Miracle-dz/UniFAR-FTUs huggingface dataset:
CRISPR/Cas9 genome-wide screening identifies KEAP1 as a sorafenib, lenvatinib, and regorafenib sensitivity gene in hepatocellular carcinoma

Sorafenib is the first-line drug used for patients with advanced hepatocellular carcinoma (HCC). However, acquired sorafenib resistance in cancer patients limits its efficacy. Here, we performed the first genome-wide CRISPR/Cas9-based screening on sorafenib-treated HCC cells to identify essential genes for non-mutational mechanisms related to acquired sorafenib resistance and/or sensitivity in HCC cells. KEAP1 was identified as the top candidate gene by Model-based Analysis of Genome-wide CRISPR/Cas9 Knockout (MAGeCK). KEAP1 disrupted HCC cells were less sensitive than wild-type cells in short- and long-term sorafenib treatments. Compared to wild-type cells, KEAP1-disrupted cells showed lower basal and sorafenib-induced reactive oxygen species (ROS) levels and were more resistant to oxidative stress-induced cell death. The absence of KEAP1 led to increased activity of Nrf2, a key transcription factor controlling antioxidant responses, as further evidenced by increased expression of Nrf2-controlled genes including NQO1, GPX2 and TXNRD1, which were positively associated with chemoresistance. In addition, KEAP1 disruption counteracted the reduction of cell viability and the elevation of ROS caused by lenvatinib, a drug that recently showed clinical efficacy as a first-line treatment for unresectable HCC. Finally, Keap1 disruption also increased the resistance of cells to regorafenib, a recently approved drug to treat HCC as a second line therapy. Taken together, our data indicate that deregulation of the KEAP1/Nrf2 pathway following KEAP1 inactivation contributes to sorafenib, lenvatinib, and regorafenib resistance in human HCC cells through up-regulation of Nrf2 downstream genes and decreased ROS levels.
Safety of veralipride for the treatment of vasomotor symptoms of menopause

ObjectiveVeralipride is a nonhormonal option for the treatment of vasomotor symptoms of menopause. Incidence of adverse events in a Mexican population and drug compliance according to correct use were evaluated. MethodsWe carried out a longitudinal, prospective, and analytical study in Mexican women who received veralipride to treat symptoms of menopause from 2011 to 2012. There were 386 treatment cycles; 272 were assigned to dosing schedule 1, which included 20 days of treatment with 10 days of suspension, and 114 were assigned to dosing schedule 2, which included 5 days of treatment and 2 days of suspension. ResultsA total of 57 adverse events were registered during the 386-month treatment. For the 20 × 10 dosing schedule, the highest incidence was observed for anxiety (2.2%), drowsiness, and weakness (1.5%); for the 5 × 2 dosing schedule, the highest incidence was observed for drowsiness (5.3%) and headache (2.6%). The Hamilton Depression Rating Scale was used to assess the presence and severity of depression; improvement was noted. The Unified Parkinson’s Disease Rating Scale was used to assess neurological movement disorders; no adverse neurological events were detected. Based on the assessments of both women and physicians, the highest frequency was observed for “very satisfied” (45.5% and 52.3%, respectively), followed by “satisfied” (23.9% and 27.3%, respectively). ConclusionsBoth dosing schedules show acceptable safety profiles for up to 6 months of use when used according to the contraindications in the current prescribing information for standard use (2012) and recent medical literature.
Understanding Attack Trends from Security Blog Posts Using Guided-topic Model

: Organizations are plagued by sophisticated and diversiﬁed cyber attacks. In order to prevent such attacks, it is necessary to understand threat trends and to take measures to protect their assets. Security vendors publish reports which contain threat trends or analysis of malware. These reports are useful for help in responding to a cyber security incident. However, it is di ﬃ cult to collect threat information from multiple sources such as security blog posts. In this paper, we propose a method to e ﬃ ciently collect information from the relationship between words using SeededLDA. In our case studies, we visualize the relationship between the words from security blog posts which were published in 2017 by eight security vendors, and demonstrate how our method helps to understand threat trends in the IoT industry and ﬁnancial institutions.
Construction of mutually unbiased maximally entangled bases in C2s ⊗ C2s by using Galois rings

Mutually unbiased bases plays a central role in quantum mechanics and quantum information processing. As an important class of mutually unbiased bases, mutually unbiased maximally entangled bases (MUMEBs) in bipartite systems have attracted much attention in recent years. In the paper, we try to construct MUMEBs in C 2 s ⊗ C 2 s by using Galois rings, which is different from the work in [17], where ﬁnite ﬁelds are used. As applications, we obtain several new types of MUMEBs in C 2 s ⊗ C 2 s and prove that M ( 2 s , 2 s ) ≥ 3 ( 2 s − 1 ) , which raises the lower bound of M ( 2 s , 2 s ) given in [16].
Distribution of dental schools in Brazil, 2015

Introduction: The geographical distribution of dentistry schools has been the object of study in Brazil and in other parts of the world. Aim: To analyze the distribution of dentistry schools in Brazil by states and to correlate with the number of dentists in 2015. Methods: This is a cross-sectional study. The analysis of the courses distribution was carried out by states and categorized by public or private schools. All the institutions′ addresses were geocoded and mapped to illustrate the spatial distribution of dental courses. To determine the association between the number of faculties by state and the number of dentists, the Spearman correlation test was applied with the level of decision (alpha = 0.05) for correlating the variables. Results: The distribution of schools and dentists were irregular. In 2015, there were 232 dental courses in operation; being 56 (24%) public and 176 (76%) private in Brazil, and all 26 states and the Federal District have dental courses. The Spearman test showed a strong positive correlation between the number of dental schools and the number of dentists. Conclusion: The distribution of dental schools has reflexes in the distribution of health professionals.
Three essays in health economics : determinants of individual health, medical care use, and treatment

This dissertation studies and identifies determinants of individual health. The first chapter analyzes how the supply of medical care affects patient treatment and health outcomes, focusing on how hospitals respond to the loss of a profitable service line. This chapter provides strong evidence that hospital spillovers across service lines are empirically important and that hospitals differentiate treatment by patient payer type. Hospitals practice both revenue augmenting and cost-cutting behavior in other lines of care, targeting specific procedures and payers according to their profitability. Specifically, they increase the number of surgical procedures and perform more marginal surgeries. The effects are concentrated in medical specialties where there are more discretionary surgeries and higher profit margins. Furthermore, hospitals cut back on unprofitable treatment by reducing non-elective admissions and uninsured elective care. Hospitals also increase the intensity of treatment among private payers. The second chapter of this dissertation investigates the demand side of health care, analyzing the role that health insurance plays on primary medical care usage by young American adults. I find office-based physician visits and prescription drugs are not affected by insurance, but dental visits are. There is a small increase in out-of-pocket expenditures caused by insurance loss, concentrated heavily at the top of the distribution. No change in health status or ability to afford care is found. The findings shed light on the expected welfare benefits of recent US health care policies targeting young adults. The final chapter of this dissertation analyzes the extent to which the early childhood environment shapes child health and development outcomes and, specifically, whether universal childcare levels the playing field across children. I analyze the introduction of a universal childcare program in Quebec in 1997, testing its impact on the distribution of child health and development outcomes. I find that there is little heterogeneity in the response to the policy across the distributions of child motor skills and cognitive outcomes. I do, however, find evidence that it led to a reduction in child body weight at the upper end of the distribution.
A Study Improving a Nurse's Walking Path and Staff Visibility in General Hospital Wards

The purpose of this study is to suggest ways to improve a staff's working environment, mainly focusing on shortening the walking distance of nurses and enhancing staff visibility to patients from the nurse station (NS). Article reviews were performed on nurses' walking distance and staff visibility. Seven general hospital wards with different characteristics in layouts have been chosen and analyzed, four wards for nurses' walking paths and six wards for staff visibility. Interviews with nurses and drawing reviews were performed to figure out their care delivery method and the relevance it has to the layouts. Furthermore, the quantitative data collected by drawing reviews were compared among wards. The result of this study is as follows. Nurses walked longer distances where nurses' designated rooms were not pertinent to the ward's layout. The standard deviation of nurses' walking distance in a ward differed by the location of the NS and the arrangement of patient room types. Staff visibility was better in the ward that had a double corridor type, centrally located NS and shared rooms near the NS. To sum up, the nursing path and staff visibility from the NS were affected by a combination of the ward's plan, rooms' layouts, corridor type, nurse station type and the operating systems of wards. This study focuses on improving staff and nurses' working environment, which are easily neglected due to patients being the first priority in hospital design. Thus, this work highlights the importance of understanding an operating system, objectives and the priority of wards in planning it. It will help designers and planners to provide better environments for employees.
Geomaterials (Mineralogy) Geochemical and microbiological controls on dissimilatory iron reduction

Recent experimental studies permit development of conceptual and quantitative models of microbial Fe(III) oxide reduction at circumneutral pH that can be compared to and contrasted with established models of abiotic mineral dissolution. The findings collectively support a model for controls on enzymatic reduction that differs fundamentally from those applied to abiotic reductive dissolution as a result of two basic phenomena: (1) the relatively minor influence of oxide mineralogical and thermodynamic properties on rates of enzymatic reduction compared to abiotic reductive dissolution, and (2) the major limitation which sorption and/or surface precipitation of biogenic Fe(II) on residual oxide and Fe(III)-reducing bacterial cell surfaces poses to enzymatic electron transfer in the presence of excess electron donor. Parallel studies with two well-characterized Fe(III)-reducing organisms (Shewanella putrefaciens and Geobacter sulfurreducens) lead to common conclusions regarding the importance of these phenomena in regulating the rate and long-term extent of Fe(III) oxide reduction. Models in which rates of enzymatic reduction are limited by Fe(III)-reducing bacterial cell density together with the abundance of ‘available’ oxide surface sites (as controlled by oxide surface area and the accumulation of surface-bound biogenic Fe(II)) provide an adequate macroscopic description of controls on the initial
Comparison of the effect of cholecalciferol and 25-hydroxycholecal- ciferol on the characteristic features of femoral and tibia bones in male fattening turkeys Vergleich der Wirkung von Cholecalciferol und 25-Hydroxy-Cholecalciferol auf Knochen- merkmale von Femur und Tibia bei männlichen Mastputen

Disorders of leg bones and ossification processes as well as other metabolic disorders are often observed in heavy-type turkeys growing fast to around 22 weeks of age, including on Polish farms (HESTER, 1994; HOCKING and WHITEHEAD, 1992; MAZURKIEWICZ, 2005). Such abnormalities may result from the deficiency or poor absorption of vitamin D3. Complete turkey diets are supplemented with synthetic vitamin D3 (cholecalciferol) in quantities determined by the birds' age. It is believed that the optimal dose of cholecalciferol is 100 μ/kg – 62.5 μg/kg of feed (PAN, 2005). Cholecalciferol manifests its biological activity only when converted to the active metabolite 25-hydroxycholecalciferol (25-OH-D3). This conversion takes place as a result of several complex biochemical reactions which render the process relatively ineffective (KUTNER, 1993). The success of research efforts to produce 25-hydroxycholecalciferol by industrial synthesis paved the way to its application in animal feed. When administered to birds, this form of vitamin D3 does not impair liver functions because it is not subject to the hydroxylation process (HEALY et al., 2003; PANDA et al., 2001). The objective of this study was to determine, for the first time, the effect of the replacement of vitamin D3 with its hydroxyl derivative 25-OH-D3 in diets fed to turkeys on selected qualitative attributes of femoral and tibia bones.
Addictive Behaviors and Chronic Pain in a High-Risk Population

In this study, we use a cross-sectional design to examine the relationship between addictive behaviors and self-reported pain in a high-risk population of driving under the influence (DUI) violators. Our results suggest that individuals identified as having potentially dependent relationships with food, nicotine, drugs, alcohol, and sex have a greater likelihood of experiencing pain. However, the magnitude of the association varied significantly among the addictive domains and in relation to the severity and body location of the reported pain. Our results demonstrate simple and additive effects associated with the confounding relationships between multiple addictions and the likelihood of experiencing chronic pain. Potential explanations for these relationships range from the physiological relationship between obesity and lower body joint strain to potential psychological relationships associated with sex addiction and the experience of pain. Overall, the results highlight statistically important relationships between addiction, multiple addictions, and the experience of chronic pain.
Badania kontrolne po leczeniu w najczęstszych nowotworach litych

Surveillance after oncological treatment constitutes a necessary element of comprehensive cancer care. Determining optimal follow-up schedules, including their cost effectiveness, is critical on clinical, organisational and economic grounds. Owing to a lack of prospective clinical studies providing the highest level of evidence, in most cancers optimal surveillance schemes cannot be determined. Hence, currently most recommendations are based on retrospective studies and expert opinions. In Poland comprehensive and uniform recommendations on post-treatment surveillance in cancer patients are not available. This article, prepared by a group of experts in oncology and family medicine, presents a proposal for the follow-up schemes after treatment in major solid
Eccentric Exercise and Delayed Onset of Muscle Soreness (DOMS) – an Overview

Abstract Aim: The aim of this literature based analysis was to identify the reasons, kinetics and intervention possibilities of delayed onset of muscle soreness (DOMS). Material and Methods: Literature analysis via common online search engines PubMed and MedLine supported by a clinical study with multiple evaluation points (before exercise, at 12, 13, 14, 16, 20 and 24 h after exercise and subsequently in 12 h intervals up to 156 h post exercise) to investigate pain kinetics. The study investigated the effect of walking down stairs with a total altitude of 300–400 m depending on body weight on muscle pain in 48 healthy subjects. Subjects rated pain on a 10 point categorical Likert scale. Outcome and Discussion: DOMS is almost exclusively caused by eccentric muscle contractions. The pain starts after 6–8 h and peak between 24–48 h after the exercise and can stay up to one week. There are numerous treatment methods for DOMS such as: medical, nutritional and physical interventions. Several methods were found to alleviate DOMS and/or to reduce the inflammation parameters, unfortunately, most of them only after 24–48 h. But the results for most approaches are still controversial. Use of non-steroidal anti-inflammatory drugs might initially reduce pain but on the expense of even a delay in recovery. Conclusion: Many treatment options were found that reduced inflammation and pain significantly. However, none of these treatments were found consistently to support or accelerate the structural and functional muscle regeneration. Regular physical training to condition the muscles to unfamiliar eccentric exercise appears to be the best preventive approach. Additional eccentric training during rehabilitation is beneficial for patients with reduced cardio-pulmonary capacity.
PWE-282 The role of α-fetoprotein in hepatocellular carcinoma surveillance

Introduction The most efficient and cost-effective programme for HCC surveillance is the subject of ongoing debate. Current UK standard practice for HCC surveillance in high risk populations consists of 6 monthly ultrasound (US) and α-fetoprotein (AFP) measurement. However, the most recent international guidelines on HCC surveillance (AASLD) state that US alone is the most appropriate means of HCC surveillance.1 2 To investigate the relative contributions of US and AFP to HCC surveillance we have performed a retrospective analysis of the records of consecutive cases of newly diagnosed HCC within two patient cohorts. Methods We retrospectively reviewed the electronic records of: (1) All 78 patients diagnosed with HCC in NHS Lothian between 1 January 2010 and 30 September 2011. (2) All 46 patients referred to the Scottish Liver Transplant Unit (SLTU) with HCC for liver transplant assessment from 1 January 2010 to 31 August 2011. Demographic details, mode of HCC detection and patient outcomes were recorded. Patients were identified as undergoing HCC surveillance if they were having 6 monthly US and AFP measurements. An elevated AFP was defined as >6 kU/l. Results 36% (28/78) of the patients diagnosed with HCC in NHS Lothian were diagnosed through HCC surveillance. Of these 28 patients 39% (11/28) had the suspicion of HCC raised by AFP alone, 32% (9/28) were detected by both AFP and US and only 25% (7/28) were detected by US alone. 1 HCC was detected by CT scan. The overall sensitivity of AFP for detecting HCC in the surveillance group was 71% (20/28). 84% (36/43) of the SLTU cohort were diagnosed through regular HCC surveillance. 33% (12/36) by AFP alone, 25% (9/36) by US alone and 42% (15/36) by both AFP and US. 69% (25/36) had a raised AFP at HCC diagnosis. 76% (19/25) of patients with a raised AFP at diagnosis were offered potentially curative treatment. Conclusion In conclusion our data does not support the current AASLD guidelines stating US alone should be used for HCC surveillance. In both patient cohorts over a third of HCC cases detected through surveillance were identified by a rising AFP alone. Our results indicate AFP is therefore an important and effective addition to US. Additional refinement of how AFP levels are interpreted, in particular progressive rises in AFP, may enable increased sensitivity and specificity and further improve the efficacy of HCC surveillance. Competing interests None declared. References 1. Bruix J, Sherman M. Management of Hepatocellular Carcinoma: An Update. 2010. http://www.aasld. org/practiceguidelines/ (accessed Feb 2011). 2. Marrero Jorge A, El-Serag Hashem B. Alpha-fetoprotein should be included in the hepatocellular carcinoma surveillance guidelines of the american association for the study of liver diseases. Hepatology 2011;53:1060–1.
Don’t forget about the pancreas! Useful tips on ultrasound

Transabdominal ultrasound (TAUS) remains the most widely available, non-invasive and least expensive initial imaging modality of the pancreas. Awareness of a range of pancreatic pathology is imperative when determining the need for further cross-sectional imaging or increasingly, endoscopic ultrasound (EUS). Given the spectrum of pathologic processes that affect the pancreas, alongside the significant overlap in clinical presentation, the major task on the initial TAUS is to distinguish normal from abnormal and subsequently inflammatory-related pathology from underlying neoplasia. This article aims to present useful sonographic signs that demonstrate and differentiate pancreatic pathologies. These useful sonographic signs are highlighted through a series of benign and neoplastic conditions involving the pancreas and correlation is made with alternative imaging including computed tomography (CT), magnetic resonance imaging (MRI) and EUS. In conclusion, TAUS continues to have a useful role in the initial assessment of the pancreas. Recognising useful sonographic signs, as well as their limitations, is important in the avoidance of misdiagnosis and accurately triaging patients with regard to further appropriate imaging investigations.
2-(4-Bromo­phenyl)-5-methyl-2,3-di­hydro-4H-1,2,4-triazol-3-one

In the title compound, C9H8BrN3O, the dihedral angle between the phenyl and triazole rings is 8.93 (14)°. In the crystal, the mol­ecules exist as centrosymmetrically related N—H⋯O hydrogen-bonded dimers.