jimnoneill/paper-to-field-training huggingface dataset:
Safety, pharmacokinetics, and pharmacodynamics of oral omaveloxolone (RTA 408), a synthetic triterpenoid, in a first-in-human trial of patients with advanced solid tumors

Field: Medicine (Health Sciences)

Ben C Creelan,1 Dmitry I Gabrilovich,2 Jhanelle E Gray,1 Charles C Williams,1 Tawee Tanvetyanon,1 Eric B Haura,1 Jeffrey S Weber,3 Geoffrey T Gibney,4 Joseph Markowitz,5 Joel W Proksch,6 Scott A Reisman,6 Mark D McKee,7 Melanie P Chin,6 Colin J Meyer,6 Scott J Antonia11Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Magnolia Drive, Tampa, FL, USA; 2The Wistar Institute, Philadelphia, PA, USA; 3Laura and Isaac Perlmutter Cancer Center, New York, NY, USA; 4Department of Medicine, Georgetown-Lombardi Comprehensive Cancer Center, Washington, DC, USA; 5Department of Cutaneous Oncology, H. Lee Moffitt Cancer Center and Research Institute, Magnolia Drive, Tampa, FL, USA; 6Reata Pharmaceuticals, Inc., Irving, TX, USA; 7AbbVie, Inc., North Chicago, IL, USABackground: Omaveloxolone is a semisynthetic oleanane triterpenoid that potently activates Nrf2 with subsequent antioxidant function. We&nbsp;conducted a first-in-human Phase I clinical trial (NCT02029729) with the primary objectives to determine the appropriate dose for Phase II studies, characterize pharmacokinetic and pharmacodynamic parameters, and assess antitumor activity.Methods: Omaveloxolone was administered orally once daily continuously in a 28-day cycle for patients with stage 4 relapsed/refractory melanoma or non-small cell lung cancer. An accelerated titration design was employed until a grade 2-related adverse event (AE) occurred. A standard 3+3 dose escalation was employed. Single-dose and steady-state plasma pharmacokinetics of the drug were characterized. Downstream Nrf2 activation was assessed in peripheral blood mononuclear cells by quantification of target gene mRNA expression.Results: Omaveloxolone was tested at four dose levels up to 15 mg given orally once daily. No dose-limiting toxicities were detected, and the maximum tolerated dose was not determined. All drug-related AEs were either grade 1 or 2 in severity, and none required clinical action. The most common drug-related AEs were elevated alkaline phosphatase (18%) and anemia (18%). No drug interruptions or reductions were required. Omaveloxolone was rapidly absorbed and exhibited proportional increases in exposure across dose levels. With some exceptions, an overall trend toward time-dependent and dose-dependent activation of Nrf2 antioxidant genes was observed. No confirmed radiologic responses were seen, although one lung cancer subject did have stable disease exceeding 1 year.Conclusions: Omaveloxolone has favorable tolerability at biologically active doses, although this trial had a small sample size which limits definitive conclusions. These findings support further investigation of omaveloxolone in cancer.Keywords: antioxidant inflammation modulator, nitrotyrosine, nitric oxide synthase, melanoma, non-small cell lung cancer, immuno-oncology, myeloid-derived suppressor cells, bardoxolone methyl
Bilateral Thalamic Infarction by Percheron Artery Occlusion

Field: Medicine (Health Sciences)

Objective: The artery of Percheron is an uncommon single trunk variant of the thalamoperforating arteries that supplies the paramedian thalamic territory bilaterally and the rostral midbrain. Four cases of artery of Percheron (PA) occlusion with bilateral paramedian thalamic infarctions are reported, considering aspects of its clinical and radiological presentation, as well its prognosis. Methods: Four patients with infarcts due to PA occlusion were diagnosed. The data for the study were retrospectively obtained from the medical records of patients. Results: Four patients with PA infarctions were diagnosed. All patients have presented a symmetrical bilateral paramedian thalamus infarction, and two of them also presented midbrain involvement, with abnormal images on MRi and CTs. Clinical presentations have included sudden onset of bilateral palpebral ptosis, headache, ophthalmoplegia, aphasia, prostration, confabulation, mental confusion and ataxia. Conclusion: Although rare, occlusion of artery of Percheron should be part of the differential diagnosis when symmetrical bilateral paramedian thalamic and mesencephalic lesions occur
Intraspecies allometric equations derived using phase 1 clinical adult pharmacokinetic parameters for pediatric dosing of lamivudine, nevirapine, and zidovudine

Field: Pharmacology, Toxicology and Pharmaceutics (Life Sciences)

Adverse drug reactions causing treatment change among patients taking highly active antiretroviral therapy in health care facilities of Mekelle, EthiopiaAbebe Ejigu, Mussie Gehzu, Werissaw Haileselassie
Evaluation of urea-nitrate supplement made with Maillard reaction for delaying ruminal ammonia formation

Field: Agricultural and Biological Sciences (Life Sciences)

Ruminants have a stomach that can convert NPN compounds as amino acids. This ability has not been effectively utilised. The present study aimed to determine the influence of urea-nitrate supplementation on rumen fermentation profiles in vitro . The urea-nitrate was prepared by employing the Maillard reaction (MR) using two different sugar sources, i.e., molasses and liquid waste of palm juice. The present study's randomized complete block design consisted of five treatments and four replications. The treatments are T0 = control diet; T1 = T0 + urea; T2 = T0 + urea-nitrate; T3 = T0 + urea-nitrate MR with molasses; T4 = T0 + urea-nitrate MR with liquid waste of palm juice, where urea and urea-nitrate supplementation treatments were expected to enhance dietary crude protein by 2% of the control diet. Results revealed that T3 treatments enhanced ammonia concentration up to 11.4% compared to T0, T1, and T4 (P<0.05). However, treatments were similar in terms of rumen pH, volatile fatty acids, microbial protein synthesis, total gas production, methane production, dry matter digestibility, and organic matter digestibility. In conclusion, the slow release urea-nitrate supplementation in ruminant feed may inhibits ammonia formation in the rumen in vitro.
The study of drug interaction on pneumonia patients at RSUP Dr. M. Djamil Padang

Field: Pharmacology, Toxicology and Pharmaceutics (Life Sciences)

Abstract Background: Pneumonia is one of the diseases that cause high rates of toddler deaths in the world. In Indonesia, pneumonia is the second cause of death of infants and toddlers after diarrheal diseases. Most pneumonia patients are treated with other diseases so many pneumonia patients receive more than two types of drugs in one prescription, this has the potential for drug interactions with drugs. Objective: The aim of this study was to look at potential occurrences of drug interactions in toddler patients at Dr.M. Djamil Padang Hospital hospitalized in 2019. Methods: This research was nonexperimental research design with cross-sectional descriptive methods of analysis and the data retrieved retrospectively. The patient's medical records were analyzed using the Drugs.com software and Medscape. Results: There were 62 patients who met the inclusion criteria. Among them, there were 5 pneumonia patients (8.1%) who experienced drug interactions with drugs, with the pharmacokinetic category as many as 3 cases (42.9%) affecting metabolism and drug interactions in the pharmacodynamic category by 4 cases (57.1%). Based on the severity of drug interactions, this study found 1 minor case (14.3%), 5 moderate cases (71.4%), and 1 major case (14.3%). Conclusion: From the results of the study it can be concluded that there was a potential for drug interactions in pneumonia toddler patients at Dr.M. Djamil Padang Hospital in the period 2019. Keywords: Bronchopneumonia, drug Interactions, toddler
Pipeline Embolization Device for intracranial aneurysms in a large Chinese cohort: factors related to aneurysm occlusion

Field: Medicine (Health Sciences)

Background and Purpose: The Pipeline Embolization Device (PED, Covidien/Medtronic) is widely used to treat intracranial aneurysms. This PED in China post-market multi-center registry study (PLUS) investigated safety and effectiveness of the PED for intracranial aneurysms in the Chinese population. Methods: This was a panoramic, consecutive, real-world cohort registry study. Patients treated with PED with or without coils between November 2014 and October 2019 at 14 centers in China were included, and those treated by parent vessel occlusion or other stents were excluded. Study outcomes included angiographic evaluation of aneurysm occlusion, complications, in-stent stenosis, and predictors of aneurysm occlusion. A central committee reviewed all imaging and endpoint events. Results: In total, 1171 patients with 1322 intracranial aneurysms were included. The total occlusion rate was 81.4% (787/967) at mean follow-up of 8.96 ± 7.50 months, with 77.1% (380/493) occlusion in the PED alone and 85.9% (407/474) in the PED plus coiling group. On multi-variate analysis, female sex, hyperlipidemia, vertebral aneurysms, PED plus coiling, and blood flow detained to venous phase were significant predictors of aneurysm occlusion. In posterior circulation cohort, there was no variable associated with aneurysm occlusion. In-stent stenosis predictors included current smoking and cerebral sclerosis/stenosis. Conclusion: In the largest series on PED of multi-center date of China, data suggest that treatment with the flow-diverting PED in intracranial aneurysms was efficacious. The treatment of PED combined coiling and blood flow detained to venous phase after PED implant were associated with aneurysmal occlusion. The occlusion rate of vertebral aneurysms was higher than other location aneurysms. Clinical Trial Registration: ClinicalTrials.gov identifier: NCT03831672.
Internet of Things and Blockchain

Field: Computer Science (Physical Sciences)

The idea of the Internet of Things (IoT) is fascinating and energizing, however the most testing part of IoT is the safe condition that associates all the structure squares of IoT-engineering. The blockchain is a database that keeps up constant information records. It is dispersed normally, implying that the ace PC isn't liable for the whole arrangement. Rather, the taking an interest hubs have a chain duplicate. It is continually developing—information records are just remembered for arrangement. Blockchain innovation is a lost connects to settling protection issues and depending on the Internet of Things. Blockchain modernization might be the silver covering for the IoT business. It may be utilized well to follow billions of connected gadgets that empower exchange management and correspondence between gadgets that permit significant investment funds for IoT mechanical engineers. This problematic methodology stays away from dissatisfaction, building a progressively amicable organic method for working gadgets. This part depicts the historical backdrop of IoT, genuine examinations utilizing IoT gadgets in the present and future world, different kinds of sensors and actuators, mix of blockchain and IoT, edge registering and blockchain are isolated into 6 areas.
Trade Preferences for Developing Countries

Field: Economics, Econometrics and Finance (Social Sciences)

This report draws on a body of existing literature to assess the impact of trade preferences granted by the European Union on trade and welfare in developing countries. It is argued that the Everything But Arms amendment to the EU preference scheme will have limited effect on export potential and welfare in the least developed countries (LDCs). The EU would do well to simplify compliance with their rules of origin. When LDCs are granted deeper preferences under continued domestic agricultural policies in the EU, US, Canada and Japan, resources in LDCs will move towards the agricultural sector. The expected effect impact on LDCs of extending preferences to non-LDCs is quite small, while the negative effect of reductions of MFN tariffs under trade liberalisation is stronger.
Real-Time Indoor Object SLAM with LLM-Enhanced Priors

Field: Computer Science (Physical Sciences)

Object-level Simultaneous Localization and Mapping (SLAM), which incorporates semantic information for high-level scene understanding, faces challenges of under-constrained optimization due to sparse observations. Prior work has introduced additional constraints using commonsense knowledge, but obtaining such priors has traditionally been labor-intensive and lacks generalizability across diverse object categories. We address this limitation by leveraging large language models (LLMs) to provide commonsense knowledge of object geometric attributes, specifically size and orientation, as prior factors in a graph-based SLAM framework. These priors are particularly beneficial during the initial phase when object observations are limited. We implement a complete pipeline integrating these priors, achieving robust data association on sparse object-level features and enabling real-time object SLAM. Our system, evaluated on the TUM RGB-D and 3RScan datasets, improves mapping accuracy by 36.8\% over the latest baseline. Additionally, we present real-world experiments in the supplementary video, demonstrating its real-time performance.
Differences in Serum Magnesium Levels in Diabetic and Non-Diabetic Patients Following One-Anastomosis Gastric Bypass

Field: Medicine (Health Sciences)

Patients with obesity and type 2 diabetes mellitus (T2DM) are regarded to have reduced serum magnesium (Mg) concentrations. We aimed to assess the changes in serum Mg concentrations at 12-month follow-up in patients, with and without T2DM, who underwent one anastomosis gastric bypass surgery. Overall, 50 patients (80% female, age 42.2 (12.5) years) with morbid obesity (mean baseline BMI 43.8 (4.3) kg/m2) were included in the analysis. Half of the included patients had T2DM diagnosed at baseline, and these patients showed lower serum Mg concentration (0.78 (0.07)) vs. 0.83 (0.05) mmol/L; p = 0.006), higher blood glucose levels (129.9 (41.3) vs. 87.6 (8.1) mg/dL; p < 0.001) as well as HbA1c concentrations (6.7 (1.4) vs. 5.3 (0.5)%; p < 0.001). During follow-up, BMI and glucose levels showed a decrease; however, serum Mg levels remained stable. At baseline 42% of patients were found to be Mg deficient, which was reduced to 33% at six months and to 30% at 12 months follow-up. Moreover, patients with T2DM had an odds ratio of 9.5 (95% CI = 3.0–29.7; p < 0.001) for magnesium deficiency when compared to patients without T2DM. Further research into the role of Mg and its role in T2DM and other obesity-related comorbidities are needed.
Introduction of a new process with learning about installation and operation

Field: Decision Sciences (Social Sciences)

Abstract A model is formulated and solved to investigate the optimal introduction of a new production process when the unit cost of the old process increases with cumulative output and the new process is subject to two learning curves. Capital costs of the new process come down with cumulative experience of installation of new capacity, and operating costs are reduced as operating experience accumulates. Demand is assumed to be constant. Because of an upper limit on the rate of expansion of capacity, conversion to the new process takes place gradually over an interval. It is shown that an equivalent, constant capital cost of the new process may be calculated before solving the model; the same may be done for the operating cost in some cases. An example with oil from the Canadian tar sands as the new process is solved, and extensions to the model are discussed.
Global Analysis of TDP-43 Interacting Proteins Reveals Strong Association with RNA Splicing and Translation Machinery

Field: Biochemistry, Genetics and Molecular Biology (Life Sciences)

TDP-43 is a highly conserved and ubiquitously expressed member of the heterogeneous nuclear ribonucleoprotein (hnRNP) family of proteins. Recently, TDP-43 was shown to be a major disease protein in the ubiquitinated inclusions characteristic of most cases of amyotrophic lateral sclerosis (ALS), <i>tau</i>-negative frontotemporal lobar degeneration (FTLD), and inclusion body myopathy. In these diseases, TDP-43 is redistributed from its predominantly nuclear location to ubiquitin-positive, cytoplasmic foci. The extent to which TDP-43 drives pathophysiology is unknown, but the identification of mutations in TDP-43 in familial forms of ALS and FTLD-U suggests an important role for this protein in pathogenesis. Little is known about TDP-43 function and only a few TDP-43 interacting proteins have been previously identified, which makes further insight into both the normal and pathological functions of TDP-43 difficult. Here we show, via a global proteomic approach, that TDP-43 has extensive interaction with proteins that regulate RNA metabolism. Some interactions with TDP-43 were found to be dependent on RNA-binding, whereas other interactions are RNA-independent. Disease-causing mutations in TDP-43 (A315T and M337V) do not alter its interaction profile. TDP-43 interacting proteins largely cluster into two distinct interaction networks, a nuclear/splicing cluster and a cytoplasmic/translation cluster, strongly suggesting that TDP-43 has multiple roles in RNA metabolism and functions in both the nucleus and the cytoplasm. Finally, we found numerous TDP-43 interactors that are known components of stress granules, and indeed, we find that TDP-43 is also recruited to stress granules.
The Relationship Between Sleep Disturbance, Suicidal Ideation, Suicide Attempts, and Suicide Among Adults: A Systematic Review

Field: Medicine (Health Sciences)

Suicide is a significant global health concern; identification of modifiable risk factors can guide future research and prevention efforts. A systematic literature review was undertaken to summarize whether disrupted sleep, which has garnered increased attention as a risk factor for suicidal thoughts and behaviors, has continued to be associated with suicide in recent years. The search resulted in 1,806 abstracts with 188 identified for full text review. Limiting studies to 2012–2015 publications with adult participants and an interpretable relationship between sleep and suicide outcomes left 36 articles for the review. Five new articles focused on suicide decedents, eight on veteran/military populations, but relatively few were longitudinal studies ( n = 4) and none assessed sleep apnea. A majority of studies used statistical methods to control for psychopathology, strengthening the overall finding that recent work lends further support for disrupted sleep as an important risk factor, and potential warning sign, for suicide. [ Psychiatr Ann . 2016;46(3):177–186.]
Work and Experience from a Phenomenological Approach

Field: Social Sciences (Social Sciences)

The article presents a phenomenological approach to the analysis of work experience from the notion of context of meaning and context of experience in finite areas of meaning in the work of Alfred Schütz. From this approach, a three-dimensional analysis of the world of work (Wirkwelt) is proposed, where work is simultaneously considered as a structure, as a social action and as an intersubjective environment. With this, it is sought to deepen a better understanding of the heterogeneous phenomena of the world of work.
Agrobacterium tumefaciens mediated transient expression of plant cell wall‐degrading enzymes in detached sunflower leaves

Field: Agricultural and Biological Sciences (Life Sciences)

For biofuel applications, synthetic endoglucanase E1 and xylanase (Xyn10A) derived from Acidothermus cellulolyticus were transiently expressed in detached whole sunflower (Helianthus annuus L.) leaves using vacuum infiltration. Three different expression systems were tested, including the constitutive CaMV 35S‐driven, CMVar (Cucumber mosaic virus advanced replicating), and TRBO (Tobacco mosaic virus RNA‐Based Overexpression Vector) systems. For 6‐day leaf incubations, codon‐optimized E1 and xylanase driven by the CaMV 35S promoter were successfully expressed in sunflower leaves. The two viral expression vectors, CMVar and TRBO, were not successful although we found high expression in Nicotiana benthamiana leaves previously for other recombinant proteins. To further enhance transient expression, we demonstrated two novel methods: using the plant hormone methyl jasmonic acid in the agroinfiltration buffer and two‐phase optimization of the leaf incubation temperature. When methyl jasmonic acid was added to Agrobacterium tumefaciens cell suspensions and infiltrated into plant leaves, the functional enzyme production increased 4.6‐fold. Production also increased up to 4.2‐fold when the leaf incubation temperature was elevated above the typical temperature, 20°C, to 30°C in the late incubation phase, presumably due to enhanced rate of protein synthesis in plant cells. Finally, we demonstrated co‐expression of E1 and xylanase in detached sunflower leaves. To our knowledge, this is the first report of (co)expression of heterologous plant cell wall‐degrading enzymes in sunflower. © 2014 American Institute of Chemical Engineers Biotechnol. Prog ., 30:905–915, 2014
Exploring the nexus between sectoral stock market fluctuations and macroeconomics changes before and during the COVID-19 pandemic

Field: Economics, Econometrics and Finance (Social Sciences)

Investors may find it challenging to invest due to economic fluctuations during COVID-19. This study aims to examine the relationship between economic fluctuations and the Indonesian sectoral stock market in the consumer goods sector (CGI), basic industrial and chemical sector (BIC), and miscellaneous industry (MSI), both before and during the COVID-19 pandemic in Indonesia. The monthly time-series data used in the empirical approach cover the period from January 2008 to December 2020. The analysis used forecast error variance decomposition, vector autoregression, impulse response function analysis, and causality investigation. The econometric results showed that previous period shocks in each industrial sector stock market had a disadvantageous effect on future stock market earnings. Additionally, while the CGI stock market positively affects the Rupiah exchange rate, the MSI industrial sector is negatively impacted by inflationary pressures. Also connected to the MSI stock market are fluctuations in inflation. Conversely, the exchange rate affects MSI and CGI. Furthermore, for the CGI and BIC stock markets, a one-way causation relationship is observed. Another notable result was that all three industrial sectors responded positively when inflation and exchange rates were disrupted. It implies that, for convenience, investors will seek out other areas of the stock market. Therefore, a quick government response is needed to handle the economy during economic fluctuations accompanied by the COVID-19 pandemic so that it does not have an impact on the future.
Photolysis of t-butyl-p-quinones: competing 1,4- and 1,5-dipolar cycloadditions of the photoproduct to nitriles and ketones

Field: Chemistry (Physical Sciences)

Spirocyclopropyl ketones (XIV), obtained from the photolysis of t-butyl-p-quinones (I;R1= H or But), rearrange to (III) and (IV) and add nitriles and ketones in competitive 1,4- and 1,5-dipolar cycloadditions giving 6- and 7-membered heterocyclic compounds (VII)–(XII).