Miracle-dz/UniFAR-FTUs huggingface dataset:
Actinic keratosis and imiquimod: a review of novel carriers and patents

ABSTRACT Introduction: Actinic keratosis is one of the most common disorder characterized by erythematic and generally attached scaly lesions which are present either alone or in clusters. World Health Organization defines actinic keratosis as a common intraepidermal neoplasm of sun-damaged skin, characterized by variable atypia of keratinocytes. Area covered: At the beginning of the 20th century, a new immunomodulator molecule, imiquimod, appears in the market for the treatment of actinic keratosis but suffers from the pitfalls of the conventional approach of dosage form preparation including high dose, poor stability and more side effects. The present article attempts to compile the scatter information related to actinic keratosis and imiquimod at one place. The special emphasis will be made on the information available in various research articles and patents with respect to the efforts made for overcoming shortcomings associated with imiquimod by novel drug delivery or other approaches. Expert opinion: The conventional drug delivery systems are unsuccessful to improve the actinic keratosis. The patient acceptance and compliance with these treatments are generally poor due to associated side effects, poor cosmetic outcomes and high costs. Therefore, several available and reported novel therapeutic approaches are being developed in order to provide better action.
A sandwich ELISA for detecting the hemagglutinin of avian influenza A (H10N8) virus

Novel influenza A virus (H10N8) infected human with fatality in China during 2013‐2014. It is important to detect such nonprevalent subtype influenza A virus in clinic and regular surveillance in the early stage for effective control and prevention from the potential pandemic. Unavailability of convenient rapid diagnosis for this subtype virus in resources‐limited setting is an obstacle for timely recognizing human case. In the present study, a panel of mouse H10 specific monoclonal antibodies (mAbs) was generated, two of which were used to develop a sandwich enzyme‐linked immunosorbent assay (ELISA) for detecting the hemagglutinin of avian influenza A (H10N8) virus. ELISA results showed high sensitivity with the lowest detection limit of 0.5HAU/50 μL for live virus, which laid a foundation for clinic use as a promising diagnostic methodology.
Endoplasmic Reticulum Stress Contributes to Mitochondrial Exhaustion of CD8+ T Cells

The PERK-mediated chronic stress axis contributes to the mitochondrial exhaustion that PD-1+CD8+ tumor-infiltrating T cells undergo. Targeting the PERK axis augments T-cell efficacy in tumors and aids anti-PD-1 therapy. Tumor antigen–specific T cells rapidly lose energy and effector function in tumors. The cellular mechanisms by which energy loss and inhibition of effector function occur in tumor-infiltrating lymphocytes (TILs) are ill-defined, and methods to identify tumor antigen–specific TILs that experience such stress are unknown. Processes upstream of the mitochondria guide cell-intrinsic energy depletion. We hypothesized that a mechanism of T-cell–intrinsic energy consumption was the process of oxidative protein folding and disulfide bond formation that takes place in the endoplasmic reticulum (ER) guided by protein kinase R-like endoplasmic reticulum kinase (PERK) and downstream PERK axis target ER oxidoreductase 1 (ERO1α). To test this hypothesis, we created TCR transgenic mice with a T-cell–specific PERK gene deletion (OT1+Lckcre+PERKf/f, PERK KO). We found that PERK KO and T cells that were pharmacologically inhibited by PERK or ERO1α maintained reserve energy and exhibited a protein profile consistent with reduced oxidative stress. These T-cell groups displayed superior tumor control compared with T effectors. We identified a biomarker of ER-induced mitochondrial exhaustion in T cells as mitochondrial reactive oxygen species (mtROS), and found that PD-1+ tumor antigen–specific CD8+ TILs express mtROS. In vivo treatment with a PERK inhibitor abrogated mtROS in PD-1+ CD8+ TILs and bolstered CD8+ TIL viability. Combination therapy enabled 100% survival and 71% tumor clearance in a sarcoma mouse model. Our data identify the ER as a regulator of T-cell energetics and indicate that ER elements are effective targets to improve cancer immunotherapy.
Phytochemistry of Three Ecuadorian Lamiaceae: Lepechinia heteromorpha (Briq.) Epling, Lepechinia radula (Benth.) Epling and Lepechinia paniculata (Kunth) Epling

In this research, the leaves of Lepechinia heteromorpha (Briq.) Epling, Lepechinia radula (Benth.) Epling and Lepechinia paniculata (Kunth) Epling have been collected in order to perform a phytochemical study. The first species was distilled to obtain a novel essential oil (EO), while the others were submitted to ethyl acetate extraction and secondary metabolite isolation. The chemical composition of the EO from L. heteromorpha has been investigated by Gas Chromatography-Mass Spectrometry (GC-MS) and Gas Chromatography with Retention Indices (GC(RI)), identifying 25 constituents. A major compound, (−)-ledol (21.2%), and a minor compound, (−)-caryophyllene oxide (1.0%), were isolated from the EO and their structures confirmed by Nuclear Magnetic Resonance (NMR) spectroscopy. Other major constituents of the EO were viridiflorene (27.3%), (E,E)-α-farnesene (1.4%), spirolepechinene and (E)-β-caryophyllene (7.1% each), allo-aromadendrene (6.1%), camphor (1.7%), limonene (1.3%) and β-phellandrene (4.6%). The enantiomeric composition of the EO monoterpene fraction was also studied, determining the enantiomeric excess and distribution of α-pinene, limonene, β-phellandrene and camphor. The ethyl acetate extract of L. radula and L. paniculata were fractionated by column chromatography. Spathulenol, angustanoic acid E and 5-hydroxy-4′,7-dimethoxy flavone were isolated from L. radula extract; ledol, guaiol and (−)-carnosol were found in L. paniculata.
Cost of Caregivers for Treating Hospitalized Diarrheal Patients in Bangladesh

INTRODUCTION Diarrheal diseases are a global public health problem and one of the leading causes of mortality, morbidity and economic loss. The objective of the study is to estimate the economic cost of caregivers and cost distribution per diarrheal episodes in Bangladesh. METHODS This was a cross-sectional hospital-based study conducted in public hospitals in Bangladesh. A total of 801 diarrheal patients were randomly selected and interviewed during January to December 2015. Simple descriptive statistics including frequencies, percentage, mean with 95% CI and median are presented. RESULTS The overall average cost of caregivers was BDT 2243 (US$ 28.58) while only BDT 259 (US$ 3.29) was spent as out of pocket payments. Caregivers mostly spent money (US$ 1.63) for food, lodging, utility bills, and other lump sum costs followed by the transportation costs (US$ 1.57). The caregivers spent more (US$ 44.45) when they accompanied the patients who were admitted in inpatients care and almost 3.6 times higher than for out-patients care (US$ 12.42). CONCLUSIONS The study delivers an empirical evidence to the health-care programmers and policy makers about the economic cost of caregivers during diarrheal treatment care, which should be accounted for in designing future diarrheal prevention programme.
Maternal obesity in pregnancy impacts offspring cardiometabolic health: Systematic review and meta‐analysis of animal studies

Obesity before and during pregnancy leads to reduced offspring cardiometabolic health. Here, we systematically reviewed animal experimental evidence of maternal obesity before and during pregnancy and offspring anthropometry and cardiometabolic health. We systematically searched Embase and Medline from inception until January 2018. Eligible publications compared offspring of mothers with obesity to mothers with a normal weight. We performed meta‐analyses and subgroup analyses. We also examined methodological quality and publication bias. We screened 2543 publications and included 145 publications (N = 21 048 animals, five species). Essential methodological details were not reported in the majority of studies. We found evidence of publication bias for birth weight. Offspring of mothers with obesity had higher body weight (standardized mean difference (SMD) 0.76 [95% CI 0.60;0.93]), fat percentage (0.99 [0.64;1.35]), systolic blood pressure (1.33 [0.75;1.91]), triglycerides (0.64 [0.42;0.86], total cholesterol (0.46 [0.18;0.73]), glucose level (0.43 [0.24;0.63]), and insulin level (0.81 [0.61;1.02]) than offspring of control mothers, but similar birth weight. Sex, age, or species did not influence the effect of maternal obesity on offspring's cardiometabolic health. Obesity before and during pregnancy reduces offspring cardiometabolic health in animals. Future intervention studies should investigate whether reducing obesity prior to conception could prevent these detrimental programming effects and improve cardiometabolic health of future generations.
RCVS2 score and diagnostic approach for reversible cerebral vasoconstriction syndrome

Objective To develop a method to distinguish reversible cerebral vasoconstriction syndrome (RCVS) from other large/medium-vessel intracranial arteriopathies. Methods We identified consecutive patients from our institutional databases admitted in 2013–2017 with newly diagnosed RCVS (n = 30) or non-RCVS arteriopathy (n = 80). Admission clinical and imaging features were compared. Multivariate logistic regression modeling was used to develop a discriminatory score. Score validity was tested in a separate cohort of patients with RCVS and its closest mimic, primary angiitis of the CNS (PACNS). In addition, key variables were used to develop a bedside approach to distinguish RCVS from non-RCVS arteriopathies. Results The RCVS group had significantly more women, vasoconstrictive triggers, thunderclap headaches, normal brain imaging results, and better outcomes. Beta coefficients from the multivariate regression model yielding the best c-statistic (0.989) were used to develop the RCVS2 score (range −2 to +10; recurrent/single thunderclap headache; carotid artery involvement; vasoconstrictive trigger; sex; subarachnoid hemorrhage). Score ≥5 had 99% specificity and 90% sensitivity for diagnosing RCVS, and score ≤2 had 100% specificity and 85% sensitivity for excluding RCVS. Scores 3–4 had 86% specificity and 10% sensitivity for diagnosing RCVS. The score showed similar performance to distinguish RCVS from PACNS in the validation cohort. A clinical approach based on recurrent thunderclap headaches, trigger and normal brain scans, or convexity subarachnoid hemorrhage correctly diagnosed 25 of 37 patients with RCVS2 scores 3–4 across the derivation and validation cohorts. Conclusion RCVS can be accurately distinguished from other intracranial arteriopathies upon admission, using widely available clinical and imaging features. Classification of evidence This study provides Class II evidence that the RCVS2 score accurately distinguishes patients with RCVS from those with other intracranial arteriopathies.
The lifetime prevalence of hospitalised head injury in Scottish prisons: A population study

Background There is mounting evidence that associates brain injury and offending behaviour, and there is a need to understand the epidemiology of head injury in prisoners in order to plan interventions to reduce associated disability and risk of reoffending. This is the first study to determine the lifetime prevalence of hospitalised head injury (HHI) in a national population of current prison inmates. In addition characteristics of prisoners with HHI and were compared to prisoners without HHI to discover whether those with HI differed demographically. Methods Whole life hospital records of everyone aged 35 years or younger and resident in a prison in Scotland on a census date in 2015 were electronically linked via their unique NHS identifier and checked for ICD-9 and 10 codes for head injury. Using a case-control design, these data were compared with a sample from the general population matched 3:1 for age, gender and area-based social deprivation. Comparison of demographic variables was made between prisoners with and without HHI. Results HHI was found in 24.7% (1,080/4,374) of prisoners and was significantly more prevalent than found in the matched general population sample (18.2%; 2394/13122; OR 2.10; 95%CI 1.87, 2.16). The prevalence of HHI in prisoners and controls was similar with the exception of a higher risk of HHI in prisoners in lower deprivation quintiles. Having three or more HHI was more common in prisoners (OR 3.04; 95%CI 2.33, 3.97) as were HHI with ICD codes for intracranial injuries (OR 1.81; 95% CI 1.54, 2.11), suggesting that more severe HHI is more prevalent in prisoners than the general population. The distributions within demographic variables and the characteristics of HHI admissions in prisoners with and without a history of HHI were similar. Conclusion Prisoners in Scotland aged 35 years or younger have a higher lifetime prevalence of HHI than the general population and are more likely to have had repeated HI or intracranial injuries. Further work is required to elucidate the correspondence between self-report of HI and hospitalised records and to ascertain persisting effects of HI in prisoners and the need for services to reduce associated disability and risk of reoffending.
Effect of EDTA, sodium, and calcium hypochlorite on the inorganic component of root canal dentin: A SEM analysis

This study evaluated the influence of canal irrigation protocols with 5.25% calcium hypochlorite [Ca(OCl)2], 5.25% sodium hypochlorite (NaOCl) and 17% EDTA solution on the inorganic component of root canal dentin. Sixty roots were randomly divided into six groups (n = 10): Saline solution (SS) (control); Saline solution (SSE) +17% EDTA; CH − 5.25% Ca(OCl)2; CHE − 5.25% Ca(OCl)2 + 17% EDTA; SH − 5.25% NaOCl; SHE − 5.25% NaOCl +17% EDTA. After canal irrigation, the specimens were longitudinally split and analyzed by scanning electron microscopy (SEM). Dentinal tubules were observed in transverse (middle and apical thirds) direction. The images were classified in scores, according to smear layer removal and peritubular dentin alteration, and data were analyzed by Kruskal–Wallis's test, followed by Dunn's test (α = 0.05). In the middle third, all groups with EDTA presented better removal of the smear layer with higher peritubular dentin alteration (p < .05). In the apical third, this happened only in SHE (p < .05). Ca(OCl)2 and NaOCl exhibit similar performance to remove smear layer and alteration of the inorganic component in the middle third. In the apical third, NaOCl associated with EDTA showed better performance in smear layer removal.
An Experimental Implementation of Action-Based Concurrency

This paper reports on an experimental implementation of action-based concurrent objects. Concurrency is expressed by allowing objects to have actions with a guard and a body, in addition to methods and variables. Condition synchronization is expressed by method guards protecting entry into an object. An action of an object can execute any time when its guard is true, with the restriction that at most one action or methods can execute within an object, thus guaranteeing atomicity. In principle, all objects can execute in parallel. The appeal of this model is that it is conceptually simple for programmers and comes with a verification and refinement theory based on atomic actions that is a straightforward extension of that for sequential programs. The concurrency model is suited for tightly coupled shared-memory processors. The implementation makes use of a recent thread library, NPTL, that supports a large number of kernel threads. Each active object has its own thread that cycles through the actions, evaluates their guards, and executes an enabled action. Syntactic constraints restrict when guards need to be re-evaluated. We compare the efficiency of the generated code with that of C/Pthreads, Ada, and Java using classical concurrency examples.
Brain‐machine interface of upper limb recovery in stroke patients rehabilitation: A systematic review

BACKGROUND Technologies such as brain-computer interfaces are able to guide mental practice, in particular motor imagery performance, to promote recovery in stroke patients, as a combined approach to conventional therapy. OBJECTIVE The aim of this systematic review was to provide a status report regarding advances in brain-computer interface, focusing in particular in upper limb motor recovery. METHODS The databases PubMed, Scopus, and PEDro were systematically searched for articles published between January 2010 and December 2017. The selected studies were randomized controlled trials involving brain-computer interface interventions in stroke patients, with upper limb assessment as primary outcome measures. Reviewers independently extracted data and assessed the methodological quality of the trials, using the PEDro methodologic rating scale. RESULTS From 309 titles, we included nine studies with high quality (PEDro ≥ 6). We found that the most common interface used was non-invasive electroencephalography, and the main neurofeedback, in stroke rehabilitation, was usually visual abstract or a combination with the control of an orthosis/robotic limb. Moreover, the Fugl-Meyer Assessment Scale was a major outcome measure in eight out of nine studies. In addition, the benefits of functional electric stimulation associated to an interface were found in three studies. CONCLUSIONS Neurofeedback training with brain-computer interface systems seem to promote clinical and neurophysiologic changes in stroke patients, in particular those with long-term efficacy.
Characterizing the structural variability of HIV-2 protease upon the binding of diverse ligands using a structural alphabet approach

Abstract The HIV-2 protease (PR2) is an important target for designing new drugs against the HIV-2 infection. In this study, we explored the structural backbone variability of all available PR2 structures complexed with various inhibitors using a structural alphabet approach. 77% of PR2 positions are structurally variable, meaning they exhibit different local conformations in PR2 structures. This variability was observed all along the structure, particularly in the elbow and flap regions. A part of these backbone changes observed between the 18 PR2 is induced by intrinsic flexibility, and ligand binding putatively induces others occurring in the binding pocket. These latter changes could be important for PR2 adaptation to diverse ligands and are accompanied by changes outside the binding pocket. In addition, the study of the link between structural variability of the pocket and PR2–ligand interactions allowed us to localize pocket regions important for ligand binding and catalytic function, regions important for ligand recognition that adjust their backbone in response to ligand binding and regions important for the pocket opening and closing that have large intrinsic flexibility. Finally, we suggested that differences in ligand effectiveness for PR2 could be partially explained by different backbone deformations induced by these ligands. To conclude, this study is the first characterization of the PR2 structural variability considering ligand diversity. It provides information about the recognition of PR2 to various ligands and its mechanisms to adapt its local conformation to bound ligands that could help understand the resistance of PR2 to its inhibitors, a major antiretroviral class. Communicated by Ramaswamy H. Sarma
Chimeric Antigen Receptor T-cell (CAR T) Therapy for Hematologic and Solid Malignancies: Efficacy and Safety—A Systematic Review with Meta-Analysis

Chimeric antigen receptors T cells (CAR T) had been used for treating various tumor patients in clinic, and owned an incredible efficacy in part of malignancies. However, CAR T therapy remains controversial due to doubts about its efficacy and safety in the clinical treatment of various malignancies. A total of 997 tumor patients from 52 studies were included in this review. Eligible studies were searched and reviewed from the databases of PubMed, Web of Science, Wanfang and Clinicaltrials.gov. Then meta-analysis and subgroup analysis were used to investigate the overall response rate (ORR), complete response rate (CRR), common side effect rate (CSER) and relapse rate (RR) of CAR T therapy for patients in clinical researches, respectively. The results further confirmed that CAR T therapy had a higher response rate for hematologic malignancies. More importantly, CAR T therapy had a higher CSER in patients with hematologic malignancies, and it had a similar RR in patients with different malignancies. Cell cultured without the addition of IL-2 and total administration less than 108 cells were recommended. This study offers a reference for future research regarding the application in solid and hematologic malignancies, side effects and relapse, and even the production processes of CAR T cells.
Video Stabilization Using Feature Point Matching

Video capturing by non-professionals will lead to unanticipated effects. Such as image distortion, image blurring etc. Hence, many researchers study such drawbacks to enhance the quality of videos. In this paper an algorithm is proposed to stabilize jittery videos. A stable output video will be attained without the effect of jitter which is caused due to shaking of handheld camera during video recording. Firstly, salient points from each frame from the input video is identified and processed followed by optimizing and stabilize the video. Optimization includes the quality of the video stabilization. This method has shown good result in terms of stabilization and it discarded distortion from the output videos recorded in different circumstances.
Optimization of Sequence, Display, and Mode of Operation of IgG-Binding Peptide Ligands to Develop Robust, High-Capacity Affinity Adsorbents That Afford High IgG Product Quality

This work presents the use of peptide ligand HWRGWV and its cognate sequences to develop affinity adsorbents that compete with Protein A in terms of binding capacity and quality of the eluted product. First, the peptide ligand was conjugated to crosslinked agarose resins (WorkBeads) at different densities and using different spacer arms. The optimization of ligand density and display resulted in values of static and dynamic binding capacity of 85 mg/mL and 65 mg/mL, respectively. A selected peptide-WorkBeads adsorbent was utilized for purifying Mabs from Chinese Hamster Ovary (CHO) cell culture supernatants. The peptide-WorkBeads adsorbent was found able to withstand sanitization with strong alkaline solutions (0.5 M NaOH). The purity of the eluted product was consistently higher than 95%, with logarithmic removal value (LRV) of 1.5 for host cell proteins (HCPs) and 4.0 for DNA. HCP clearance was significantly improved by adding a post-load washing step with either 0.1 M Tris HCl pH 9 or 1 M NaCl. The cognate peptide of HWRGWV, constructed by replacing arginine (R) with citrulline, further increased the HCP LRV to 2.15. The peptide-based adsorbent also showed a remarkable performance in terms of removal of Mab aggregates; unlike Protein A, in fact, HWRGWV was found to bind only monomeric IgG. Collectively, these results demonstrate the potential of peptide-based adsorbents as alternative to Protein A for the purification of therapeutic antibodies.