Miracle-dz/UniFAR-FTUs huggingface dataset:
Metallothionein plays less of a protective role in cadmium-metallothionein-induced nephrotoxicity than in cadmium chloride-induced hepatotoxicity.

Metallothioneins (MTs) are low-molecular weight, cysteine-rich, metal-binding proteins. Pretreatment of animals with Zn increases tissue MT concentrations, and protects against Cd-induced toxicity. However, Zn treatment produces many effects in addition to increasing MT. Therefore, MT-I and -II knock-out (MT-null) mice were used to determine the roles of MT in Cd-induced hepatotoxicity and nephrotoxicity, as well as in Zn-induced protection. MT-null mice were more sensitive to CdCl2 (25 mumol/kg i.p.) hepatotoxicity, as evidenced by 25-fold increases in serum alanine aminotransferase activity, compared to 12-fold increases in control mice. Zn pretreatment (200 mumol/kg s.c. x 2 days) increased hepatic MT 80 fold in control mice but not in MT-null mice, and prevented CdCl2 hepatotoxicity in control mice only. It is concluded that MT plays a critical role in Cd-induced hepatotoxicity. In contrast to CdCl2-induced hepatotoxicity, MT-null mice were equally susceptible as controls to the Cd-MT (CdMT) (0.1-0.4 mg Cd/kg i.v.) nephrotoxicity, as evidenced by similar increases in urinary protein (up to 30-fold) and glucose excretion (up to 60-fold), as well as similar extent of proximal tubular necrosis. Zn increased renal MT (28-fold) in control mice only; however, it protected against CdMT-induced renal injury in both control and MT-null mice. These findings suggest that MT plays less of a protective role in protecting against CdMT-induced nephrotoxicity than CdCl2-induced hepatotoxicity, and that Zn-induced protection against CdMT-induced nephrotoxicity does not appear to be mediated through MT.
Analysis of the Permeability Characteristics of Cat Intestinal Capillaries

The permeability characteristics of cat small intestine capillaries were studied using both osmotic transient and lymph-to-plasma protein concentration ratio (L/P) techniques, A vascularly perfused segment of ileum in which superior mesenteric arterial pressure, blood flow, superior mesenteric venous pressure, and lymph flow were monitored was used for both determinations. Intestinal volume was continuously monitored during the osmotic transient experiments. Hyperosmotic solutions of various test solutes were infused at a constant rate directly into the superior mesenteric artery after the establishment of an isovolumetric state. Osmotic conductances were calculated from the initial rate of volume loss and the calculated plasma osmotic pressure change. Reflection coefficients for the various solutes were determined from the osmotic conductance and filtration coefficients within the same preparation. The predicted equivalent pore radius for intestinal capillaries using this approach is 200-350 A. In another group of cats, the L/P ratio for total plasma proteins was determined prior to and following graded increases in intestinal venous outflow pressure (10-30 mm Hg). At the greatest dilution of lymph proteins, the minimum osmotic reflection coefficient for total plasma proteins (ap) was estimated assuming ap = 1 - (Ci/Cp), and values of op between 0.87 and 0.92 were acquired. Minimum osmotic reflection coefficients for total plasma proteins were then determined during osmotic transients induced by hypertonic glucose (20-70 MM). Values of op between 0.56 and 0.74 were acquired during the osmotic transients. The results of these studies suggest that intestinal capillaries are relatively impermeable to endogenous plasma proteins. The discrepancy between the L/P ratio and osmotic transient techniques results, at least in part, from an increased capillary permeability during the osmotic transient. Circ Res 44: 335-344, 1979
Methodological Choices in Muscle Synergy Analysis Impact Differentiation of Physiological Characteristics Following Stroke

Muscle synergy analysis (MSA) is a mathematical technique that reduces the dimensionality of electromyographic (EMG) data. Used increasingly in biomechanics research, MSA requires methodological choices at each stage of the analysis. Differences in methodological steps affect the overall outcome, making it difficult to compare results across studies. We applied MSA to EMG data collected from individuals post-stroke identified as either responders (RES) or non-responders (nRES) on the basis of a critical post-treatment increase in walking speed. Importantly, no clinical or functional indicators identified differences between the cohort of RES and nRES at baseline. For this exploratory study, we selected the five highest RES and five lowest nRES available from a larger sample. Our goal was to assess how the methodological choices made before, during, and after MSA affect the ability to differentiate two groups with intrinsic physiologic differences based on MSA results. We investigated 30 variations in MSA methodology to determine which choices allowed differentiation of RES from nRES at baseline. Trial-to-trial variability in time-independent synergy vectors (SVs) and time-varying neural commands (NCs) were measured as a function of: (1) number of synergies computed; (2) EMG normalization method before MSA; (3) whether SVs were held constant across trials or allowed to vary during MSA; and (4) synergy analysis output normalization method after MSA. MSA methodology had a strong effect on our ability to differentiate RES from nRES at baseline. Across all 10 individuals and MSA variations, two synergies were needed to reach an average of 90% variance accounted for (VAF). Based on effect sizes, differences in SV and NC variability between groups were greatest using two synergies with SVs that varied from trial-to-trial. Differences in SV variability were clearest using unit magnitude per trial EMG normalization, while NC variability was less sensitive to EMG normalization method. No outcomes were greatly impacted by output normalization method. MSA variability for some, but not all, methods successfully differentiated intrinsic physiological differences inaccessible to traditional clinical or biomechanical assessments. Our results were sensitive to methodological choices, highlighting the need for disclosure of all aspects of MSA methodology in future studies.
When looks can kill: the evolution of sexually dimorphic floral display and the extinction of dioecious plants

Dioecious plants (with separate male and female individuals) more often have drab, inconspicuous flowers than related bisexual plants. Models indicate, however, that similar conditions favour the evolution of showy floral displays in dioecious and bisexual plants. One difference, however, is that dioecious plants may evolve floral displays that are sexually dimorphic. We show that males are more likely to evolve showy flowers than females in animal–pollinated plants, especially when pollinators are abundant. We demonstrate that this dimorphism places showy dioecious plants at a much higher risk of extinction during years of low pollinator abundance because pollinators may fail to visit female flowers. The higher extinction risk of showy dioecious plants provides an explanation for the fact that dioecious plants that do persist tend to have inconspicuous flowers and are more often wind pollinated. It may also help explain why dioecious plants are less species-rich than related bisexual plants.
Shortened questionnaires to assess anxiety and depression during in-hospital rehabilitation: clinical validation and cutoff scores

Background A postacute phase needs reliable routine screening instruments in order to identify the patients to be referred for a clinical interview with a psychologist. The aim of this study was to estimate the clinical cutoff scores of the anxiety and depression questionnaires and their clinical validity using a gold standard. Methods The study involved 177 patients with pulmonary, cardiac, or neurological disease undergoing in-hospital rehabilitation. Receiver operating characteristic curves were used to determine the best concordance between questionnaire’s scores and the gold standards. Results There was a significant difference (P<0.001) between clinically anxious and depressed patients and nonclinical subjects. The receiver operating characteristic curve for anxiety indicated that the best area under the curve for State Anxiety Inventory is obtained with a cutoff point of 21 for males and 25 for females; for depression scores, the highest area under the curve for Depression Questionnaire-Reduced Form is obtained with a cutoff point of six for males and eight for females. Conclusion Using appropriate cutoff values, the State Anxiety Inventory and Depression Questionnaire-Reduced Form allow psychologists to optimize early clinical intervention strategies selecting patients with significant needs.
Stable Complexes Involving Acetylcholinesterase and Amyloid-β Peptide Change the Biochemical Properties of the Enzyme and Increase the Neurotoxicity of Alzheimer’s Fibrils

Brain acetylcholinesterase (AChE) forms stable complexes with amyloid-β peptide (Aβ) during its assembly into filaments, in agreement with its colocalization with the Aβ deposits of Alzheimer’s brain. The association of the enzyme with nascent Aβ aggregates occurs as early as after 30 min of incubation. Analysis of the catalytic activity of the AChE incorporated into these complexes shows an anomalous behavior reminiscent of the AChE associated with senile plaques, which includes a resistance to low pH, high substrate concentrations, and lower sensitivity to AChE inhibitors. Furthermore, the toxicity of the AChE–amyloid complexes is higher than that of the Aβ aggregates alone. Thus, in addition to its possible role as a heterogeneous nucleator during amyloid formation, AChE, by forming such stable complexes, may increase the neurotoxicity of Aβ fibrils and thus may determine the selective neuronal loss observed in Alzheimer’s brain.
Thalidomide regulation of NF-κB proteins limits Tregs activity in chronic lymphocytic leukemia.

BACKGROUND Thalidomide may represent a novel therapeutic strategy in the treatment of chronic lymphocytic leukemia (CLL). Since the activation of nuclear factor kappa B (NF-κB) causes not only malignant transformation and tumor progression, but also allows tumor cells to evade immune surveillance, NF-κB signaling components might constitute a potential target for future therapy in CLL. OBJECTIVES The current study is an attempt to characterize proteins regulated by thalidomide. Thalidomide's influence on NF-κB proteins and on regulatory T cells (Treg) in CLL was investigated. MATERIAL AND METHODS A total of 15 patients with CLL were treated with a combined thalidomide/fludarabine regimen. Peripheral blood mononuclear cells were separated by Ficoll density gradient centrifugation. To evaluate glucocorticoid induced tumour-necrosis-factor-receptor-related protein (GITR) expression in regulatory T cells, cells incubated with anti-CD3, ani-CD4 and anti-CD25 were permeabilized and then stained with anti-FOXP3 and analyzed using flow cytometry. Human TNF enzyme-linked immunosorbent assay (ELISA) was used to determine the tumor necrosis factor (TNF) levels in the serum. To evaluate NF-κB activity, chemiluminescent oligonucleotide-based ELISA was performed. RESULTS It was found that thalidomide regulates NF-κB activity differentially, and the activity of certain NF-κB components correlated with TNF levels and T regulatory cell (CD4 + CD25 high GITR + ). CONCLUSIONS These results might indicate that thalidomide not only regulates TNF but also directly interferes with NF-κB components.
Written production in a case of locked-in syndrome with bilateral corticopontic degeneration

Patients in locked-in syndrome show normal or near normal mental abilities that contrast with the limited motor capacity that hinders voluntary communication. However, eye movements and blinking are usually preserved and can be used to establish a communication system. We report an exceptional case of locked-in syndrome. The aetiology was basilar thrombosis consecutive to a cervical manipulation. In addition, brain MRI performed 23 years later showed a ventral pontine stroke with bilateral corticopontic degeneration. In this study the patient was able to produce written output using a chin-controlled Morse system decoded by a computer. A detailed linguistic analysis of text written over 20 years by the patient was carried out. The data demonstrate that improvements in language performance can be observed even in patients with brain lesions in areas associated with high-level cognitive processes. The data show a decrease of typing, grammatical and lexical errors over time, use of less frequent words, and an increase of more complex linguistic structures. This paper adds to previous findings confirming the value of daily practice and rehabilitation to enhance quality of life in this group of patients.
Biodistribution of Radiolabeled, Formulated Gadopentetate, Gadoteridol, Gadoterate, and Gadodiamide in Mice and Rats

RATIONALE AND OBJECTIVES. The authors studied the long-term distribution of gadolinium (Gd) in mice and rats after the administration of four commercially available magnetic resonance imaging contrast media. The goals were to determine any possible product dissociation in vivo and to evaluate the effects that product excipients had on the tissue distributions. METHODS. Gadolinium-153 (153Gd)-labeled gadopentetate (Magnevist), gadoteridol (ProHance), gadoterate (Dotarem), and gadodiamide (Omniscan) were administered intravenously to mice (0.48 mmol/kg) and rats (0.1 mmol/kg). At various times up to 14 days posttreatment, the residual 153Gd was measured in selected tissues. The tissue distributions obtained were used to make intra- and interchelate distribution evaluations and comparisons regarding tissue clearance and any possible in vivo dissociation of the Gd chelates. RESULTS.Differences were found among the chelates studied relative to the amounts of residual 153Gd present in tissues known to sequester free Gd, particularly in liver and femur at 7 and 14 days after administration, in both mice and rats. The pattern of the 153Gd distribution suggested that the linear chelates, gadopentetate and gadodiamide, dissociated in vivo resulting in more 153Gd present in bone and liver at the longer residence times than in the subjects injected with the macrocyclic chelates, gadoteridol and gadoterate. The only excipient found to affect the distribution profile was calcium(DTPA-BMA); this excipient in formulated gadodiamide decreased the amounts of residual Gd measured in whole body, bone, and liver in mice compared with levels obtained when gadodiamide was injected alone. CONCLUSIONS.The molecular feature found to be most important in differentiating the four chelates evaluated is the presence or absence of a macrocyclic structure. The Gd chelates containing this structure, gadoteridol and gadoterate, have the lowest residual Gd at long residence times in both mice and rats. The order of residual whole body Gd at 14 days (lowest to highest) was: gadoteridol ~ gadoterate ≤ gadopentetategadodiamide. The only excipient that affected the biodistribution was found in the gadodiamide formulation where the addition of 5% calcium (DTPA-BMA) reduced residual Gd to just less than 10 times greater than that found for the macrocyclic chelates with the lowest residual Gd, gadoteridol and gadoterate.
Video Acceleration Magnification

The ability to amplify or reduce subtle image changes over time is useful in contexts such as video editing, medical video analysis, product quality control and sports. In these contexts there is often large motion present which severely distorts current video amplification methods that magnify change linearly. In this work we propose a method to cope with large motions while still magnifying small changes. We make the following two observations: i) large motions are linear on the temporal scale of the small changes, ii) small changes deviate from this linearity. We ignore linear motion and propose to magnify acceleration. Our method is pure Eulerian and does not require any optical flow, temporal alignment or region annotations. We link temporal second-order derivative filtering to spatial acceleration magnification. We apply our method to moving objects where we show motion magnification and color magnification. We provide quantitative as well as qualitative evidence for our method while comparing to the state-of-the-art.
Missense mutations in the insulin promoter factor-1 gene predispose to type 2 diabetes

The transcription factor insulin promoter factor-1 (IPF-1) plays a central role in both the development of the pancreas and the regulation of insulin gene expression in the mature pancreatic β cell. A dominant-negative frameshift mutation in the IPF-l gene was identified in a single family and shown to cause pancreatic agenesis when homozygous and maturity-onset diabetes of the young (MODY) when heterozygous. We studied the role of IPF-1 in Caucasian diabetic and nondiabetic subjects from the United Kingdom. Three novel IPF-1 missense mutations (C18R, D76N, and R197H) were identified in patients with type 2 diabetes. Functional analyses of these mutations demonstrated decreased binding activity to the human insulin gene promoter and reduced activation of the insulin gene in response to hyperglycemia in the human β-cell line Nes2y. These mutations are present in 1% of the population and predisposed the subject to type 2 diabetes with a relative risk of 3.0. They were not highly penetrant MODY mutations, as there were nondiabetic mutation carriers 25‐53 years of age. We conclude that mutations in the IPF-1 gene may predispose to type 2 diabetes and are a rare cause of MODY and pancreatic agenesis, with the phenotype depending upon the severity of the mutation. J. Clin. Invest. 104:R33-R39 (1999).
Characteristics of vacuum breakdown field and comparison of field enhancement factor β in CuCr electrodes with slit configuration

A contact electrode of vacuum interrupter (VI) has slit parts on the electrode surface to control the vacuum arc during the current interruption. The edge configuration of the slit is important for the withstand performance of high voltage application for VI. We investigated the effect of the curvature radius of slit's configuration on the field enhancement factor β and the characteristics of vacuum breakdown for the slit electrodes made of CuCr alloy simplified simulating the AMF-electrode. As the results, the round chamfered configuration at the edge of slit increases the breakdown field, because of the reduction of pre-breakdown current flowing, that is, small field emission current. This is due to be small β-value by rounding chamfering of the edge at the slit. The BD field of the slit electrode can be improved by rounding the edge of the end of the slit more than 1 mm curvature radius, and the curvature of 0.5 mm radius for R0.5 slit electrode had almost little effect on improving the BD field owing to manufacturing inadequate curvature at the edge of slit.
[Comparison of nalbuphine and pentazocine in the treatment of postoperative pain by self-administration].

The side-effects of two opioid agonist-antagonists, nalbuphine and pentazocine, were assessed when used for patient-controlled postoperative analgesia. Forty ASA I or II patients scheduled for upper abdominal surgery were randomly allocated to two equal groups. The anaesthetic technique was the same for all the patients: premedication with atropine and diazepam, induction with thiopentone and suxamethonium and maintenance with fentanyl, pancuronium, nitrous oxide and halothane. Patient-controlled computer assisted analgesia (On-Demand Analgesia Computer) was started in the recovery room at least 2 h after the last administration of fentanyl. The parameters used were: a routine hourly dose (the half of that received during the previous hour), with on demand delivery of nalbuphine (15 micrograms.kg-1) or pentazocine (45 micrograms.kg-1) aliquots respectively, with a refractory period between two demands of 4 min and a total hourly maximum dose of 16 mg and 48 mg respectively. The following parameters were measured before the start of self-administration, and every hour afterwards for 24 h: systolic (Pasys) and diastolic blood pressures, heart rate, pressure-rate product (PRP), respiratory rate, end-tidal CO2 and pain (by way of a three point scale). Analgesia was assessed on a four-point scale every 6 h. The total doses of nalbuphine and pentazocine administered were 94 +/- 43 mg and 251 +/- 150 mg respectively. The only parameters significantly different between the two groups were Pasys and PRP, being higher in the pentazocine group. There were no significant differences in the side-effects (drowsiness, nausea, vomiting, headache, amnesia, logorrhoea and urine retention). All patients in both groups were satisfied with this technique. (ABSTRACT TRUNCATED AT 250 WORDS)
The role of centralized reading of endoscopy in a randomized controlled trial of mesalamine for ulcerative colitis.

BACKGROUND & AIMS Interobserver differences in endoscopic assessments contribute to variations in rates of response to placebo in ulcerative colitis (UC) trials. We investigated whether centralized review of images could reduce these variations. METHODS We performed a 10-week, randomized, double-blind, placebo-controlled study of 281 patients with mildly to moderately active UC, defined by an Ulcerative Colitis Disease Activity Index (UCDAI) sigmoidoscopy score ≥2, that evaluated the efficacy of delayed-release mesalamine (Asacol 800-mg tablet) 4.8 g/day. Endoscopic images were reviewed by a single expert central reader. The primary outcome was clinical remission (UCDAI, stool frequency and bleeding scores of 0, and no fecal urgency) at week 6. RESULTS The primary outcome was achieved by 30.0% of patients treated with mesalamine and 20.6% of those given placebo, a difference of 9.4% (95% confidence interval [CI], -0.7% to 19.4%; P = .069). Significant differences in results from secondary analyses indicated the efficacy of mesalamine. Thirty-one percent of participants, all of whom had a UCDAI sigmoidoscopy score ≥2 as read by the site investigator, were considered ineligible by the central reader. After exclusion of these patients, the remission rates were 29.0% and 13.8% in the mesalamine and placebo groups, respectively (difference of 15%; 95% CI, 3.5%-26.0%; P = .011). CONCLUSIONS Although mesalamine 4.8 g/day was not statistically different from placebo for induction of remission in patients with mildly to moderately active UC, based on an intent-to-treat analysis, the totality of the data supports a benefit of treatment. Central review of endoscopic images is critical to the conduct of induction studies in UC; ClinicalTrials.gov Number, NCT01059344.
A sufficient condition for the boundedness of operator-weighted martingale transforms and Hilbert transform

Let W be an operator weight taking values almost everywhere in the bounded positive invertible linear operators on a separable Hilbert space H. We show that if W and its inverse W −1 both satisfy a matrix reverse Holder property introduced by Christ and Goldberg, then the weighted Hilbert transform H : L 2(R,H) ! L 2(R,H) and also all weighted dyadic martingale transforms T� : L 2(R,H) ! L 2(R,H) are bounded. We also show that this condition is not necessary for the boundedness of the weighted Hilbert transform.
Chemotherapy of a malignant, metastasizing giant‐cell tumor of bone. Report of an unusual case and the response to combination chemotherapy

A 13‐year‐old girl was treated surgically for a giant‐cell tumor of bone originating in the talus and for a recurrence in the distal tibia. She later developed liver and lung metastases and was treated for two years, five months with a combination of vincristine, doxorubicin, cyclophosphamide and actinomycin‐D, and thereafter with high‐dose methotrexate/vincristine with citrovorum factor rescue. A good response was obtained and the patient is without evidence of disease 12 months after a salvage thoracotomy for residual disease in the left lung. Aspects of this singular case are discussed.