Miracle-dz/UniFAR-FTUs huggingface dataset:
An extra copy of p53 suppresses development of spontaneous Kras-driven but not radiation-induced cancer.

The tumor suppressor p53 blocks tumor progression in multiple tumor types. Radiation-induced cancer following exposure to radiation therapy or space travel may also be regulated by p53 because p53 has been proposed to respond to DNA damage to suppress tumorigenesis. Here, we investigate the role of p53 in lung carcinogenesis and lymphomagenesis in LA-1 KrasG12D mice with wild-type p53 or an extra copy of p53 (super p53) exposed to fractionated total body irradiation with low linear energy transfer (low-LET) X-rays or high-LET iron ions and compared tumor formation in these mice with unirradiated controls. We found that an additional copy of p53 suppressed both Kras-driven lung tumor and lymphoma development in the absence of radiation. However, an additional copy of p53 did not affect lymphoma development following low- or high-LET radiation exposure and was unable to suppress radiation-induced expansion of thymocytes with mutated Kras. Moreover, radiation exposure increased lung tumor size in super p53 but not wild-type p53 mice. These results demonstrate that although p53 suppresses the development of spontaneous tumors expressing KrasG12D, in the context of exposure to ionizing radiation, an extra copy of p53 does not protect against radiation-induced lymphoma and may promote KrasG12D mutant lung cancer.
The Changes in Mean Platelet Volume after Using of Antiplatelet Drugs in Acute Ischemic Stroke: A Randomized Controlled Trial.

OBJECTIVE To measure the changes of mean platelet volume (MPV) after using four antiplatelet drugs in acute non-cardioembolic ischemic stroke patients and assess the association of antiplatelets and MPV and stroke outcome. MATERIAL AND METHOD Ischemic stroke survivors with National Institute of Health Stroke Scale (NIHSS) 8 were randomly allocated intofour groups, receiving aspirin, clopidogrel, combined aspirin and dipyridamole, and cilostazol. The change of MPV NIHSS, and modified Rankin Scale (mRS) were recorded at baseline and week 4 in all studied groups. MPV was measured using the standard automated blood test for complete blood count. RESULTS Twenty-one subjects were included in this study. They comprised of five cases in each antiplatelet group, except for aspirin, which had six subjects. Male was 57%, and hypertension was the most common risk factor (61.9%). Most of participants (76%) had small vessel disease. At 4-week, MPVwas reduced and NIHSS, mRS were improved in every studied group. Clopidogrel sign ficantly reduced NIHSS score (p = 0.003), and it produced the greatest reduction in MPV compared to others. CONCLUSION Every type of antiplatelets included in this study reduced MPV NIHSS, and mRS in acute non-cardioembolic stroke patients. Clopidogrel improved NIHSS the most.
Risk factors for preterm delivery in South Western Nigeria

This was a case–control study to determine the risk factors of preterm delivery among Nigerian women seen at Obafemi Awolowo University teaching hospital, Ile-Ife, Nigeria over a period of 9 months. All women delivering preterm were recruited into the study, with two consecutive term deliveries after each preterm delivery serving as controls. Information obtained from the women includes socio-demographic characteristics, past reproductive and present pregnancy history and outcome. Laboratory investigations were conducted as necessary. Bivariate analysis revealed 21 potential risk factors, however, following adjustment by multiple logistic regression only previous preterm delivery (OR 4.68, 2.24–6.31), previous second trimester spontaneous abortion (OR 4.48, 2.32–8.54), heavy and stressful occupation (OR 3.56, 1.05–6.45), premature rupture of fetal membrane (OR 3.46, 1.04–6.45), maternal medical disorders (OR 3.13, 1.56–5.16), body mass index at delivery of less than 23 (OR 3.01, 1.56–5.43), antepartum haemorrhage (OR 2.73, 1.18–6.34), maternal febrile illness (OR 2.84, 1.32–4.52), intrauterine growth retardation (OR 2.14, 0.98–2.34) and multiple pregnancy (OR 1.98, 1.02–2.68) remained as significant factors.
Serum 25‐hydroxyvitamin D and insulin resistance in people at high risk of cardiovascular disease: a euglycaemic hyperinsulinaemic clamp study

In observational studies, low serum 25‐hydroxyvitamin D (25‐OHD) concentration is associated with an increased risk of type 2 diabetes mellitus (DM). Increasing serum 25‐OHD may have beneficial effects on insulin resistance or beta‐cell function. Cross‐sectional studies utilizing suboptimal methods for assessment of insulin sensitivity and serum 25‐OHD concentration provide conflicting results.
Utilization of Acetate by Beggiatoa

Burton, Sheril D. (Institute of Marine Science, University of Alaska, College), Richard Y. Morita, and Wayne Miller. Utilization of acetate by Beggiatoa. J. Bacteriol. 91:1192–1200. 1966. —A proposed system which would permit acetate incorporation into four-carbon compounds without the presence of key enzymes of the citric acid cycle or glyoxylate cycle is described. In this system, acetyl-coenzyme A (CoA) is condensed with glyoxylate to form malate, which, in turn, is converted to oxaloacetate. Oxaloacetate then reacts with glutamate to produce α-ketoglutarate, which is subsequently converted to isocitrate. Cleavage of isocitrate produces glyoxylate and succinate. Thus, the proposed system is similar to the glyoxylate bypass in that malate is produced from glyoxylate and acetyl-CoA, but differs from both the citric acid cycle and the glyoxylate bypass, since citrate and fumarate are not involved. Fumarase, aconitase, catalase, citritase, pyruvate kinase, enolase, phosphoenolpyruvate carboxylase, lactic dehydrogenase, α-ketoglutarate dehydrogenase, and condensing enzyme were not detectable in crude extracts of Beggiatoa. Succinate was oxidized by a soluble enzyme not associated with an electron-transport particle. Isocitrate was identified as the sole compound labeled when C14O2 was added to a reduced nicotinamide adenine dinucleotide, CO2 generating system (crystalline glucose-6-phosphate dehydrogenase and glucose-6-phosphate) in the presence of α-ketoglutarate.
Assessment of the protective effect of pneumococcal vaccination in preventing meningitis after cochlear implantation.

OBJECTIVES To examine if a 23-valent pneumococcal capsular polysaccharide vaccine (PPV23) reduces the risk of meningitis in healthy rats after cochlear implantation. DESIGN Interventional animal study. INTERVENTIONS Thirty-six rats (18 immunized and 18 unimmunized) received cochlear implantations and were then infected with Streptococcus pneumoniae via 3 different routes (hematogenous, middle ear, and inner ear) in numbers sufficient to induce meningitis. RESULTS The rats with implants that received PPV23 were protected from meningitis when the bacteria were delivered via the hematogenous and middle-ear routes (Fisher exact test P<.05). However, the protective effect of the vaccine in the rats with implants was only moderate when the bacteria were inoculated directly into the inner ear. CONCLUSIONS Our animal model clearly demonstrates that immunization can protect healthy rats with a cochlear implant from meningitis caused by a vaccine-covered serotype. This finding supports the notion that all current and future implant recipients should be vaccinated against S pneumoniae.
Evaluation of the survival prediction index as a model of risk stratification for clinical research in dogs admitted to intensive care units at four locations.

OBJECTIVE To prospectively evaluate a survival prediction index (SPI) in dogs admitted to intensive care units (ICU) and to generate and test an improved SPI (ie, SPI2). SAMPLE POPULATION Medical records of 624 critically ill dogs admitted to an ICU. PROCEDURE Data were collected from dogs within 24 hours after admission to an ICU. Variables recorded reflected function of vital organ systems, severity of underlying physiologic derangement, and extent of physiologic reserve; outcome was defined as dogs that survived or did not survive until 30 days after admission to the ICU. Probabilities of survival were calculated, using an established model (SPI). We then performed another logistic regression analysis, thereby reestimating the variables to create the new SPI2. Cross-validation of the models obtained was performed by randomly assigning the total sample of 624 dogs into an estimation group of 499 dogs and validation group of 125 dogs. RESULTS Testing of SPI resulted in an area under the curve (AUC) of 0.723. Testing of SPI2 revealed an AUC of 0.773. A backwards-elimination procedure was used to create a model containing fewer variables, and variables were sequentially eliminated. The AUC for the reduced model of SPI2 was 0.76, indicating little loss in predictive accuracy. CONCLUSIONS AND CLINICAL RELEVANCE The new SPI2 objectively stratified clinical patients into groups according to severity of disease. This index could provide an important tool for clinical research.
Gender Differences in Mortality After Hip Fracture: The Role of Infection

Possible explanations for the observed gender difference in mortality after hip fracture were examined in a cohort of 804 men and women. Mortality during 2 years after fracture was identified from death certificates. Men were twice as likely as women to die, and deaths caused by pneumonia/influenza and septicemia showed the greatest increase.
Mean-field study of the Bose-Hubbard model in the Penrose lattice

We examine the Bose-Hubbard model in the Penrose lattice based on inhomogeneous mean-field theory. Since averaged coordination number in the Penrose lattice is four, mean-field phase diagram consisting of the Mott insulator (MI) and superfluid (SF) phase is similar to that of the square lattice. However, the spatial distribution of Bose condensate in the SF phase is significantly different from uniform distribution in the square lattice. We find a fractal structure in its distribution near the MI-SF phase boundary. The emergence of the fractal structure is a consequence of cooperative effect between quasiperiodicity in the Penrose lattice and criticality at the phase transition.
Hysteresis of the PTH‐calcium curve during hypocalcemia in the dog: Effect of the rate and linearity of calcium decrease and sequential episodes of hypocalcemia

Several studies have shown the presence of hysteresis of the parathyroid hormone (PTH)‐calcium relationship in both normal humans and hemodialysis patients; for hypocalcemia, hysteresis is defined as a lower PTH level for the same serum calcium during the recovery from than the induction of hypocalcemia. However, some have questioned whether hysteresis is only a function of the rate and/or direction of change in calcium, and others have proposed that hysteresis is due to depletion of PTH stores. To address these issues, two groups of dogs were studied. To induce hypocalcemia, sodium EDTA (50 mg/kg) was infused either over 60 (termed slow) or 30 (termed fast) minutes; immediately after the cessation of the ethylenediamine tetracetate (EDTA) infusion, calcium chloride (0.75 mEq/kg) was infused over 60 or 30 minutes, respectively, to correct the hypocalcemia. The EDTA infusion produced a linear decrease in serum calcium by progressively increasing the infusion rate at regular intervals. A second cycle of hypocalcemia and recovery using the same protocol was started immediately after the completion of the first cycle. To determine whether a nonlinear decrease in the serum calcium affected the PTH response to hypocalcemia, a third group of dogs, termed superfast, was studied; in this group, EDTA was infused for 30 minutes at a constant rate of 50 mg/kg. The hysteretic loops of PTH produced by the two sequential slow and fast cycles and the superfast cycle during the induction of and recovery from hypocalcemia were similar. Moreover, the maximal PTH level for the two sequential slow and fast cycles and the superfast cycle was not different even though the rates of calcium decrease varied and the calcium decrease was nonlinear in the superfast cycle. In conclusion, (1) since hysteresis was reproducible and the maximal PTH was not different during two sequential cycles of hypocalcemia, hysteresis is not due to PTH depletion; (2) the PTH‐calcium curve is not affected by the rate at which hypocalcemia is induced: and (3) the maximal PTH level is not influenced by either the rate or linearity of the reduction in serum calcium.
Economic Impact of a Drug Information Service

OBJECTIVE: A cost-avoidance model was developed to determine potential cost savings or “avoidance” that results from a drug information service (DIS) responding to drug information requests. DESIGN: Patient-specific questions received by the DIS were reviewed and evaluated. A panel determined whether a drug misadventure event may have occurred if the DIS had not been consulted. Potential outcomes from drug information requests were classified using a decision-tree model. A severity rating was then attached to each applicable request to predict potential cost savings of the DIS. RESULTS: Seventy-seven of the 570 drug information responses received in the six-week study period had assessable potential cost savings to the institution. During the study interval, potential cost savings were estimated to be $195 000. Projected to one year, potential cost savings reached $1.7 million. Of the savings noted, most were attributable to prevention of increased monitoring or additional treatment. Using a sensitivity analysis, annual potential cost savings ranged from $417 792 to $2 052 740 per year. Based on the estimated annual costs related to maintaining a DIS of $145 950, the resultant range of benefit/cost ratio is 2.9:1 to 13.2:1. CONCLUSIONS: This model demonstrates that the DIS at our institution provides potential cost savings. This model may be modified to evaluate potential cost savings in other areas of pharmacy practice.
AutoCLINT: The Winning Method in AutoCV Challenge 2019

NeurIPS 2019 AutoDL challenge is a series of six automated machine learning competitions. Particularly, AutoCV challenges mainly focused on classification tasks on visual domain. In this paper, we introduce the winning method in the competition, AutoCLINT. The proposed method implements an autonomous training strategy, including efficient code optimization, and applies an automated data augmentation to achieve the fast adaptation of pretrained networks. We implement a light version of Fast AutoAugment to search for data augmentation policies efficiently for the arbitrarily given image domains. We also empirically analyze the components of the proposed method and provide ablation studies focusing on AutoCV datasets.
Multiary α-Resolution Principle for a Lattice-Valued Logic

This paper focuses on resolution-based automated reasoning theory in a lattice-valued logic system with truth values that are defined in a lattice-valued logical algebraic structure-lattice implication algebras (LIAs) - which essentially aims to extend the classical logic to handle automated deduction under an uncertain environment. Concretely, we investigate a generalization of the known conjunctive normal form (CNF) in the classical logic representation that we call the generalized conjunctive normal form (GCNF), which aims to characterize the constants and implication connectives that are essentially different from the ones in classical logic. We then extend the established resolution principle at a certain truth-value level α (called α-resolution) in this lattice-valued logic to a more general form, i.e., from binary α -resolution to multiary α-resolution. The extension to multiary α-resolution starts from lattice-valued propositional logic LP(X), while its theorems of both soundness and completeness are proved. Multiary α-resolution principle is then further established in the corresponding lattice-valued first-order logic LF(X), along with its soundness theorem, lifting lemma, and completeness theorem. Meanwhile, an important result that multiary α-resolution principle in LF(X) can be equivalently transformed into that in LP(X) to some extent is obtained. All these works will theoretically support the establishment of an automated reasoning algorithm and its implementation with further applications into automated deduction and decision-making problems under uncertainty.
Clinical Impact and Course of Anticoagulant-Related Major Bleeding in Cancer Patients

Abstract Cancer patients with venous thromboembolism (VTE) have a two- to six-fold increased risk of anticoagulant-related major bleeding events compared with VTE patients without cancer. It is unknown whether major bleeding events are more severe in cancer patients than in those without cancer. Individual patient data from four randomized phase III trials that compared factor Xa inhibitors and vitamin K antagonists for the treatment of VTE were used to compare the severity of major bleeding events in patients with and without cancer. Using predefined criteria, the severity of the clinical presentation and course of major bleeding events were classified into four categories of increasing severity. A one-stage meta-analysis was used to evaluate the effect of cancer on the severity of the clinical presentation and course by estimating crude odds ratios (ORs) and ORs adjusted for age, sex and anticoagulant type with 95% confidence intervals (CIs). The study group comprised 290 patients with major bleeding, of whom 50 (17%) had cancer. The clinical presentation was judged to be severe (category 3 or 4) in 38% of patients with cancer and 44% of patients without cancer (adjusted OR, 0.90; 95% CI, 0.47–1.72). The clinical course was found to be severe in 20 and 25% of patients with and without cancer, respectively (adjusted OR, 0.75; 95% CI, 0.35–1.61). The present study suggests that the clinical presentation and course of anticoagulant-related major bleeding events are not more severe in cancer patients than in patients without cancer. This may be reassuring for physicians who treat cancer patients with anticoagulant-related bleeding.
Cross-Sectional Association between Polyfluoroalkyl Chemicals and Cognitive Limitation in the National Health and Nutrition Examination Survey

Background/Aims: Our limited understanding of how polyfluoroalkyl chemicals (PFCs) may impact on human health suggests the potential for a protective impact on brain health. This study was designed to explore the association between PFCs and cognitive ability in older adults. Methods: We assessed the association between four PFCs, perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorononanoic acid (PFNA) and perfluorohexane sulfonic acid (PFHxS), and self-reported limitation due to difficulty remembering or periods of confusion using data from participants aged 60–85 years from the 1999–2000 and 2003–2008 National Health and Nutrition Examination Surveys. We also considered whether diabetic status or diabetic medication use modifies this association in light of in vitro evidence that PFCs may act on the same receptors as some diabetic medications. Results: In multivariable adjusted models, point estimates suggest a protective association between PFCs and self-reported cognitive limitation (odds ratio, OR; 95% confidence interval, CI) for a doubling in PFC concentration: PFOS (OR, 0.90; 95% CI, 0.78, 1.03), PFOA (OR, 0.92; 95% CI, 0.78, 1.09), PFNA (OR, 0.91; 95% CI, 0.79, 1.04) and PFHxS (OR, 0.93; 95% CI, 0.82, 1.06). The protective association was concentrated in diabetics, with strong, significant protective associations in nonmedicated diabetics. Conclusions: This cross-sectional study suggests that there may be a protective association between exposure to PFCs and cognition in older adults, particularly diabetics.
Glucagon-mediated impairments in hepatic and peripheral tissue nutrient disposal are not aggravated by increased lipid availability.

Glucose, fat, and glucagon availability are increased in diabetes. The normal response of the liver to chronic increases in glucose availability is to adapt to become a marked consumer of glucose. Yet this fails to occur in diabetes. The aim was to determine whether increased glucagon and lipid interact to impair the adaptation to increased glucose availability. Chronically catheterized well controlled depancreatized conscious dogs (n = 21) received 3 days of continuous parenteral nutrition (TPN) that was either high in glucose [C; 75% nonprotein calories (NPC)] or in lipid (HL; 75% NPC) in the presence or absence of a low dose (one-third basal) chronic intraportal infusion of glucagon (GN; 0.25 ng.kg(-1). min(-1)). During the 3 days of TPN, all groups received the same insulin algorithm; the total amount of glucose infused (GIR) was varied to maintain isoglycemia ( approximately 120 mg/dl). On day 3 of TPN, hepatic metabolism was assessed. Glucose and insulin levels were similar in all groups. GIR was decreased in HL and C + GN ( approximately 30%) and was further decreased in HL + GN (55%). Net hepatic glucose uptake was decreased approximately 15% in C + GN, and HL and was decreased approximately 50% in HL + GN. Lipid alone or combined with glucagon decreased glucose uptake by peripheral tissues. Despite impairing whole body glucose utilization, HL did not limit whole body energy disposal. In contrast, glucagon suppressed whole body energy disposal irrespective of the diet composition. In summary, failure to appropriately suppress glucagon secretion adds to the dietary fat-induced impairment in both hepatic and peripheral glucose disposal. In addition, unlike increasing the percentage of calories as fat, inappropriate glucagon secretion in the absence of compensatory hyperinsulinemia limits whole body nutrient disposition.
The Role of LIP5 and CHMP5 in Multivesicular Body Formation and HIV-1 Budding in Mammalian Cells*

We examined the function of LIP5 in mammalian cells, because the yeast homologue Vta1p was recently identified as a protein required for multivesicular body (MVB) formation. LIP5 is predominantly a cytosolic protein. Depletion of LIP5 by small inhibitory RNA (siRNA) does not affect the distribution or morphology of early endosomes, lysosomes, or Golgi but does reduce the degradation of internalized epidermal growth factor receptor (EGFR), with EGFR accumulating in intracellular vesicles. Depletion of LIP5 by siRNA also decreases human immunodeficiency virus type 1 (HIV-1) budding by 70%. We identify CHMP5 as a LIP5-binding protein and show that CHMP5 is primarily cytosolic. Depletion of CHMP5 by siRNA does not affect the distribution or morphology of early endosomes, lysosomes, or Golgi but does result in reduced degradation of the EGFR similar to silencing of LIP5. Surprisingly, CHMP5 depletion results in an increase in the release of infectious HIV-1 particles. Overexpression of CHMP5 with a large carboxyl-terminal epitope affects the distribution of both early and late endocytic compartments, whereas overexpression of LIP5 does not alter the endocytic pathway. Comparison of overexpression and siRNA phenotypes suggests that the roles of these proteins in MVB formation may be more specifically addressed using RNA interference and that both LIP5 and CHMP5 function in MVB sorting, whereas only LIP5 is required for HIV release.