Miracle-dz/UniFAR-FTUs huggingface dataset:
ROS1 mutation non-small cell lung cancer—access to optimal treatment and outcomes

Introduction ROS1 oncogenic fusion, which was first identified by Rikova et al, is reported to be present in 1%–2% of non-small cell lung cancers (NSCLCs) and is defined as a distinct molecular sub-group. Crizotinib is very effective in ROS1-positive patients and is now Food and Drug Administration (FDA) approved for the treatment of patients with advanced ROS1-positive NSCLC. We report our experience in a tertiary cancer care hospital in India in ROS-1 positive patients. Materials and method The present series is a retrospective analysis of 22 patients from the prospectively maintained lung cancer audit. Demographic data were collected which included age, performance status, gender, stage, co-morbidities, sites of metastasis and smoking history. Data were also collected regarding the source of financing for crizotinib whether self-financed, through insurance or Non-Governmental Organisation (NGO) sponsored. Patients who had tested negative for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) and were subsequently found to be ROS1-mutation negative by fluorescence in situ hybridization (FISH) were evaluated on similar lines. All the data were entered and statistical analyses were performed using the SPSS software version 22.0. Response evaluation was done by RECIST 1.1 criteria. Results Between January 2015 and December 2017, there were 22 patients who were ROS1 positive from a total of 535 patients in whom ROS1 testing was performed. A total of 16 patients could receive crizotinib and 6 patients were never exposed to crizotinib. Among the 16 patients who received crizotinib, 2 (12.5%) achieved complete response (CR) as their best response and continue to remain in CR at follow-up. 13 (81%) had a partial response as best response and of which on follow-up 5 (38%) have progressed, while 8 (62%) continue to maintain response. The patients who were on crizotinib had good tolerance with none experiencing any grade 3/4 toxicity. The median follow-up of the entire cohort was 15.2 months in ROS1-positive cohort and 11.4 months in ROS1-negative cohort. In ROS1-positive cohort median, progression-free survival (PFS) was not reached and the estimated 2-year PFS was 54% and in ROS1-negative cohort, it was 5.1 months. The median overall survival of the entire ROS1-positive cohort was not reached and the estimated 1- and 2-year overall survival (OS) was 72% and 54%, respectively, and was 8.8 months in ROS1-negative cohort. Conclusion ROS1 rearrangement with an incidence of 4% of lung adenocarcinoma which is EGFR and ALK negative represents an important targetable driver mutation in the Indian population. Crizotinib also represents an effective treatment option with outcomes similar to those reported. Access to treatment remains an important roadblock to improve outcomes but innovative methods may improve access to these drugs.
Who Believes in ESP: Cognitive and Motivational Determinants of the Belief in Extra-Sensory Perception

Many people believe in extra-sensory perception, e.g. the ability to communicate with thoughts, to sense future events or locate radiation with the help of a V-shaped piece of wood. Addressing a gap in research specifically focused on ESP beliefs, we investigated cognitive styles and basic motivations related to these beliefs in two survey studies. The findings suggest that a propensity to use intuition is the best predictor of ESP beliefs in terms of cognitive style. ESP belief is positively related to fear of death, and this relation is partly mediated by fatalism, i.e. the belief that chance controls one’s life. ESP beliefs do not seem to be perceived as irreconcilable with a rational view of reality however, they do not necessarily provide psychological protection from existential concerns. The implications of the findings in terms of costs and benefits of these beliefs and the possibility to change them are discussed.
Chronic hepatitis B virus infection is associated with decreased serum 25(OH)D concentration in non-cirrhotic patients

Aim of the study Recent reports provide evidence for the immunomodulatory properties of vitamin D. Decreased vitamin D levels may contribute to the progression of liver disease in hepatitis B virus (HBV) infection. This study aims to assess serum 25(OH)D in patients with chronic HBeAg-negative HBV (CHB) infection at different phases of disease. Material and methods Fifty-eighty patients with CHB, 10 with a history of HBsAg/anti-HBs seroconversion, were enrolled. The control group consisted of 9 healthy volunteers. Serum 25(OH)D concentration was assessed by ELISA. Results Serum 25(OH)D concentration was significantly lower in the CHB group in comparison to the HC group. It did not differ across the consecutive phases of the HBeAg-negative HBV infection. Negative correlations between serum 25(OH)D and alanine aminotransferase (ALT) as well as frequency of peripheral blood monocytes were observed. Serum 25(OH)D in samples collected in winter was significantly lower in comparison to the pool of samples collected in the summer. Serum 25(OH)D concentration was not associated with the phases of HBV-infection, HBV viral load, APRI or liver histology. Conclusions Serum 25(OH)D is significantly decreased in HBV infection irrespectively of the phase of the infection and negatively correlates with serum ALT level, which may reflect the deterioration of liver function. Based on our results, we can conclude that the role of vitamin D in the immune control of HBV infection is probably irrelevant.
Knowledge and Attitudes Concerning Antibiotic Use and Resistance among the Public in Pulau Pinang, Malaysia

The aim of this cross-sectional study was to evaluate the knowledge and attitudes concerning antibiotic use and resistance among members of the local community in Pulau Pinang, Malaysia. The study was conducted among 326 residents of the Jelutong district, Pulau Pinang state, from August to October 2013. A self-administered five-part questionnaire was used for the data collection. The respondents exhibited inadequate knowledge of antibiotics in general. Approximately 80% of them did not know the indications for antibiotic use, while 76% believed that antibiotics were useful in terms of resolving viral fever. Additionally, 52.6% believed that antibiotics could be used to treat all types of infections. Inadequate knowledge of antibiotic resistance was also evident among the respondents, since 72.9% of them did not agree that resistant bacteria can spread from human or animal to human, while 32% were unaware that bacteria can develop resistance to antibiotics. More than 60% of respondents admitted that they took antibiotics in order to accelerate their recovery from illness, while 34.8% claimed that they only stopped taking antibiotics when they felt better. The findings hence indicate that most respondents had poor knowledge and attitudes concerning antibiotic use and resistance, which suggests the need for more community-based educational campaigns designed to improve the public’s knowledge and attitudes regarding antibiotics.
Metabolomics Profiling on Different Stages of Colorectal Cancer: A Systematic Review

Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. Early diagnosis and accurate staging of the disease is vital to improve the prognosis. Metabolomics has been used to identify changes in metabolite profiles in the different stages of cancer in order to introduce new non-invasive molecular tools for staging. In this systematic review, we aim to identify the common metabolite changes in human biological samples and the dominant metabolic pathways associated with CRC progression. A broad systematic search was carried out from selected databases. Four reviewers screened and reviewed the titles, abstracts, and full-text articles according to the inclusion and exclusion criteria. Quality assessment was conducted on the eight articles which met the criteria. Data showed that the metabolites involved with redox status, energy metabolism and intermediates of amino acids, choline and nucleotides metabolism were the most affected during CRC progression. However, there were differences in the levels of individual metabolites detected between the studies, and this might be due to the study population, sample preparation, analytical platforms used and statistical tools. In conclusion, this systematic review highlights the changes in metabolites from early to late stages of CRC. Moreover, biomarkers for prognosis are important to reduce CRC-related mortality.
Towards Comprehensive Spatial Development in Europe: A Critical View from Finland

This article critically examines how the assumptions about “comprehensive spatial development” are realised in the practices of zone-based development through a case study on regional development zones (RDZs) in Finland. In European spatial development, a zone-based framework that builds on connecting infrastructure (often referred to as a development corridor in an international context) has been discussed as a tool to promote both competitive and balanced development and to more efficiently utilise the existing infrastructure. Furthermore, in Finnish policy rhetoric, RDZs are seen as potential tools in developing simultaneously economically, socially and environmentally sustainable spatial structure. In the practices of regional development, however, these comprehensive goals are so far more aspirational than practised reality. There is a disconnection between the standard physical planning and new “soft” development framework, a disconnection between national and regional objectives, a lack of nationally coordinated policies, and a lagging completion of the institutional framework for comprehensive spatial development.
Serum Thyroglobulin: Preoperative Levels and Factors Affecting Postoperative Optimal Timing following Total Thyroidectomy

Objective We evaluated if preoperative TG levels affected postoperative levels and if other factors may influence the optimal time to check postoperative TG. Methods This is a prospective, observational pilot study. We approved and enrolled 50 subjects ≥ 19 years scheduled for total thyroidectomy and measured serum TG, thyroglobulin antibody (TG ab), and TSH preoperatively and post thyroidectomy at 7-14 days, 4 and 6 weeks, and 3 months in subjects with benign pathology, with additional 6- and 12-month measurements in subjects with thyroid cancer. Results Preoperative TG was significantly higher in the benign (median 167.5 ng/mL vs 30.8 ng/mL) than in the malignant (p = 0.0006) group. In the benign group, 76.5% (13/17) of subjects had an undetectable TG < 0.2 ng/mL by 12 weeks postoperatively. In the malignant group, 70.6% (12/17) of those who did not receive RAI therapy and 25% (1/4) of those who did receive RAI had undetectable TG < 0.2 ng/mL by 12 weeks. Subset analysis showed 94.1% (16/17) of the benign, 70.6% of the malignant without RAI, and 50% (2/4) of the malignant with RAI achieved TG < 1.0 ng/mL by 6 weeks postoperatively. Four subjects in the malignant group reached undetectable TG levels as early as 7-14 days postoperatively. Conclusion Preoperative TG levels did not predict the risk of malignancy nor time to TG nadir postoperatively. We did not find a difference in TG elimination half-life between the benign and malignant groups. The median time to reach undetectable TG levels in both benign and malignant groups who did not receive RAI therapy was 12 weeks. However, those with preexisting hypothyroidism and hyperthyroidism had lower levels of TG overall in the malignant group which can be taken into consideration besides other known factors that can affect TG levels post thyroidectomy. This trial is registered with Clinicaltrials.gov NCT02347683.
Increased Lower Limb Loading During Sit-to-Stand is Important for the Potential for Walking Progression in Ambulatory Individuals with Spinal Cord Injury

Background Decreased rehabilitation time may increase the need for walking devices at the time of discharge to promote levels of independence among ambulatory individuals with spinal cord injury (SCI). However, using walking devices could create adverse effects on patients. This study explores the proportion of walking devices used, potential for walking progression, and associated factors among ambulatory individuals with SCI. Methods Fifty-seven participants were assessed for their demographics and functional ability relating to the requirement for walking devices, including the Timed Up and Go Test (TUGT) and lower limb loading during sit-to-stand (LLL-STS). Results Thirty-five participants (61%) used a walking device, particularly a standard walker, for daily walking. More than half of them (n = 23, 66%) had potential of walking progression (i.e., safely walk with a less-support device than the usual one). The ability of walking progression was significantly associated with a mild severity of injury, increased lower-limb muscle strength, decreased time to complete the TUGT, and, in particular, increased LLL-STS. Conclusion A large proportion of ambulatory individuals with SCI have the potential for walking progression, which may increase their level of independence and minimise the appearance of disability. Strategies to promote LLL-STS are important for this progression.
The architectural design of smart ventilation and drainage systems in termite nests

Ventilation and drainage in termite nests are controlled by microscale morphological features of the outer walls. Termite nests have been widely studied as effective examples for ventilation and thermoregulation. However, the mechanisms by which these properties are controlled by the microstructure of the outer walls remain unclear. Here, we combine multiscale X-ray imaging with three-dimensional flow field simulations to investigate the impact of the architectural design of nest walls on CO2 exchange, heat transport and water drainage. We show that termites build outer walls that contain both small and percolating large pores at the microscale. The network of larger microscale pores enhances permeability by one to two orders of magnitude compared to the smaller pores alone, and it increases CO2 diffusivity up to eight times. In addition, the pore network offers enhanced thermal insulation and allows quick drainage of rainwater, thereby restoring the ventilation and providing structural stability to the wet nest.
Antidiabetic Effect of Monolluma quadrangula Is Mediated via Modulation of Glucose Metabolizing Enzymes, Antioxidant Defenses, and Adiponectin in Type 2 Diabetic Rats

Monolluma quadrangula is a succulent bush traditionally used to treat diabetes and peptic ulcer. The present study aimed to investigate the effect of M. quadrangula hydroethanolic extract on glucose tolerance, insulin sensitivity, glucose metabolizing enzymes, lipid profile, and adiponectin expression in type 2 diabetic rats. In addition, the study evaluated the antioxidant and anti-inflammatory activities of the M. quadrangula extract. Type 2 diabetes was induced by feeding rats a high-fat diet (HFD) for 8 weeks followed by 30 mg/kg streptozotocin (STZ). Diabetic rats received 300 or 600 mg/kg M. quadrangula extract for 4 weeks. HFD/STZ diabetic rats showed impaired glucose tolerance, reduced insulin secretion, and insulin resistance. HFD and STZ induced a significant increase in serum cholesterol, triglycerides and proinflammatory cytokines, and liver lipid peroxidation. Treatment with M. quadrangula extract ameliorated these metabolic disturbances and increased liver glycogen, hexokinase activity, and antioxidants. M. quadrangula declined the activity of liver glucose-6-phosphatase and fructose-1,6-biphosphatase. In addition, M. quadrangula extract increased serum adiponectin levels and hepatic adiponectin expression in HFD/STZ diabetic rats. In conclusion, M. quadrangula exerts antidiabetic effect mediated via ameliorating glucose tolerance, insulin sensitivity, glucose metabolizing enzymes, and antioxidant defenses. Increased adiponectin levels and expression seems to mediate, at least in part, the antidiabetic effect of M. quadrangula.
Mapping Gene Markers for Apple Fruit Ring Rot Disease Resistance Using a Multi-omics Approach

Apple fruit ring rot (FRR), caused by Botryosphaeria dothidea, is a worldwide disease that impacts Asian apple production regions. However, no substantial progress has thus far been made toward the mapping of candidate genes or the development of effective genetic makers. In this five-year study, the resistance of 1,733 F1 hybrids from the cross ‘Jonathan’ × ‘Golden Delicious’ was phenotyped by non-wounding inoculation with four B. dothidea isolates. We first conducted systematic comparison of different analytic strategies for bulk segregant analysis by re-sequencing (BSA-Seq) and obtained suitable one for outbreeding species such as Malus. Forty-six quantitative trait loci (QTL) for resistance/susceptibility to the four isolates, including one QTL ‘hotspot’ on chromosome 14, were identified via BSA-Seq. Using integrated multi-omics strategies including RNA-sequencing, parental re-sequencing, BSA-Seq and meta-analysis of RNA-sequencing, fifty-seven candidate genes and corresponding functional mutations from the QTL were predicted. Functional mutations located on the candidate genes were validated using kompetitive allele-specific PCR in hybrids and Malus germplasm accessions with extremely resistant/susceptible phenotypes. Ten effective markers for apple ring rot were developed. The results provide an example of rapid candidate gene mapping for complex traits in outbreeding species.
The Spectrum of Clinical and Urodynamic Findings in Patients with Spinal Tuberculosis Exhibiting Lower Urinary Tract Symptoms, before and after Spinal Surgical Intervention with Antitubercular Treatment: A Prospective Study

Study Design Observational study. Purpose This study aims to assess the clinical and urodynamic parameters in patients with spinal tuberculosis (TB) exhibiting lower urinary tract symptoms (LUTS) at the time of presentation and after spinal surgical intervention. Overview of Literature Variable urodynamic findings in patients with spinal TB. Methods We prospectively evaluated 10 patients with spinal TB exhibiting LUTS. Urinary symptoms were assessed by the American Urological Association (AUA) symptom score. We performed a urodynamic study (UDS), including electromyography, in all patients before and 3 months after spinal surgery. Results The mean age of patients was 29.7 years (range, 15–52 years), and the mean AUA symptom score was 12.5 and 11.8 before and after spinal surgery, respectively. Overall, five patients exhibited improvement in the AUA symptom score, and three showed no change, while two patients’ condition worsened. We observed detrusor overactivity (DO) in two patients, and detrusor sphincter dyssynergia (DSD) in four patients. In addition, high-pressure voiding (HPV) was noted in two patients. On follow-up after spinal surgery, DO and DSD exhibited no improvement. Although HPV resolved, two patients developed new-onset poor compliance with worsening DO and DSD. Furthermore, two patients had bilateral hydronephrosis before surgery, which resolved on follow-up. Conclusions Patients with spinal TB exhibiting LUTS can display a spectrum of clinical presentations and variable UDS findings. As two patients exhibited new onset poor compliance with bilateral hydronephrosis in one of them, this study concludes that a close follow-up for upper tracts in these patients is required despite successful spinal surgery.
Novel Flavivirus Antiviral That Targets the Host Nuclear Transport Importin α/β1 Heterodimer

Dengue virus (DENV) threatens almost 70% of the world’s population, with no effective vaccine or therapeutic currently available. A key contributor to infection is nuclear localisation in the infected cell of DENV nonstructural protein 5 (NS5) through the action of the host importin (IMP) α/β1 proteins. Here, we used a range of microscopic, virological and biochemical/biophysical approaches to show for the first time that the small molecule GW5074 has anti-DENV action through its novel ability to inhibit NS5–IMPα/β1 interaction in vitro as well as NS5 nuclear localisation in infected cells. Strikingly, GW5074 not only inhibits IMPα binding to IMPβ1, but can dissociate preformed IMPα/β1 heterodimer, through targeting the IMPα armadillo (ARM) repeat domain to impact IMPα thermal stability and α-helicity, as shown using analytical ultracentrifugation, thermostability analysis and circular dichroism measurements. Importantly, GW5074 has strong antiviral activity at low µM concentrations against not only DENV-2, but also zika virus and West Nile virus. This work highlights DENV NS5 nuclear targeting as a viable target for anti-flaviviral therapeutics.
Crosstalk of PD-1 signaling with the SIRT1/FOXO-1 axis during the progression of visceral leishmaniasis

ABSTRACT Previously, we documented the role of the programmed death-1 (PD-1, also known as PDCD1) pathway in macrophage apoptosis and the downregulation of this signaling during infection by the intra-macrophage parasite Leishmania donovani. However, we also found that, during the late phase of infection, PD-1 expression was significantly increased without activating host cell apoptosis; here we show that inhibition of PD-1 led to markedly decreased parasite survival, along with increased production of TNFα, IL-12, reactive oxygen species (ROS) and nitric oxide (NO). Increased PD-1 led to inactivation of AKT proteins resulting in nuclear sequestration of FOXO-1. Transfecting infected cells with constitutively active FOXO-1 (CA-FOXO) led to increased cell death, thereby suggesting that nuclear FOXO-1 might be inactivated. Infection significantly induced the expression of SIRT1, which inactivated FOXO-1 through deacetylation, and its knockdown led to increased apoptosis. SIRT1 knockdown also significantly decreased parasite survival along with increased production of TNFα, ROS and NO. Administration of the SIRT1 inhibitor sirtinol (10 mg/kg body weight) in infected mice decreased spleen parasite burden and a synergistic effect was found with PD-1 inhibitor. Collectively, our study shows that Leishmania utilizes the SIRT1/FOXO-1 axis for differentially regulating PD-1 signaling and, although they are interconnected, both pathways independently contribute to intracellular parasite survival. This article has an associated First Person interview with the first author of the paper. Summary: Leishmania parasites regulate PD-1 signaling through the SIRT1/FOXO-1 axis to inhibit host cell apoptosis to allow infection establishment during early and late phases of infection.
Losing the Arms Race: Greater Wax Moths Sense but Ignore Bee Alarm Pheromones

The greater wax moth, Galleria mellonella L. , is one of main pests of honeybees. The larvae burrow into the wax, damaging the bee comb and degenerating bee products, but also causes severe effects like driving the whole colony to abscond. In the present study, we used electroantennograms, a Y maze, and an oviposition site choice bioassay to test whether the greater wax moth can eavesdrop on bee alarm pheromones (isopentyl acetate, benzyl acetate, octyl acetate, and 2-heptanone), to target the bee colony, or if the bee alarm pheromones would affect their preference of an oviposition site. The results revealed that the greater wax moth showed a strong electroantennogram response to these four compounds of bee alarm pheromones even in a low concentration (100 ng/μL), while they showed the highest response to octyl acetate compared to the other three main bee alarm components (isopentyl acetate, benzyl acetate, and 2-heptanone). However, the greater wax moth behavioral results showed no significant preference or avoidance to these four bee alarm pheromones. These results indicate that bees are currently losing the arms race since the greater wax moth can sense bee alarm pheromones, however, these alarm pheromones are ignored by the greater wax moth.