jimnoneill/paper-to-field-training huggingface dataset:
CHAPTER 11. The Importance of Kinase Mutations in Cancer Drug Discovery

Amino acid mutations within a kinase sequence may play a pivotal role on the behaviour of these proteins in various disease settings. These mutations in some cases can activate a kinase, commonly referred to as driver mutations and have become targets of drug discovery projects resulting in numerous approved therapies. In other cases, kinase mutations have been observed as a resistance mechanism to cancer treatments, in some cases such mutations have themselves become the target of future targeted drug discovery efforts leading to multiple generations of therapy. This chapter summarises the broad role of kinase mutations in drug discovery and reflects on the unique opportunities and challenges in the field. To highlight this fascinating area, specific examples including EGFR, ABL, RET, ALK, BRAF, cKIT and TRK are reported as case studies.

Topic: Lung Cancer Treatments and Mutations
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Smoking Related Changes in Neurotransmitters in African Americans

Smoking is a most common way of tobacco consumption that provides a pleasurable effect by modulating neurotransmitters in the brain. African Americans (AA) have shown higher susceptibility to nicotine consumption and highest rate of mortality due to cancer. In this study we have examined the levels of 6 neurotransmitters in AA smokers and compared them with nonsmokers of same population. We observed decrease in plasma levels of glutamate and increase in serotonin, epinephrine and dopamine. The level of gamma amino butyric acid (GABA) and norepinephrine was not changed significantly. The results, in part, explain the basis of higher nicotine susceptibility in AAs and will be helpful to develop population specific strategies for smoking cessation.

Topic: Nicotinic Acetylcholine Receptors Study
Subfield: Molecular Biology
Field: Biochemistry, Genetics and Molecular Biology
Domain: Life Sciences
Bullous pyoderma as a presentation of acute leukaemia

A patient with an unusual bullous pyoderma preceding the onset of acute leukaemia is reported. The initial lesions were purplish bullae, which later formed superficial ulcers and healed with minimal scarring. Histology showed intra-epidermal bullae with a dense polymorphonuclear infiltrate in the epidermis. This eruption is difficult to classify, but fifteen patients with similar skin lesions have been found in the literature, seven of these patients developed acute leukaemia and one had metastatic adenocarcinoma on presentation. We feel that the recognition of these distinctive skin lesions may be important because of their association with internal malignancy.

Topic: Autoimmune and Inflammatory Disorders
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Epimerization of chenodeoxycholic acid to ursodeoxycholic acid by Clostridium baratii isolated from human feces

Ursodeoxycholic acid-producing bacteria are of clinical and industrial interest due to the multiple beneficial effects of this bile acid on human health. This work reports the first isolation of 7-epimerizing bacteria from feces of a healthy volunteer, on the basis of their capacity to epimerize the primary bile acid, chenodeoxycholic acid, to ursodeoxycholic acid. Five isolates were found to be active starting from unconjugated chenodeoxycholic acid and its tauro-conjugated homologue, but none of these strains could epimerize the glyco-conjugated form. Biochemical testing and 16S ribosomal DNA sequencing converged to show that all five isolates were closely related to Clostridium baratii (99% sequence similarity), suggesting that this bacterial species could be responsible at least partially, for this bioconversion in the human gut.

Topic: Pediatric Hepatobiliary Diseases and Treatments
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Highly Sensitive in Vitro Diagnostic System of Pandemic Influenza A (H1N1) Virus Infection with Specific MicroRNA as a Biomarker

Several microRNAs (miRNAs) have been reported to be closely related to influenza A virus infection, replication, and immune response. Therefore, the development of the infectious-disease detection system using miRNAs as biomarkers is actively underway. Herein, we identified two miRNAs (miR-181c-5p and miR-1254) as biomarkers for detection of pandemic influenza A H1N1 virus infection and proposed the catalytic hairpin assembly-based in vitro diagnostic (CIVD) system for a highly sensitive diagnosis; this system is composed of two sets of cascade hairpin probes enabling to detect miR-181c-5p and miR-1254. We demonstrated that CIVD kits could not only detect subnanomolar levels of target miRNAs but also distinguish even single-base mismatches. Moreover, this CIVD kit has shown excellent detection performance in real intracellular RNA samples and confirmed results similar to those of conventional methods (microarray and quantitative real-time polymerase chain reaction).

Topic: Advanced biosensing and bioanalysis techniques
Subfield: Molecular Biology
Field: Biochemistry, Genetics and Molecular Biology
Domain: Life Sciences
A Commentary on L. V. Morrison, “On the Analysis of Megalithic Lunar Sightlines in Scotland”, Archaeoastronomy, Supplement of the Journal for the History of Astronomy, 1980, 2: 65–77

A Commentary on L. V. Morrison, "On the Analysis of Megalithic Lunar Sightlines in Scotland", Archaeoastronomy, Supplement of the Journal for the History of Astronomy, 1980, 2: 65-77

Topic: Archaeology and ancient environmental studies
Subfield: Paleontology
Field: Earth and Planetary Sciences
Domain: Physical Sciences
Covalent Immobilization of Tyrosinase on Electrospun Polyacrylonitrile/Polyurethane/Poly(<i>m</i>-anthranilic acid) Nanofibers: An Electrochemical Impedance Study

Polyacrylonitrile/polyurethane/poly(m-anthranilic acid) nanofibers were fabricated by electrospinning. Tyrosinase immobilization was performed by EDC/N-hydroxyl succinimide activation. Covalent binding of tyrosinase onto nanofibers was confirmed by Fourier transform infrared-attenuated total reflectance, and bicinchoninic acid assay revealed the amount of enzyme. Nanofiber morphology and composition were characterized by scanning electron microscopy/energy-dispersive X-ray spectroscopy (EDX). Nanofibers became smoother and thicker after tyrosinase immobilization. Effects of enzyme on nanofibers were investigated by electrochemical impedance spectroscopy and the data were fitted to equivalent electrical circuit model. EDX-mapping showed uniform distribution of enzyme. The solution resistance and charge transfer resistance of nanofibers decreased after enzyme immobilization.

Topic: Conducting polymers and applications
Subfield: Polymers and Plastics
Field: Materials Science
Domain: Physical Sciences
Renal denervation: current implications and future perspectives

SNS (sympathetic nervous system) activation is a common feature of arterial hypertension and has been demonstrated to contribute to the development and progression of the hypertensive state. Persuasive evidence suggests a strong association between SNS overactivity and variety of disease states, including chronic renal failure, insulin resistance, congestive heart failure, sleep apnoea, ventricular arrhythmias and others. Although sympatholytic agents are available to target SNS overactivity pharmacologically, they are not widely used in clinical practice, leaving the SNS unopposed in many patients. The recent introduction of catheter-based renal denervation as an alternative approach to target the SNS therapeutically has been demonstrated to result in a clinically relevant blood pressure reduction in patients with resistant hypertension, presumably through its effects on both efferent and afferent renal nerve traffic. Available data on this interventional procedure demonstrate a favourable vascular and renal safety profile. Preliminary data obtained primarily from small and mostly uncontrolled studies in related disease states often characterized by overactivity of the SNS are promising, but require confirmation in appropriately designed clinical trials. In the present paper, we briefly review the physiology of the renal nerves and their role in hypertension and other relevant disease states, summarize the data currently available from clinical studies pertaining to the safety and efficacy of renal denervation in resistant hypertension, discuss potential future implications and the available data supporting such a role for renal denervation, and describe some of the newer devices currently under investigation to achieve improved blood pressure control via renal denervation.

Topic: Blood Pressure and Hypertension Studies
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Search + Seizure: The Effectiveness of Interventions on SEO Campaigns

Black hat search engine optimization (SEO), the practice of abu-sively manipulating search results, is an enticing method to acquire targeted user traffic. In turn, a range of interventions—from mod-ifying search results to seizing domains—are used to combat this activity. In this paper, we examine the effectiveness of these inter-ventions in the context of an understudied market niche, counterfeit luxury goods. Using eight months of empirical crawled data, we identify 52 distinct SEO campaigns, document how well they are able to place search results for sixteen luxury brands, how this ca-pability impacts the dynamics of their order volumes and how well existing interventions undermine this business when employed. 1.

Topic: Consumer Market Behavior and Pricing
Subfield: Marketing
Field: Business, Management and Accounting
Domain: Social Sciences
Risk Assessment Based Maintenance Management for Distribution Network

Aiming at maintenance management of distribution network, this paper proposes a new maintenance technology based on risk assessment. It includes the procedure of risk assessment and the method of decision-making. The basic technical framework, which applies RBM to the maintenance management of distribution network is established. In the risk decision-making, the maintenance cost and maintenance profit concepts are introduced. With the help of risk assessment theory and interval analysis, the proposed technology is much more economical and operable. Application of the technology in an actual distribution network shows that it can evaluate the risk of equipment comprehensively and make decision-making quick and effective. Therefore, the technology proposed has good application prospect.

Topic: Evaluation and Optimization Models
Subfield: Safety, Risk, Reliability and Quality
Field: Engineering
Domain: Physical Sciences
Government Expenditure and Economic Growth in Nigeria

The study ascertained the effect of government expenditure on the economic growth of Nigeria. Specifically, the study assessed the effect of government capital expenditure, government recurrent expenditure and total government expenditure on the real gross domestic product of Nigeria. This study adopted an ex-post-facto research design. The data required for this study were collected from secondary sources, primarily from the Central Bank of Nigeria (CBN) Statistical Bulletin, and the National Bureau of Statistics (NBS). The key variables for which data were collected include government capital expenditure, government recurrent expenditure, and the real GDP of Nigeria. This study relies on time-series data covering the period from 1999 to 2023. Descriptive statistics was employed to summarize the key characteristics of the data. The primary method of test of hypotheses was the Ordinary Least Squares (OLS) regression technique. The study found that: government capital expenditure has a negative but non-significant effect on the real GDP of Nigeria, government recurrent expenditure has a positive but non-significant effect on the real GDP of Nigeria, total government expenditure has a positive and non-significant effect on the real GDP of Nigeria. In conclusion, the current structure or implementation of government spending may not be effectively aligned with mechanisms that drive sustained economic output. The study recommends that the Federal Ministry of Finance, Budget and National Planning should improve the planning, execution, and monitoring of capital projects to ensure that funds allocated for infrastructure and development projects are efficiently utilized and produce measurable economic impact.

Topic: Fiscal Policy and Economic Growth
Subfield: Economics and Econometrics
Field: Economics, Econometrics and Finance
Domain: Social Sciences
Factors Influencing the Development of Resistance in Escherichia Coli to the Sulfonamides

Summary The total resistance to a drug shown by a bacterium in a particular medium is defined in terms of the molar drug concentration required to inhibit the rate of growth by 50 per cent. A method of analysis is provided which permits any change in the total resistance to be assigned to either the bacterium (Rfb) or the environment (Rfe) in which the measurement of resistance is made. The application of this analysis to strains of E. coli trained to grow in media containing sulfanilamide showed the following. Strain trained on sulfanilamide in salt-glucose medium. Tested in salt-glucose medium, the increase in resistance was found to be 3-fold against both sulfanilamide and sulfathiazole. The same result was obtained when the strain was tested in peptone medium. Strain trained on sulfanilamide in peptone medium. Tested in salt-glucose medium, the strain showed a 3-fold increase in resistance to both sulfanilamide and sulfathiazole. Tested in peptone medium, however, it showed a 5.6-fold increase to sulfanilamide and a 21-fold increase to sulfathiazole. Strain trained on peptone medium, pH 7.8. Tested in salt-glucose medium, it showed little change in resistance. Tested in peptone medium it showed a 15-fold increase to the sulfanilamide and a 100-fold increase to sulfathiazole. It is concluded that the resistance of the bacterium not only depends upon the medium in which training occurred, but also upon the medium in which the measure of resistance is made. Furthermore, since the development of resistance to sulfanilamide does not always parallel that to sulfathiazole, it appears that the mode of action of these two drugs, though similar, is not identical.

Topic: Antibiotic Resistance in Bacteria
Subfield: Molecular Medicine
Field: Biochemistry, Genetics and Molecular Biology
Domain: Life Sciences
068 Depletion of the Microtubule Severing Enzyme Fidgetin-like 2 Promotes Nerve Regeneration and Improves Erectile Function in a Rodent Model of Radical Prostatectomy

Damage to the cavernous nerves (CN) during radical prostatectomy (RP) often causes erectile dysfunction (ED). We recently identified the microtubule (MT) regulatory protein fidgetin-like 2 (FL2) to be a promising therapeutic target for promoting cutaneous wound healing. We subsequently discovered that FL2 is also expressed in neurons, where it localizes to growth cones. Knockdown of FL2 in cultured neurons significantly enhanced the rate of axon growth, which led us to hypothesize that FL2 might be an effective target for enhancing nerve regeneration after injury. Here, using a rodent model of RP, we tested the hypothesis that local depletion of FL2 after cavernous nerve injury will promote nerve regeneration and improve erectile function. Three rat models of CN injury were used: mild (a smooth clamp applied for 2 minutes to the CN), moderate (a serrated clamp applied for 4 minutes to the CN) and severe (CN transection). After injury, a heparin sulfate microgel containing control- or FL2-siRNA was applied directly to the wound. Erectile function was assessed at several time points after injury by measuring the intracorporal pressure/blood pressure (ICP/BP) ratio following electro-stimulation of the CN. To study the effects of FL2 depletion on axon growth and on the microtubule cytoskeleton within the axon shaft, dissociated adult rodent dorsal root ganglion (DRG) neurons were transduced with AAV5 containing a plasmid encoding FL2 or scrambled small hairpin RNA (shRNA) and a GFP reporter. 5 days after treatment, neurons were replated for live monitoring of neurite growth, then fixed and immunostained for microtubules.

Topic: Nerve injury and regeneration
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Three-dimensional two-photon laser fabrication for metals, polymers, and magneto-optical materials

The three-dimensional (3D) two-photon laser fabrication techniques for metal, polymer, and magneto-optical structures are presented. Two-photon-induced reduction of metal complex ions was developed to create 3D metal micro/nano structures. Owing to the inhibition of unwanted growth of metal nano crystals using surfactant molecules, we have successfully improved the spatial resolution of fabricated metal structures down to 100 nm in linewidth. Arbitrary shaped 3D silver structures with high electric conductivity were fabricated. Two-photon-induced photopolymerization technique has been applied for the photonic wire bonding. We have demonstrated the optical interconnection of III-V based DFB lasers and photo detectors by polymer wires with optical coupling loss less than 0.3dB. We also applied two-photon laser irradiation technique for the modification of the magnetic properties of cerium-substituted yttrium iron garnet crystal (Ce<sub>x</sub>Y<sub>3-</sub>xFe<sub>5</sub>O<sub>12</sub>: Ce:YIG). A Ce:YIG layer was epitaxially-grown on a monomagnetic garnet (&lt;111&gt;-SGGG) substrate. 3D fs laser scanning in the Ce:YIG layer creates the micrometer patterns of both refractive index and magnetic properties change of the crystal. We demonstrated the micro/nanometer scale patterning of both optical and magnetic properties in the Ce:YIG crystal.

Topic: Nonlinear Optical Materials Studies
Subfield: Biomedical Engineering
Field: Engineering
Domain: Physical Sciences
The effect of vacuum ultraviolet irradiation on the time-dependent dielectric breakdown of organosilicate dielectrics

In this work, the effect of vacuum ultraviolet (VUV) exposure on the time-dependent dielectric breakdown (TDDB) properties of porous low-k films was investigated. Synchrotron irradiation was used to simulate the VUV photon irradiation from processing plasmas without any particle flux. The synchrotron flux varies with the wavelength, so the irradiation time was chosen to produce the same fluence at various photon energies. The deterioration of TDDB and generation of negative mobile charge were observed in the film after exposure to the VUV photons with 9 eV or higher energy. These effects were not observed in the films exposed with 7-eV photon energies or less. The creation of paramagnetic defects was observed with the ESR measurement and believed to be the reason for TDDB degradation. Depletion of carbon and breakage and rearrangement of the Si-O-Si structure were observed and believed to be the reason for mobile charge generation and the change in TDDB, chemical, and mechanical properties.

Topic: Semiconductor materials and devices
Subfield: Electrical and Electronic Engineering
Field: Engineering
Domain: Physical Sciences
Is immune checkpoint inhibition part of standard therapy for stage III non‐small cell lung cancer?

Decades of clinical trials investigating radiation dose modification and systemic therapy intensification have failed to improve outcomes in patients with unresectable stage III NSCLC. Treatment with durvalumab after chemoradiation improves progression free survival three‐fold compared to placebo with minimal increases in toxicity and represents a new standard of care for these patients.

Topic: Lung Cancer Diagnosis and Treatment
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Pterygium: A Hospital Based Study

Introduction:Pterygium is a non-malignant, slow growing, wing shaped proliferation of the fibro vascular tissue, which is arising from the sub-Conjunctival tissue, which may extend over the cornea and thus disturbing the vision.Background and Purpose: To assess the prevalence of Pterygium and Visual impairment in patients at a tertiary care centre of Etawah district.Methods: A cross-sectional study was done over a period of 3 months on both genders with the categorised age group and into grades according to the size of the Pterygium in the Department of Ophthalmology at UP University of Medical Sciences hospital Saifai, Etawah.After taking an informed consent a total of 2100 patient were examined by eye screening and diagnosed with the help of ophthalmologist in which 130 patients were found with Pterygium problem.Out of these 94 patients (135 eyes) was found purely with Pterygium in one or both eyes and the rest 36 were excluded because of other associated morbidities.The selected participants underwent assessment by eye examination sheet and the subject undergone specific test.The data were recorded on the basis of set predesigned, pretested, semi structured questionnaires and the grading was done with the help of slit lamp examination.The data was collected and analyzed using chi square test.Result and conclusion: A high prevalence of Pterygium was found in patients working in outdoor (76.29%) in comparison to indoor (23.70%) because of exposure to sunlight.

Topic: Corneal Surgery and Treatments
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
When You Can and Can’t See Double: Revisiting Focus Doubling in ASL

Focus doubling is a phenomenon that exists across various sign languages. In this paper, we focus on doubling in American Sign Language (ASL), and to a lesser extent, Brazilian Sign Language (Libras). In the doubling construction (1), one element of the sentence appears in its basegenerated

Topic: Hearing Impairment and Communication
Subfield: Developmental and Educational Psychology
Field: Psychology
Domain: Social Sciences
EPIDEMIOLOGICAL PROFILE OF HANSENÍASIS IN THE MUNICIPALITY OF PINHEIRO – MARANHÃO

Leprosy is an ancient pathology caused by an obligate intracellular microorganism, Mycobacterium leprae, which evolves slowly, manifesting itself through dermatoneurological signs and symptoms causing skin and peripheral nerve lesions. This is an epidemiological, descriptive, retrospective study, whose data collection came from diagnosed and notified leprosy cases in the municipality of Pinheiro - MA, from 2017 to 2021, in the online databases of the Information System of Notification Damages (SINAN) available from the SUS Department of Informatics (DATASUS). Leprosy cases in the municipality of Pinheiro, in the respective years, were a total of 188 reported cases. The year 2018 was the highest in terms of the incidence of cases, totaling 29.78% (56) of cases. In 2020, it recorded a lower incidence, totaling 14.36% (27) of cases, the highest notification occurred in individuals aged 30 to 39 years, totaling 39 cases. With regard to skin lesions, 44 of the reported cases occurred in patients with 2 to 5 lesions and 42 cases were greater than 5. The clinical form Dimorph was the largest identified during the period, with 80 cases. Of the 188 notifications, 119 progressed to cure and 12 dropped out. In view of the results, it was possible to trace the epidemiological profile of the disease, placing the elimination and control of leprosy as necessary.

Topic: Leprosy Research and Treatment
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences