Miracle-dz/UniFAR-FTUs huggingface dataset:
Daclatasvir plus Sofosbuvir with or without ribavirin in patients with chronic Hepatitis C genotype 3a in Pakistani population - A real world experience

Background and Objectives: Pakistan is among leading countries of world in prevalence of chronic hepatitis C Daclatasvir plus sofosbuvir is recommended for treatment of CHC. The purpose of study was to determine the sustained virological response in patients with chronic viral hepatitis C genotype 3a irrespective of previous treatment experience or presence of liver cirrhosis. Methods: Open label observational study was conducted at ABSTH Gujrat from January 2017 to April 2018 using non-probability purposive sampling. Patients chronically infected with hepatitis C virus having genotype 3a irrespective of presence of cirrhosis or previous treatment experience were included. Treatment naive patients without cirrhosis were given 12 weeks regimen of daily daclatasvir 60mg along with daily sofosbuvir 400mg. Patients with either compensated cirrhosis or treatment experienced were given 24 weeks regimen of daily daclatasvir 60mg along with daily sofosbuvir 400mg with weight based ribavirin. Data analysis was done using SPSS 20.0 Results: Total 125 patients were included in study out of which 42 (33.6%) were male and 83 (66.4%) were female. Early virological response and end treatment response was achieved by 124 (99.2%) patients. Twenty four patients were lost to further follow-up and SVR24 was available for 101(80.8%) patients out of which 48 were having cirrhosis and 53 were without cirrhosis. SVR24 was achieved by 96 patients (95%). Virological response was better in treatment naive patients and without cirrhosis compared to treatment experienced and those with cirrhosis. Conclusion: Daclatasvir plus sofosbuvir is an effective combination in patients with chronic hepatitis C genotype 3a infection.
An efficient and scalable method for the isolation of costatolide, a naturally-occurring anti-HIV agent, from the latex of Calophyllum teysmannii var. Inophylloide

An efficient and scalable method is reported for the isolation of costatolide (2), a naturally-occurring and HIV-1-specific non-nucleoside reverse transcriptase inhibitor, from the latex of Calophyllum teysmannii Miq. var. inophylloide (King.) P. F. Stevens (Clusiaceae). An overall yield of 10.6% of costatolide (2), with a purity of 96%, was obtained by repetitive recrystallization of the latex from a single organic solvent, subsequent to the pre-treatment of latex with hexane and dichloromethane to remove undesirable oily material. A second major component of the latex, soulattrolide (3), another HIV-1 non-nucleoside reverse transcriptase inhibitor, was also isolated. Both compounds were characterized by spectroscopic and chromatographic analyses and their in vitro anti-HIV activities were also confirmed. The results suggest that sufficient quantities of costatolide for preclinical and clinical development can be obtained in a relatively low-cost manner from the natural source.
Formalization of informal care in the Netherlands

In order to contain public care expenditure, policy makers in the Netherlands have over the last decades formulated in ever more stringent ways what ought to be expected from spouses, partners and family members with regard to care for dependent relatives. The current Dutch coalition cabinet plans to shift the principal responsibility for non-medical care, including demanding forms of care such as long-term personal care, to individuals and families. I argue that these policy developments imply cost redistribution rather than cost containment and that this redistribution is disadvantageous for women.
Repetitive Pitch Control for Vertical Axis Wind Turbine

Increasing demands in decentralized power plants have focused attention on Vertical Axis Wind Turbines (VAWTs). However, accessing high range of power from VAWTs is an impediment due to increased loads on the turbine blades. Here, we derive an optimal pitching action that reduces the periodic disturbance on turbine blades of VAWTs without affecting their power production. A control technique called Subspace Predictive Repetitive Control (SPRC) alongwith a LQ Tracker is used for recursive identification to estimate the parameters of VAWT model and further provide an optimal control law accordingly. Basis functions have been used to reduce the dimensionality of the control problem. Simulation results show a great potential of the data-driven SPRC approach coupled with LQ Tracker in reducing the turbine loads on VAWTs.
The effects of temperature on the proxies of visual detection of Danio rerio larvae: observations from the optic tectum

ABSTRACT Numerous studies have indicated that temperature improves the visual capabilities of different ectotherms, including a variety of fish species. However, none of these studies has directly tested whether elevated temperature extends the visual detection distance – the distance from which a visual stimulus is detected. To test this hypothesis, we investigated the effect of temperature on the visual detection distance of zebrafish (Danio rerio) larvae by measuring the largest distance from a moving target that induced a neural response in the optic tectum. We applied advanced methods of functional calcium imaging such as selective plane illumination microscopy in combination with a miniature OLED screen. The screen displayed an artificial, mobile prey, appearing in the visual field of the larvae. We performed experiments in three temperature treatments (18, 23 and 28°C) on transgenic fish expressing a fluorescent probe (GCaMP5G) that changes intensity in response to altered Ca2+ concentrations in the nerves in the optic tectum. Based on the obtained data, we also measured three additional parameters of the neural response in the optic tectum, each being a proxy of sensitivity to changes in the stimulus movement. We did not confirm our hypothesis, since the visual detection distance shortened as the temperature increased. Moreover, all of the three additional parameters indicated a negative effect of the temperature on the speed of the neural response to the stimuli. However, the obtained results could be explained not only by worse visual capabilities at the elevated temperature, but also by the differences in the visual field and in turn, the retinotopic location of the visual stimulus between the temperature treatments, since the stimulus in the experiments moved horizontally rather than forward and backward from the fish's eye. Summary: During the assessment of the visual detection distance of transgenic Danio rerio larvae in response to a visual stimulus using selective plane illumination microscopy, we found that the distance is shorter at elevated temperatures.
The Hippo in the room: Targeting the Hippo signalling pathway for osteosarcoma therapies

Osteosarcoma (OS) is a primary malignant bone tumour which usually occurs in children and adolescents. OS is primarily a result of chromosomal aberrations, a combination of acquired genetic changes and, hereditary, resulting in the dysregulation of cellular functions. The Hippo signalling pathway regulates cell and tissue growth by modulating cell proliferation, differentiation, and migration in developing organs. Mammalian STE20‐like 1/2 (MST1/2) protein kinases are activated by neurofibromatosis type 2, Ras association domain family member 2, kidney and brain protein, or other factors. Interactions between MST1/2 and salvador family WW domain‐containing protein 1 activate large tumour suppressor kinase 1/2 proteins, which in turn phosphorylate the downstream Yes‐associated protein 1/transcriptional coactivator with PDZ‐binding motif (YAP/TAZ). Moreover, dysregulation of this pathway can lead to aberrant cell growth, resulting in tumorigenesis. Interestingly, small molecules targeting the Hippo signalling pathways, through affecting YAP/TAZ cellular localisation and their interaction with members of the TEA/ATTS domain family of transcriptional enhancers are being developed and hold promise for the treatment of OS. This review discusses the existing knowledge about the involvement of the Hippo signalling cascade in OS and highlights several small molecule inhibitors as potential novel therapeutics.
RNAi-mediated mortality in Southern green stinkbug Nezara viridula by oral delivery of dsRNA.

BACKGROUND The southern green stinkbug, Nezara viridula (Hemiptera: Pentatomidae), is an important emerging polyphagous pest infesting soybean in the United States, Brazil and Argentina. The indiscriminate use of synthetic insecticides to control stinkbugs has limited the effectiveness of current management strategies. Alternatively, RNAi has emerged as a novel mode of action to control pests in an eco-friendly manner. RESULTS Here, we assessed the potential of RNAi technology by oral delivery of dsRNA for the control of N. viridula. First, ten candidate genes were tested by microinjection assay to select the best target genes for oral delivery. Seven genes resulted in more than 90% mortality after microinjection. To evaluate RNAi efficacy by oral delivery of dsRNA, five genes were tested by feeding the insects on gene-specific dsRNA mixed with an artificial diet. Significant mortality of 43% and 45% was observed after 14 days of treatment with dsαCop and dsvATPase A, respectively. To elucidate the lower RNAi efficacy via oral delivery of dsRNA, ex vivo dsRNA degradation in the saliva and the midgut juice was performed, which indicated that the reduced RNAi efficacy is accompanied by a rapid degradation of dsRNA by digestive secretions. CONCLUSION This study proves that RNAi can be triggered by orally delivered dsRNA in N. viridula and can be exploited to control this economically important pest. The reduced stability of dsRNA in saliva and midgut that was observed indicates a need to further improve RNAi efficacy, for example by use of specific formulations. This article is protected by copyright. All rights reserved.
The Stroman Effect: Participants in MEN Count, an HIV/STI Reduction Intervention for Unemployed and Unstably Housed Black Heterosexual Men, Define Its Most Successful Elements

Interventionists often prioritize quantitative evaluation criteria such as design (e.g., randomized controlled trials), delivery fidelity, and outcome effects to assess the success of an intervention. Albeit important, criteria such as these obscure other key metrics of success such as the role of the interactions between participants and intervention deliverers, or contextual factors that shape an intervention’s activities and outcomes. In line with advocacy to expand evaluation criteria for health interventions, we designed this qualitative study to examine how a subsample of Black men in MEN Count, an HIV/STI risk reduction and healthy relationship intervention with employment and housing stability case management for Black men in Washington, DC, defined the intervention’s success. We also examined the contextual factors that shaped participation in the study’s peer counseling sessions. We conducted structured interviews with 38 Black men, ages 18 to 60 years (M = 31.1, SD = 9.33) who completed at least one of three peer counseling sessions. Analyses highlighted three key themes: (a) the favorable impact of Mr. Stroman, the lead peer counselor, on participants’ willingness to participate in MEN Count and disclose their challenges—we dubbed this the “Stroman Effect”; (b) the importance of Black men intervention deliverers with relatable life experiences; and (c) how contextual factors such as the HIV/AIDS epidemic, needs for housing and employment services and safe spaces to talk about challenges, and absentee fathers shaped participation. We discuss the study’s implications for sustainable programs after funding ends and future multilevel health interventions to promote health equity for poor urban Black men.
Identification of patterns of tumour change measured on CBCT images in NSCLC patients during radiotherapy

In this study, we propose a novel approach to investigate changes in the visible tumour and surrounding tissues with the aim of identifying patterns of tumour change during radiotherapy (RT) without segmentation on the follow-up images. On-treatment cone-beam computed tomography (CBCT) images of 240 non-small cell lung cancer (NSCLC) patients who received 55 Gy of RT were included. CBCTs were automatically aligned onto planning computed tomography (planning CT) scan using a two-step rigid registration process. To explore density changes across the lung-tumour boundary, eight shells confined to the shape of the gross tumour volume (GTV) were created. The shells extended 6 mm inside and outside of the GTV border, and each shell is 1.5 mm thick. After applying intensity correction on CBCTs, the mean intensity was extracted from each shell across all CBCTs. Thereafter, linear fits were created, indicating density change over time in each shell during treatment. The slopes of all eight shells were clustered to explore patterns in the slopes that show how tumours change. Seven clusters were obtained, 97% of the patients were clustered into three groups. After visual inspection, we found that these clusters represented patients with little or no density change, progression and regression. For the three groups, the survival curves were not significantly different between the groups, p-value = 0.51. However, the results show that definite patterns of tumour change exist, suggesting that it may be possible to identify patterns of tumour changes from on-treatment CBCT images.
Rigidity in deafferented limbs

When the hirid limb of the cat is conipletely deafferented, it usually shows within forty-eight hours after the operation an overaction of the extensor muscles arid an exaggeration of the crossed extensor reflex. In my experience it often also shows an iiicreased resistance to passive flexion (Ranson, '28). Sometimes after a week or two, a condition of perinanent shortening or contracture of the extensor muscles may develop, and if this has occurred, the muscles fail to relax when the animal is deeply anesthetized. In order to cut the dorsal roots of the lumbosacral plexus in the cat it is necessary to open the dura, and it is not 130ssible to suture the dura again without producing pressure 011 the cord. Fo r this reason all investigators who have attempted this operation have left the dura open arid closed the ~vound by suturing the muscle over the cord. It is doubtful if under these conditions the cord can remain normsl. Obviously, the dorsal roots of the nerves entering into the formation of the brachial plexus a re better adapted for such experiments, because they can be divided without opening the dura. Recently we have perfornied this operation on seven cats. Tn three of them the dorsal roots were cut on one side from the fourth cervical to the second thoracic, inclusive; ill four others, from the fifth cervical to the second thoracic, inclusive. None of these cats developed the overaction of the extensor muscles characteristic of the conipletely deafierentcd hind leg. After section of the lurribosacral dorsal roots, a
Models for oscillations in plants

Ionic relations of plant cells comprise enzymes such as channels, pumps and co-transporters that catalyse the transition of ions through lipid membranes and, therefore, affect the membrane voltage. Since the activity of most of these enzymes is voltage dependent, these enzymes interact with each other via voltage changes. The temporal patterns of these interactions include oscillations. Models are presented here that simulate such oscillations based on physical properties of the ion transporters. Three oscillating scenarios are focussed on. Model A is adequate for short-term episodes. In model B, the external concentration of the ions is constant. This model, which applies e.g. to algae and single cells under experimental conditions, displays electric oscillations, just as model A, but also osmotic oscillations in which the internal ion concentrations play an essential role. Finally, model C applies to parenchyma cells in planta, where ion fluxes across the plasmalemma cause major concentration changes in the small apoplastic volume. In this model, internal and external buffering of ions is accounted for. For model C, it is assumed that the total quantities of substrates are constant, and portions of them are redistributed between different compartments. Oscillations of the model C are relatively rare. In most cases, model C approaches a steady state where K+ is in thermodynamic equilibrium.
Morfologia dos órgãos genitais do macho do Lobo marinho (Arctocephalus australis) e implicações biológicas

Male capacity for spreading genes to a great number of descendents and to determine population dynamics depend directly on the genital organs. Morphological studies in pinnipeds are scarce and the functional meaning of some characteristics has never been discussed. We hypothesized that Arctocephalus australis (A. australis) shows morphophysiological adaptations in order to guarantee the perpetuation of the species in the unique annual mating season. Seven males, dead from natural causes, had their genital organs collected and fixed for morphological description. Some features differ from other described mammalian males and are closely related to the biology and reproductive cycle of this species, as the scrotal epidermis, absence of glandular portion in the ductus deferens and spermatogenic epithelium suggest a recrudescent testis period. The corona glandis exhibits a singular arrangement: its erectile border looks like a formation of petals and its association with the os penis gives a "lily-flower" form to this region. We propose the name margo petaliformis to this particular erectile border of the corona glandis because of its similarity to a flower corola. The male genital organs of A. australis show morphological features compatible with adaptation to environment requirements and reproductive efficiency.
Essential oil of Tanacetum parthenium (L.) from East part of Kosova.

Problem statement: We have analyzed the chemical nature of essential oil of Tanacetum parthenium (L.) from East part of Kosova. Approach: The essential oil from aerial part of Tanacetum parthenium (L.), obtained by hidro-distillation was analyzed by GC and GC-MS. Results: Out of 25 peaks, 22 components, which constitute 88%, were identified in oil. The main compounds of Tanacetum parthenium (L.) from east region of Kosova, were camphor (63%) and camphene (9.6%). This study demonstrates the occurrence of camphor/camphene chemotype of Tanacetum parthenium (L.) from east part of Kosova. The present study showed the chemical composition of the hydro-distilled oil of Tanacetum parthenium (L.) from East part of Kosova and the results are compared to those reported in the literature. Conclusion: After comparison of our date with those reported in literature we can conclude that genetic and environmental factors play role in determining the composition of essential oil of Tanacetum parthenium (L.).
CLINICAL AND EXPERIMENTAL RESEARCH OF IMMUNOMODULATORY EFFECT OF AMISULPRIDE

Study of immunomodulatory effect of atypical antipsychotic amisulpride has revealed a positive clinical effect after 6-week therapy of schizophrenic patients regarding both positive and negative symptoms. A decrease in activity of humoral immunity factors ( В lymphocytes, immunoglobulins, HLA-DR + -cells) identified among schizophrenic patients in the process of amisulpride therapy can be attributed to a positive effect optimizing the ratio Th 1 /Th 2 . Amisulpride when used under experimental conditions produced a suppression of IgM-immune response in mice of the C57BL/6J strain. This effect was more expressed in animals with aggressive behavior pattern.
The Bark Beetle Complex Associated with Lodgepole Pine Slash in Alberta: Part 1—Notes on the Biologies of some Scolytidae attacking Lodgepole Pine Slash

This investigation was carried out to determine and explain some of the major factors underlying the variability in concentration of certain bark beetles in slash laid down under different cutting systems. Little is known on the life histories and natural control factors of many of the bark beetles inhabiting lodgepole pine (Pinus contorta Dougl. var latifolia Engelm.) and on the effect which different methods of logging have on the insects. Flash outbreaks in lodgepole pine stands frequently result from the breeding of certain bark beetles in slash remaining after logging operations. The opportunity to carry out this investigation was presented to the Calgary Laboratory in 1952, when the Federal Forest Service initiated studies on selectively cut lodgepole pine. This eventually became a co-operative project between the Federal Forest Service, Department of Northern Affairs and National Resources, and the Calgary Laboratories of Forest Zoology and Forest Pathology of the Division of Forest Biology.
How to reduce the delay of diagnosing secondary progression in multiple sclerosis

Unfortunately, an early recognition of transition from relapsing-remitting multiple sclerosis (RRMS) to secondary progressive multiple sclerosis (SPMS) and the stratification of RRMS patients with an increased risk of developing disease progression cannot be achieved to date.1 This remains a challenging point in the disease management of people with multiple sclerosis (MS). For this reason, the findings of Rojas et al.2 are of great scientific importance, as they could replicate the period of diagnostic uncertainty lasting approximately 3 years which has been already described by Katz Sand et al.3 Beyond clinical outcome markers, no definitive imaging or laboratory test informs exactly when a patient has entered the transitional MS phase.1 A diffuse transition phase where both RRMS and SPMS disease subtypes overlap for an undetermined period has been recently described. In this transition phase, a silent or hidden progression may occur, where several compensatory mechanisms may cover the disability progression under the ongoing neurodegenerative process. To monitor only structural integrity by applying imaging techniques or biomarkers will not be sufficient to detect this complex transition to SPMS. To help surmount such factors that contribute to diagnostic delay and underdiagnosis of progressive disease course, screening tools, such as the MS Progression Discussion (www.MSProDiscuss.com) tool,4 the MS prediction score,5 or the SPMS nomogram6 have been developed and are on their way into clinical practice. These technological resources represent a new generation of clinical tools for the daily neurological practice. We consider that relying in a well-performed supported anamnesis and quality description of the disability by the patient could bring important information missed behind the limited Expanded Disability Status Scale (EDSS) disease steps. Using quantitative and qualitative methods of its analysis, subtle signs and symptoms can be identified which are suggestive of progression to differentiate RRMS from early SPMS disease phase.7 Variables associated with the nature of the symptoms (e.g. intermittent vs persistent, stable vs worsening) and the presence of ambulatory, mobility, and cognitive symptoms were the most significantly associated to early SPMS. At the moment, the MSProDiscuss tool has been included in the PANGAEA Evolution and AMASIA clinical studies to generate prospective study data in clinical practice.8,9 We kindly suggest and are open to support Rojas et al. and Katz Sand et al. to implement such digital tools in their clinical practice as it could add a valuable resource and an additional point of view in the evaluation of this important group of MS patients.