jimnoneill/paper-to-field-training huggingface dataset:
Zinc adaptation and resistance to cadmium toxicity in mammalian cells. Molecular insight by proteomic analysis

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

To identify proteins involved in cellular adaptive responses to zinc, a comparative proteome analysis between a previously developed high zinc- and cadmium- resistant human epithelial cell line (HZR) and the parental HeLa cells has been carried out. Differentially produced proteins included co-chaperones, proteins associated with oxido-reductase activities, and ubiquitin. Biochemical pathways to which these proteins belong were probed for their involvement in the resistance of both cell lines against cadmium toxicity. Among endoplasmic reticulum stressors, thapsigargin sensitized HZR cells, but not HeLa cells, to cadmium toxicity more acutely than tunicamycin, implying that these cells heavily relied on proper intracellular calcium distribution. The similar sensitivity of both HeLa and HZR cells to inhibitors of the proteasome, such as MG-132 or lactacystin, excluded improved proteasome activity as a mechanism associated with zinc adaptation of HZR cells. The enzyme 4-hydroxyphenylpyruvate dioxygenase was overproduced in HZR cells as compared to HeLa cells. It transforms 4-hydroxyphenylpyruvate to homogentisate in the second step of tyrosine catabolism. Inhibition of 4-hydroxyphenylpyruvate dioxygenase decreased the resistance of HZR cells against cadmium, but not that of HeLa cells, suggesting that adaptation to zinc overload and increased 4-hydroxyphenylpyruvate removal are linked in HZR cells
Specificity and influence of climatic factors on the pollination of south-eastern Brazilian Sinningia

Field: Agricultural and Biological Sciences (Life Sciences)

Ornithophily is a widespread pollination syndrome that has evolved independently several times along the evolution of plants. It is reported in sixty-five plant families, including Gesneriaceae. One of the most diverse genera within gesneriads is Sinningia, which comprises species pollinated by bees, hummingbirds and bats. However, little is known about the reproduction biology of either species or on pollinator specificity in this genus. Based on investigations on flowering phenology, flower morpho-anatomy, volume and concentration of floral nectar, pollinators, and breeding system, this paper reports the reproduction and the pollinator specificity of Sinningia douglasii and Sinningia araneosa in natural areas in Brazil. Both species offer nectar as a resource and are exclusively pollinated by a single species of hermit hummingbird. Nectar is produced by glands around the ovary. Pollen is deposited between the base of the beak and the head feathers. Both species are self-compatible and pollinator-dependent. In both Sinningia species, the combination of protandry, pollinator specificity, due to long corolla tubes that exclude the visitation of short-billed hummingbirds. The presence of particular flower features influence the occurrence of pollination by specific pollen vectors, such as hermit hummingbirds, in deterrence of illegitimate visitors (i.e. territorial hummingbirds), protection against vigorous foraging, and accurate placement of pollen on legitimate pollinators. In addition, the foraging of Phaethornis on flowers of Sinningia is independent of relative humidity and air temperature, whereas the main factor influencing hummingbird visits is the luminosity.
Let’s Get Small: Miniaturizing Separations for Single-Cell Analysis

Field: Chemistry (Physical Sciences)

Direct profiling of biochemical expression within single cells provides insights into cellular processes that are lost when ensemble averages are measured across populations of cells. Advanced separations coupled with mass spectrometry (MS) can now quantify more than 1000 proteins within single cells. Further miniaturization of separations will greatly extend the reach of single-cell proteomics, metabolomics, and lipidomics, but key challenges in instrumentation, column technology, and ionization sources must be addressed.
Pyrophosphat-abhängige ᴅ-Fructose-6-phosphat Phosphotransferase in Rhodospirillaceae / Pyrophosphate-Dependent ᴅ-Fructose-6-phosphate-Phosphotransferase in Rhodospirillaceae

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

Abstract A pyrophosphate-dependent fructose-6 -phosphate phosphotransferase from the photosynthetic bacterium Rhodospirillum rubrum was partially purified and characterized in respect to kinetic and regulatory properties. The enzyme had a molecular weight of about 95 000 dalton and required Mg 2+ -ions for catalysis and maintenance of activity. The phosphotransferase was specific for fructose-6 -phosphate (F-6 -P) and inorganic pyrophosphate (PP) as substrates of the fructose-1,6 -bisphosphate-forming reaction (forward reaction). In the phosphate (PO-dependent back reaction, the preferred substrate was fructose-1,6-bisphosphate (FBP). At optimal pH (7.2 for the forward, and 8.6 for the back reaction) the back reaction had a slightly higher Ʋ max than the forward reaction. The substrate-saturation curves of the enzyme were all hyperbolic with intersecting kinetic pattern. The K m -values (in mᴍ) at saturating MgCl 2 -concentration were: 0.38 (F-6-P); 0.025 (PP); 0.02 (FBP) and 0.82 (P i ). The forward reaction was inhibited by ADP and AMP. The inhibition by ADP (K i = 0.18 mᴍ) was of the mixed type in respect to F-6-P, but independent of the PP-concentration. The inhibition by AMP (K i = 0.017 mᴍ) was of a more complex type, because AMP not only decreased the Ʋ max of the F-6-P-or PP-saturation curve, but also increased the Hill-coefficient from n H = 1 to n H = 2.5 of the F-6-P-saturation curve. The inhibition of the back reaction by the two adenylates was less pronounced. ATP (at 2.5 mᴍ), like citrate, inhibited the back reaction only at low MgCl 2 concentration (1 mᴍ) indicating that the inhibitory effect was due to the chela­tion of Mg 2+ . Out of 5 other species of the Rhodospirillaceae tested, the PP-dependent phospho-fructokinase was only shown to be present in Rhodopseudomonas gelatinosa.
Externalized Epidural Infusion Systems

Field: Medicine (Health Sciences)

Abstract This chapter discusses externalized epidural infusion systems in the setting of treatment of cancer pain. Indicated for a life expectancy of less than three months, external epidural infusions can provide much needed pain relief in patients with often difficult to control pain presentations. This chapter also discusses the current evidence regarding the role that neuraxial and regional analgesia plays in the reduction of cancer progression. A step-by-step procedure guideline is provided using two epidural systems, the Smith Medical port-a-cath system and the Du Pen Long-Term epidural catheter system. The differences in technique and management of the two systems are discussed.
Vote choice in the presence of targeted benefit transfers : unpacking the voter’s decision-making process

Field: Social Sciences (Social Sciences)

In many developing democracies, political campaigns distribute cash and other goods to voters prior to elections in order to mobilize support. This study examines how receiving targeted benefits from political campaigns impacts three steps in the decision-making process. Each empirical chapter in this dissertation focuses on a different step in the process and tests hypotheses with original data from the Indonesian context. The first step is acceptance: voters must overcome obstacles just to receive campaign transfers. Accordingly, Chapter Two examines the economic hurdles to obtaining targeted benefits and how these hurdles affect patterns of distribution among the voting population. It outlines a micro-economic theory that explains who accepts transfers by leveraging differences in the costs of accepting cash versus accepting in-kind transfers. Next, Chapter Three examines how targeted transfers affect voter participation in the form of turning out to vote, by those voters who do accept targeted transfers. It finds that while there is heterogeneity in how political parties mobilize voters to the polls, each strategy does increase turnout as there is no evidence of encouraging abstention among those who receive transfers. Finally, Chapter Four examines vote choice among those individuals who accepted transfers from campaigns. To test the propositions outlined in the dissertation, micro-level survey data from two typical Regency-Level elections in Indonesia are used.
Mechanism of Wettability and Pore Water Occurrence State in Overmaturity Shale: A Case Study of Longmaxi Formation Shale in South Sichuan Basin, China

Field: Earth and Planetary Sciences (Physical Sciences)

Pore water occupying pore surfaces and filling pore spaces significantly impacts the occurrence and exploration of shale gas. Shale gas exploration and development in China have shifted toward deep to ultradeep marine shale formations in the high-maturity to the overmaturity stage. However, the existing research on shale pore water mainly focuses on shallow to medium-deep shale, and the understanding of the wetting characteristics and pore water evolution of high-maturity-overmaturity marine shale is insufficient. Therefore, this study takes the Longmaxi Formation shale in the Sichuan Basin as an example to carry out contact angles, spontaneous imbibition, and drying-NMR coupling experiments to explore the wettability characteristics and pore water occurrence conditions of shale in the overmaturity stage. Subsequently, an evolution model of wettability characteristics and pore water occurrence characteristics in the overmaturity stage of shale was established. The results show that the maturity degree controls the shale wettability significantly. With increasing maturity, the Longmaxi Formation shale reservoir transforms from water-wet to weakly water-wet. The pore size range of movable water, capillary-bound water, clay-bound water, and hydration water are 6.48–8.47, 2.28–7.12, 1.07–2.28, and 1.07 nm or less, respectively. The controlling model with two stages of wettability on the occurrence of pore water was established. In stage I (R0 = 3.0%–3.8%), due to the effect of organic matter graphitization, graphitized organic matter pores collapsed under the action of ground stress. This leads to a decrease in the area available for fluid adsorption and the percentage of micropores, and the shale water-wettability is slowly weakened, so the percentage of movable water increases and then slowly decreases. In stage II (R0 = 3.8%–4.2%), with a further increase in graphitization, graphite crystals occupy the original microporous volume, resulting in a rapid weakening of shale wettability and a rapid increase in the percentage of movable water.
Role of Lu177 FAPI-09 therapy in combination with chemotherapy or immunotherapy for chemo-resistant progressive cancers: Early clinical experience.

Field: Medicine (Health Sciences)

3094 Background: Chemo resistant progressive tumours represent a major challenge in oncology. These tumours often adapt and develop resistance mechanisms that limit the efficacy of standard treatments. Lu177 FAPI-09 therapy, which targets fibroblast activation protein (FAP) expressed on cancer-associated fibroblasts (CAFs) within the tumor microenvironment, has emerged as a promising treatment option. By binding to FAP, Lu177 FAPI-09 selectively delivers radiation to the tumor stroma, potentially altering the tumor environment and making it more susceptible to subsequent therapies. This study aimed to evaluate the safety, feasibility, and effectiveness of combining Lu177 FAPI-09 therapy with chemotherapy or immunotherapy in patients with advanced chemoresistant cancers. Methods: Eighteen patients with advanced progressive and chemo resistant malignancies were included in this study. All underwent Ga-68 FAPI-09 PET/CT scans prior to treatment to confirm FAP expression in their tumors, ensuring that Lu177 FAPI-09 therapy would be beneficial. The patient group consisted of GI(7), ovarian (11). Prior to Lu177 FAPI-09 therapy, all patients had demonstrated resistance to one or more prior lines of chemotherapy or immunotherapy. Following the administration of Lu177 FAPI-09 therapy, patients received chemotherapy or immunotherapy 5 days later, tailored to their specific tumor type. Disease responses were assessed two months after the combined treatment. Results: After receiving Lu177 FAPI-09 therapy, 80% of patients showed either stable disease or a positive response to the subsequent chemotherapy or immunotherapy. The safety profile of Lu177 FAPI-09 therapy was favourable, with no major grade 3 or 4 adverse events reported. The most common side effects were mild reductions in blood counts, including neutropenia or anaemia. Overall, Lu177 FAPI-09 therapy in combination with chemotherapy or immunotherapy was well-tolerated by the majority of patients. Conclusions: Lu177 FAPI-09 therapy, when used in combination with chemotherapy or immunotherapy, shows promise in enhancing treatment responses in patients with chemo resistant progressive cancers with minimal side effects and no major toxicities. The use of Ga-68 FAPI-09 PET/CT scans to identify patients with tumors expressing FAP ensures appropriate patient selection, optimizing the likelihood of a positive outcome. These findings suggest that Lu177 FAPI-09 therapy could be an effective approach to overcome resistance and improve treatment outcomes in patients with advanced malignancies.
A low THD analog Class D Amplifier based on self-oscillating modulation with complete feedback network

Field: Engineering (Physical Sciences)

We propose a novel analog Class D Amplifier (CDA) based on self-oscillating modulation where the input of the feedback network is taken at the output of the lowpass LC filter ('complete feedback') as opposed to the prevalent (Pulse Width Modulation CDA) approach where the feedback input is taken at the output of the output stage of the CDA ('incomplete feedback'). The complete feedback approach substantially suppresses the non-linearity of the inductor of the Lowpass filter as this filter now constitutes part of the feedback loop. The proposed approach is highly hardware efficient over reported prevalent complete feedback CDAs. When the proposed complete feedback CDA is compared against the prevalent incomplete feedback approach, the proposed CDA exhibited highly suppressed THD (∼40dB relative suppression in most cases). The THD of the proposed CDA is ≤0.012% for the complete modulation index range and pertinent input signal range. Means to further reduce the THD is also suggested.
Classification of Resting State fMRI Datasets Using Dynamic Network Clusters

Field: Neuroscience (Life Sciences)

Resting state functional magnetic resonance imaging (rsfMRI) is a powerful tool for investigating intrinsic and spontaneous brain activity. The application of univariate and multivariate methods such as multi voxel pattern analysis has been instrumental in localizing neural correlates to various cognitive states and psychiatric disease. However, many existing methods of rsfMRI analysis are insufficient for investigating the true mechanism of brain activity since they make implicit assumptions that are agnostic of the temporal and spatial dynamics of brain activity. The proposed method aims to create a superior feature space for representing brain activity using k-means and to create interpretable generalizations on these features for studying group differences using support vector machine classifiers.​
Acceptability, equity, and feasibility of using antipsychotics in children and adolescents with autism spectrum disorder: a systematic review.

Field: Medicine (Health Sciences)

Abstract

Background: It is unclear whether the administration of antipsychotics to children and adolescents with autism spectrum disorders (ASD) is acceptable, equitable, and feasible. Methods: We performed a systematic review to support a multidisciplinary panel in formulating a recommendation on antipsychotics, for the development of the Italian national guidelines for the management of ASD. A comprehensive search strategy was performed to find data related to intervention acceptability, health equity, and implementation feasibility. We used quantitative data from randomized controlled trials to perform a meta-analysis assessing the acceptability and tolerability of antipsychotics, and we estimated the certainty of the effect according to the GRADE approach. We extracted data from systematic reviews, primary studies, and grey literature, and we assessed the risk of bias and methodological quality of the published studies. Results: Antipsychotics were acceptable (dropouts due to any cause: RR 0.61, 95% CI 0.48-0.78, moderate certainty of evidence) and well tolerated (dropouts due to adverse events: RR 0.99, 95% CI 0.55- 1.79, low certainty of evidence) by children and adolescents with ASD. Parents and clinicians did not raise significant issues concerning acceptability. We did not find studies reporting evidence of reduced equity for antipsychotics in disadvantaged subgroups of children and adolescents with ASD. Workloads, cost barriers, and inadequate monitoring of metabolic adverse events were indirect evidence of concerns for feasibility. Conclusion : Antipsychotics in children and adolescents with ASD were likely acceptable and possibly feasible. We did not find evidence of concern for equity.
Prospective Study of Epigenetic Age Acceleration and Incidence of Cardiovascular Disease Outcomes in the ARIC Study (Atherosclerosis Risk in Communities)

Field: Medicine (Health Sciences)

Background: DNA methylation-based patterns of biological aging, known as epigenetic age acceleration, are predictive of all-cause mortality, but little is known about their association with cardiovascular disease (CVD). Methods: We estimated 2 versions of epigenetic age acceleration (Horvath and Hannum) using whole-blood samples from 2543 blacks. Linear and Cox proportional hazards regression, respectively, were used to assess the association of age acceleration with carotid intima–media thickness (cross-sectionally) and incident cardiovascular events, including CVD mortality, myocardial infarction, fatal coronary heart disease, peripheral arterial disease, and heart failure, during a median 21-year follow-up. All models were adjusted for chronological age and traditional CVD risk factors. Results: In comparison to chronological age, the 2 measures of epigenetic age acceleration were weaker, but independent, potential risk markers for subclinical atherosclerosis and most incident cardiovascular outcomes, including fatal coronary heart disease, peripheral arterial disease, and heart failure. For example, each 5-year increment of epigenetic age acceleration was associated with an average of 0.01 mm greater carotid intima–media thickness (each P ≤0.01), and the hazard ratios (95% confidence intervals) of fatal coronary heart disease per 5-year increment in Horvath and Hannum age acceleration were 1.17 (1.02–1.33) and 1.22 (1.04–1.44), respectively. Conclusions: In this sample of blacks, increased epigenetic age acceleration in whole blood was a potential risk marker for incident fatal coronary heart disease, peripheral arterial disease, and heart failure independently of chronological age and traditional CVD risk factors. DNA methylation–based measures of biological aging may help to identify new pathophysiological mechanisms contributing to the development of CVD.
Real-world data on the efficacy and safety of apremilast in Japanese patients with plaque psoriasis

Field: Medicine (Health Sciences)

Background: Real-world data differ from clinical trial data. Although some real-world data regarding apremilast use for psoriasis treatment has been reported in Western countries, no such data has been reported in Asian countries. Objective: To study the efficacy, including Psoriasis Area and Severity Index (PASI) and drug survival, and safety of apremilast in Japanese patients with psoriasis. Methods: Data on all the patients treated with apremilast in Kurume University Hospital between May 2017 and June 2018 were retrieved, with June 30 2018, as the data lock date. Efficacy was analyzed by PASI50, PASI75, and PASI90; drug survival by Kaplan-Meier analysis; and drug safety by the proportion of adverse events (AEs). Results: Fourteen of 42 (33.3%) patients achieved PASI75/90; 16 (32%) patients had discontinued apremilast by the data lock date. Drug survival at week 28 was 70%. No serious AEs were reported; the most prevalent one was loose stools/diarrhea (60%), followed by nausea (38%). The most common reason for apremilast discontinuation was primary/secondary failure. Conclusions: Apremilast is safe and effective in Japanese patients with psoriasis. Higher occurrence of loose stools/diarrhea was noted in our cohort than that reported in Western real-world studies on apremilast.
Downregulation of miR-199b is associated with distant metastasis in colorectal cancer via activation of SIRT1 and inhibition of CREB/KISS1 signaling

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

The progression of distant metastasis cascade is a multistep and complicated process, frequently leading to a poor prognosis in cancer patients. Recently, growing evidence has indicated that deregulation of microRNAs (miRNAs) contributes to tumorigenesis and tumor progression in colorectal cancer (CRC). In the present study, by comparing the miRNA expression profiles of CRC tissues and corresponding hepatic metastasis tissues, we established the downregulation of miR-199b in CRC metastasis tissues. The decrease in miR-199b expression was significantly correlated to late TNM stage and distant metastasis. Moreover, Kaplan-Meier curves showed that CRC patients with high expression level of miR-199b had a longer median survival. Functional assays results indicated that the restoration of miR-199b considerably reduced cell invasion and migration in vitro and in vivo, and increased the sensitivity to 5-FU and oxaliplatin. Further dual-luciferase reporter gene assays revealed that SIRT1 was the direct target of miR-199b in CRC. The expression of miR-199b was inversely correlated with SIRT1 in CRC specimens. SIRT1 knockdown produced effects on biological behavior that were similar to those of miR-199b overexpression. Furthermore, through Human Tumor Metastasis PCR Array we discovered KISS1 was one of the downstream targets of SIRT1. Silencing of SIRT1 upregulated KISS1 expression by enhancing the acetylation of the transcription factor CREB. The latter was further activated via binding to the promoter of KISS1 to induce transcription. Thus, we concluded that miR-199b regulates SIRT1/CREB/KISS1 signaling pathway and might serve as a prognosis marker or a novel therapeutic target for patients with CRC.