourette syndrome, normal pressure hydrocephalus).

Results

PC ae C44:6 concentrations were significantly higher in bacterial meningitis than in all other diagnostic groups, and were higher in patients with a classic bacterial meningitis pathogen (e.g. Streptococcus pneumoniae, Neisseria meningitidis, Staphylococcus aureus) than in those with less virulent or opportunistic pathogens as causative agents (P = 0.026). PC ae C44:6 concentrations were only moderately associated with CSF cell count (Spearman’s ρ = 0.45; P = 0.009), indicating that they do not merely reflect neuroinflammation. In receiver operating characteristic curve analysis, PC ae C44:6 equaled CSF cell count in the ability to distinguish bacterial meningitis from viral meningitis/encephalitis and autoimmune CNS disorders (AUC 0.93 both), but had higher sensitivity (91% vs. 41%) and negative predictive value (98% vs. 89%). A diagnostic algorithm comprising cell count, lactate and PC ae C44:6 had a sensitivity of 97% (specificity 87%) and negative predictive value of 99% (positive predictive value 61%) and correctly diagnosed three of four bacterial meningitis samples that were misclassified by cell count and lactate due to low values not suggestive of bacterial meningitis.

Conclusions

Increased CSF PC ae C44:6 concentrations in bacterial meningitis likely reflect ongoing CNS cell membrane stress or damage and have potential as additional, sensitive biomarker to diagnose bacterial meningitis in patients with less pronounced neuroinflammation.
Multi-omic serum biomarkers for prognosis of disease progression in prostate cancer
Authors: Kiebish Michael A. , Cullen Jennifer , Mishra Prachi , Ali Amina , Milliman Eric , Rodrigues Leonardo O. , Chen Emily Y. , Tolstikov Vladimir , Zhang Lixia , Panagopoulos Kiki , Shah Punit , Chen Yongmei , Petrovics Gyorgy , Rosner Inger L. , Sesterhenn Isabell A. , McLeod David G. , Granger Elder , Sarangarajan Rangaprasad , Akmaev Viatcheslav , Srinivasan Alagarsamy , Srivastava Shiv , Narain Niven R. , Dobi Albert
Published: January 2020

Background

Predicting the clinical course of prostate cancer is challenging due to the wide biological spectrum of the disease. The objective of our study was to identify prostate cancer prognostic markers in patients ‘sera using a multi-omics discovery platform.

Methods

Pre-surgical serum samples collected from a longitudinal, racially diverse, prostate cancer patient cohort (N = 382) were examined. Linear Regression and Bayesian computational approaches integrated with multi-omics, were used to select markers to predict biochemical recurrence (BCR). BCR-free survival was modeled using unadjusted Kaplan–Meier estimation curves and multivariable Cox proportional hazards analysis, adjusted for key pathologic variables. Receiver operating characteristic (ROC) curve statistics were used to examine the predictive value of markers in discriminating BCR events from non-events. The findings were further validated by creating a training set (N = 267) and testing set (N = 115) from the cohort.

Results

Among 382 patients, 72 (19%) experienced a BCR event in a median follow-up time of 6.9 years. Two proteins—Tenascin C (TNC) and Apolipoprotein A1V (Apo-AIV), one metabolite—1-Methyladenosine (1-MA) and one phospholipid molecular species phosphatidic acid (PA) 18:0-22:0 showed a cumulative predictive performance of AUC = 0.78 [OR (95% CI) = 6.56 (2.98–14.40),P < 0.05], in differentiating patients with and without BCR event. In the validation set all four metabolites consistently reproduced an equivalent performance with high negative predictive value (NPV; > 80%) for BCR. The combination of pTstage and Gleason score with the analytes, further increased the sensitivity [AUC = 0.89, 95% (CI) = 4.45–32.05,P < 0.05], with an increased NPV (0.96) and OR (12.4) for BCR. The panel of markers combined with the pathological parameters demonstrated a more accurate prediction of BCR than the pathological parameters alone in prostate cancer.

Conclusions

In this study, a panel of serum analytes were identified that complemented pathologic patient features in predicting prostate cancer progression. This panel offers a new opportunity to complement current prognostic markers and to monitor the potential impact of primary treatment versus surveillance on patient oncological outcome.
Malignant transformation of oral leukoplakia is associated with macrophage polarization
Authors: Weber Manuel , Wehrhan Falk , Baran Christoph , Agaimy Abbas , Büttner-Herold Maike , Öztürk Hatice , Neubauer Kristina , Wickenhauser Claudia , Kesting Marco , Ries Jutta
Published: January 2020

Background

Most oral squamous cell carcinomas (OSCC) occur on the basis of oral leukoplakias (OLP). The histologic degree of dysplasia is insufficient for the prediction of OLP malignant transformation. Immunologic parameters are gaining importance for prognostic assessment and therapy of cancer. M2 polarized macrophages were shown to be associated with OSCC progression and inferior prognosis. The current study aims to answer the question if OLP with malignant transformation into OSCC within 5 years differ from OLP without transformation regarding macrophage infiltration and polarization.

Methods

201 specimens (50 transforming OLP, 53 non-transforming OLP, 49 corresponding OSCC and 49 healthy oral mucosa controls) were processed for immunohistochemistry. Samples were stained for CD68, CD163 and CD11c expression, completely digitalized and computer-assisted cell counting was performed. Epithelial and subepithelial compartments were differentially assessed. Groups were statistically compared using the Mann–Whitney U-test. A cut-off point for the discrimination of transforming and non-transforming OLP was determined and the association between macrophage infiltration and malignant transformation was calculated using the Chi-square test (χ2test).

Results

Macrophage infiltration and M2 polarization in OLP with malignant transformation within 5 years was significantly increased compared to OLP without malignant transformation (p < 0.05). OSCC samples showed the highest macrophage infiltration and strongest M2 polarization (p < 0.05). Additionally, transforming OLP revealed a significant shift of macrophage infiltration towards the epithelial compartment (p < 0.05). χ2test revealed a significant association of increased macrophage infiltration with malignant transformation (p < 0.05).

Conclusion

Immunological changes precede malignant transformation of OLP. Increased macrophage infiltration and M2 polarization was associated with the development of oral cancer in OLP. Macrophage infiltration could serve as predictive marker for malignant transformation.
Correction to: A suite of automated tools to quantify hand and wrist motor function after cervical spinal cord injury
Authors: Grasse Katelyn M. , Hays Seth A. , Rahebi Kimiya C. , Warren Victoria S. , Garcia Elizabeth A. , Wigginton Jane G. , Kilgard Michael P. , Rennaker Robert L.
Published: January 2020

The original article [1] contains several errors which the authors would like to rectify:
Future treatments for hereditary hemorrhagic telangiectasia
Authors: Robert Florian , Desroches-Castan Agnès , Bailly Sabine , Dupuis-Girod Sophie , Feige Jean-Jacques
Published: January 2020

Hereditary Hemorrhagic Telangiectasia(HHT), also known as Rendu-Osler syndrome, is a genetic vascular disorder affecting 1 in 5000–8000 individuals worldwide. This rare disease is characterized by various vascular defects including epistaxis, blood vessel dilations (telangiectasia) and arteriovenous malformations (AVM) in several organs. About 90% of the cases are associated with heterozygous mutations ofACVRL1orENGgenes, that respectively encode a bone morphogenetic protein receptor (activin receptor-like kinase 1, ALK1) and a co-receptor named endoglin. Less frequent mutations found in the remaining 10% of patients also affect the geneSMAD4which is part of the transcriptional complex directly activated by this pathway. Presently, the therapeutic treatments for HHT are intended to reduce the symptoms of the disease. However, recent progress has been made using drugs that target VEGF (vascular endothelial growth factor) and the angiogenic pathway with the use of bevacizumab (anti-VEGF antibody). Furthermore, several exciting high-throughput screenings and preclinical studies have identified new molecular targets directly related to the signaling pathways affected in the disease. These include FKBP12, PI3-kinase and angiopoietin-2. This review aims at reporting these recent developments that should soon allow a better care of HHT patients.
A new phenothiazine-based selective visual and fluorescent sensor for cyanide
Authors: Al-Zahrani Fatimah A. M. , El-Shishtawy Reda M. , Asiri Abdullah M. , Al-Soliemy Amerah M. , Mellah Khloud Abu , Ahmed Nahed S. E. , Jedidi Abdesslem
Published: January 2020

A new donor-π-acceptor derived from phenothiazine, namely 2-(2-((10-hexyl-10H-phenothiazin-3-yl)methylene)-3-oxo-2,3-dihydroinden-1-ylidene) malononitrile (PTZON) was synthesized and fully characterized, and its potential as a fluorescent sensor for cyanide anion was investigated. The PTZON showed a visible absorption band at 564 nm corresponds to an intramolecular charge transfer (ICT) and an emission band at 589 nm in CH3CN/H2O. The results of cyanide anion titration revealed ratiometric changes in both absorption and fluorescence spectra as a result of the nucleophilic addition of cyanide anion via Michael addition. The optical studies, FT-IR spectra, NMR, high-resolution mass, and DFT calculations confirmed the sensing mechanism. The selectivity of PTZON as a cyanide anion fluorescent sensor was proved in mixed solvent solutions, and the sensitivity was as low as 0.011 µM, which is far lower than the value allowed by the United States Environmental Protection Agency for drinking water (1.9 µM). Also, the detection limit of PTZON was assessed to be 3.39 μM by the spectrophotometric method. The binding stoichiometry between PTZON and cyanide anion was found to be 1:1 as evidenced by mass spectra. TLC silica-coated plates test strips demonstrated the fluorescent detection of cyanide anion.
Barriers to treatment optimization and achievement of patients’ goals: perspectives from people living with rheumatoid arthritis enrolled in the ArthritisPower registry
Authors: Gavigan Kelly , Nowell W. Benjamin , Serna Mylene S. , Stark Jeffrey L. , Yassine Mohamed , Curtis Jeffrey R.
Published: January 2020

Background

Few studies have investigated patients’ own treatment goals in rheumatoid arthritis (RA). The objective of this real-world, cross-sectional study of US patients with RA was to identify factors that patients believed influenced their physician’s treatment decisions. Secondary objectives included reasons patients tolerated sub-optimal disease control and their perceived barriers to treatment optimization.

Methods

Eligible participants were enrolled in the ArthritisPower registry, ≥ 19 years, had physician-diagnosed RA, unchanged treatment within 3 months of baseline, prior/current disease-modifying antirheumatic drug treatment (DMARDs), and computer/smartphone access. In December 2017, participants completed Patient-Reported Outcomes Measurement Information System-Computerized Adaptive Tests (PROMIS-CAT) for pain interference, fatigue, sleep disturbance, and physical function. Routine Assessment of Patient Index Data 3 (RAPID3) provided disease activity scores (0–30). Participants completed an online survey on barriers to treatment optimization, including self-perception of disease compared to RAPID3/PROMIS scores.

Results

A total of 249 participants met inclusion criteria and completed the survey. Mean age (SD) was 52 (11) years, and the majority were female (92%) with high RAPID3 disease activity (175/249 [70%]; median score 18). The main reason participants did not change treatment was their physician’s recommendation (66%; n = 32). Of participants with high RAPID3 disease activity, 66 (38%) were offered a treatment change; 19 (29%) of whom declined the change. Most participants who intensified treatment did so because their symptoms had remained severe or worsened (51%; n = 33); only 16 (25%) participants intensified because they had not reached a specified treatment goal. Among participants who self-reported their disease activity as “none/low” or “medium” (n = 202; 81% of cohort), most still had RAPID3 high disease activity (137/202 [68%]; score > 12). Most PROMIS scores showed moderate agreement with participants’ self-assessment of health status, in contrast to RAPID3 (weighted kappa: 0.05 [95% CI − 0.01, 0.11]).

Conclusions

Most participants trusted their rheumatologist’s treatment decisions and prioritized their physician’s treatment goals over their own. Patients should be encouraged to share their treatment goals/expectations with their rheumatologist, in line with the treat-to-target approach. RAPID3 may be inappropriate for setting patient-centric treatment goals given the poor agreement with self-reported disease activity; most PROMIS scores showed better alignment with patients’ own assessments.
Automatic load sharing of distribution transformer for overload protection
Authors: Nebey Abraham Hizkiel
Published: January 2020

Objective

Load sharing provides sufficient protection to distribution transformer under overloaded conditions. Due to overload on transformer, the efficiency drops and windings get overheated and may burn. By sharing a load current on transformer for each phase the transformer was protected. Therefore, the objective of this study was to protect transformers from overloaded conditions by sharing the load.

Result

The system automatically connects and disconnects switch to share the transformer loads. The controller was managed the load according to rules.
Does training location matter? Evidence from a randomized field experiment in Rural Indonesia
Authors: Pratiwi Ayu , Suzuki Aya
Published: January 2020

Informal network helps disseminate agricultural knowledge in the rural area where formal extension is lacking. However, how the interplay between formal training and informal network promotes technology adoption is still under-studied. This paper aims to examine the effects of training locations upon knowledge and adoption of agricultural techniques via strengthened informal and formal social networks. We administer agricultural training of identical contents in farmers’ hometown and in more remote but advanced locations and arrange farmers to travel to the respective locations. Then, we examine locational heterogeneity effects upon conservation and plant-rehabilitation techniques, and social network variables with formal extension services, informal network, and between participants and non-participants. Only farmers trained in the most remote location increase the size and depth of social network with their peers, extension expert, and non-participants upon returning from training. These changes in social networks may encourage them to adopt the technology. While formal training is important for knowledge diffusion, informal network is the key for successful adoption, and these networks are strengthened via training held in the most remote location.
Role of absence in academic success: an analysis using visualization tools
Authors: Etemadpour Ronak , Zhu Yongcheng , Zhao Qizhi , Hu Yilun , Chen Bohan , Sharier Mohammed Asif , Zheng Shirong , S. Paiva Jose Gustavo
Published: January 2020

Understanding the academic performance of students in colleges is an essential topic in Education research field. Educators, program coordinators and professors are interested in understanding how students are learning specific topics, how specific topics may influence the learning of other topics, how students’ grades/attendances in each course may represent important indicators to measure their performance, among other tasks. The use of data visualization and analytics is expanding in education institutions to perform a variety of tasks related to data processing and gaining into data-informed insights. In this paper, we present a visual analytic tool that combines data visualization and machine learning techniques to perform some visual analysis of students’ data from program courses. Two educational data collections were used to guide the creation of i) predictive models employing a variety of well known machine learning strategies, attempting to predict students’ future grade based on grade and attendance previous semesters and ii) a set interactive layouts that highlight the relationship between grades and attendance, also including additional variables such as gender, parents education level, among others. We performed several experiments, also using these data collections, to evaluate the layouts ability of highlighting interesting patterns, and we obtained promising results, demonstrating that such analysis may help the education experts to understand deficiencies on course structures.
Bacterial cytochrome P450-catalyzed regio- and stereoselective steroid hydroxylation enabled by directed evolution and rational design
Authors: Zhang Xiaodong , Peng Yaqin , Zhao Jing , Li Qian , Yu Xiaojuan , Acevedo-Rocha Carlos G. , Li Aitao
Published: January 2020

Steroids are the most widely marketed products by the pharmaceutical industry after antibiotics. Steroid hydroxylation is one of the most important functionalizations because their derivatives enable a higher biological activity compared to their less polar non-hydroxylated analogs. Bacterial cytochrome P450s constitute promising biocatalysts for steroid hydroxylation due to their high expression level in common workhorses like Escherichia coli. However, they often suffer from wrong or insufficient regio- and/or stereoselectivity, low activity, narrow substrate range as well as insufficient thermostability, which hampers their industrial application. Fortunately, these problems can be generally solved by protein engineering based on directed evolution and rational design. In this work, an overview of recent developments on the engineering of bacterial cytochrome P450s for steroid hydroxylation is presented.
General election effect on the network topology of Pakistan’s stock market: network-based study of a political event
Authors: Memon Bilal Ahmed , Yao Hongxing , Tahir Rabia
Published: January 2020

To examine the interdependency and evolution of Pakistan’s stock market, we consider the cross-correlation coefficients of daily stock returns belonging to the blue chip Karachi stock exchange (KSE-100) index. Using the minimum spanning tree network-based method, we extend the financial network literature by examining the topological properties of the network and generating six minimum spanning tree networks around three general elections in Pakistan. Our results reveal a star-like structure after the general elections of 2018 and before those in 2008, and a tree-like structure otherwise. We also highlight key nodes, the presence of different clusters, and compare the differences between the three elections. Additionally, the sectorial centrality measures reveal economic expansion in three industrial sectors—cement, oil and gas, and fertilizers. Moreover, a strong overall intermediary role of the fertilizer sector is observed. The results indicate a structural change in the stock market network due to general elections. Consequently, through this analysis, policy makers can focus on monitoring key nodes around general elections to estimate stock market stability, while local and international investors can form optimal diversification strategies.
Process intensification technologies for CO2 capture and conversion – a review
Authors: Adamu Abdullahi , Russo-Abegão Fernando , Boodhoo Kamelia
Published: January 2020

With the concentration of CO2in the atmosphere increasing beyond sustainable limits, much research is currently focused on developing solutions to mitigate this problem. Possible strategies involve sequestering the emitted CO2for long-term storage deep underground, and conversion of CO2into value-added products. Conventional processes for each of these solutions often have high-capital costs associated and kinetic limitations in different process steps. Additionally, CO2is thermodynamically a very stable molecule and difficult to activate. Despite such challenges, a number of methods for CO2capture and conversion have been investigated including absorption, photocatalysis, electrochemical and thermochemical methods. Conventional technologies employed in these processes often suffer from low selectivity and conversion, and lack energy efficiency. Therefore, suitable process intensification techniques based on equipment, material and process development strategies can play a key role at enabling the deployment of these processes. In this review paper, the cutting-edge intensification technologies being applied in CO2capture and conversion are reported and discussed, with the main focus on the chemical conversion methods.
Traditional festive food and fragile aspirations of development in Italy: the case of agnolotti pasta
Authors: Fontefrancesco Michele F.
Published: January 2020

This research draws from memories, and the deep sense of belonging, tradition, and presence that is linked with a dish of Italian regional tradition; agnolotti pasta, one example of what can be considered an Italian ethnic food. It does so in order to challenge an assumption that is widely spread in the public debate and as well as in scholarship, which automatically links the popularization of traditional, ethnic cuisine with a fulgid prospective of local development in particular for the rural communities. This article challenges this imagery by drawing attention on what popularization means and how it is achieved in food festivals, restaurants, and shops. In doing so, it contributes to decouple popularization and development by exploring the ethnographic case of Piedmont, Italy.
O contrato de seguro de responsabilidade civil para diretores e gestores na administração pública direta no Brasil
Authors: Martins Alexandre Marques da Silva , Pellanda Osiris Vargas
Published: January 2020

Directors and Officers Liability Insurance (D&O) contracted by the direct public administration in Brazil O presente artigo pretende oferecer uma análise sobre os aspectos relacionados com a contratação de seguros de responsabilidade civil para diretores e gestores públicos (D&O) pela administração pública direta no Brasil. Neste contexto, proceder-se-á a uma investigação dos fundamentos do seguro de responsabilidade civil que, por conseguinte, permitirá esclarecer as nuances do D&O cujos beneficiários são diretores e agentes públicos que gozam de alta discricionariedade em processos decisórios. Assim, será demonstrado que, se um governo deseja utilizar de maneira eficiente o D&O, que é uma ferramenta de gerenciamento de risco, é necessária não só a aplicação da análise econômica do direito e de princípios de governança corporativa, mas também de princípios que regem a administração pública em seus negócios jurídicos. This article aims to analyze the Directors and Officers Liability Insurance (D&O) contracted by the direct public administration in Brazil. In this context, an understanding of the underpinnings of civil liability insurance sheds light on the nuances of the D&O, whose beneficiaries are usually managers and public agents enjoying high-discretion decision-making power. Hence, this study will demonstrate that if a government wishes to make efficient use of D&O, a risk management tool, it is necessary to apply not only the Economic Analysis of the Law and principles of corporate governance but also general principles governing the public administration in its transactions.
A urbanidade como dever funcional no direito administrativo brasileiro
Authors: Dantas Fabiana Santos
Published: January 2020

A urbanidade é um termômetro que permite perceber como determinada sociedade, em determinado contexto e época, percebe a autoridade, o serviço público e a relação entre instituições estatais e o cidadão. Exigir um comportamento adequado do servidor à missão e aos limites da sua competência legal como forma de garantir a correta prestação do serviço é uma forma de incrementar a produtividade e a eficiência, além de preservar a boa imagem das instituições, e que também contribui para aperfeiçoar a conduta do servidor em todos os aspectos de sua vida funcional e privada. A metodologia de pesquisa consistiu em pesquisa bibliográfica, realizada por meio da análise de livros, artigos científicos, de revista e pesquisa documental quanto à legislação específica.Civility is a thermometer that indicates how society, in a specific contexto and at a specific time, perceives authority, public service and the relationship between citizens and public institutions. Demanding from public servants a standard of behavior that is appropriate to their mission and the limits of their legal competence, as a means of ensuring that they do their jobs properly, is a way to increase productivity and efficiency and preserve the reputation of an institution; and it also helps improve the public servant’s behavior in all aspects of their work and private life. The research methodology consisted of an analysis of books, scientific articles and magazines, and documentary research relative to specific legislation.