Miracle-dz/UniFAR-FTUs huggingface dataset:
Combination Therapy with Thalidomide, Incadronate, and Dexamethasone for Relapsed or Refractory Multiple Myeloma

The feasibility and efficacy of a combination of thalidomide, incadronate, and dexamethasone (TID) were studied in 12 patients with relapsed or refractory multiple myeloma. The protocol, consisting of 300 mg/day of thalidomide administered orally, intravenous incadronate (10 mg/day) administered weekly, and 12 mg/day dexamethasone for 4 days, was repeated every 3 weeks. Evaluations of efficacy and toxicity were carried out every 3 weeks and were continued for 3 cycles. Three patients were excluded during the study because of apnea, severe somnolence, and pancytopenia. Of 9 evaluated patients, the partial responses achieved in 3 patients and the minor responses achieved in 4 patients corresponded to a response rate of 78% according to the criteria of the European Group for Blood and Marrow Transplantation. In addition, painful osteolytic symptoms improved rapidly after 1 cycle of TID therapy in the 10 patients evaluated. These data suggest that TID is a feasible and promising therapeutic approach for refractory and relapsed multiple myeloma.
The interface between phonetic and lexical abilities in early Cantonese language development

Data from the Cantonese Communicative Development Inventory (CCDI) is used to review the phonological preferences of younger (16–22 months) and older (23–30 month) groups of children in the lexical items they are reported to be able to say. Analogous results to those found for English emerge from the Cantonese data: the younger group display selectivity in the initial consonants of words they say, and their preferences accord with developmental tendencies in Cantonese phonology. From children whose scores fell below the tenth percentile of the CCDI, a subset were followed up 1 year later and their linguistic progress evaluated. Only a proportion of these children were below still below the tenth percentile for vocabulary at follow‐up. Their lexical immaturities were accompanied by limited phonetic abilities. The implications of the findings are discussed.
Learning-facilitated long-term depression and long-term potentiation at mossy fiber—CA3 synapses requires activation of β-adrenergic receptors

Learning-facilitated plasticity refers to hippocampal synaptic plasticity that is facilitated by novel spatial learning events. Both long-term potentiation (LTP) and long-term depression (LTD) are facilitated by novel hippocampus-dependent learning. This has important ramifications for our understanding of how the hippocampus encodes memory. One structure that is rarely studied in vivo, but is believed to be crucially important for working and long-term memory processing is the hippocampal CA3 region. Whereas learning-facilitated plasticity has been described in this structure, the mechanisms underlying this phenomenon have not been explored. The noradrenergic system plays an important role in arousal and qualification of new information as salient. It regulates synaptic plasticity in the dentate gyrus and CA1, but nothing is known about the regulation by the noradrenergic system of synaptic plasticity in the CA3 region. We explored whether β-adrenergic receptors contribute to learning-facilitated plasticity at mossy fiber (mf)-CA3 synapses of behaving rats. We found that receptor antagonism had no effect on basal synaptic transmission, short-term potentiation (STP), short-term depression, LTP, or LTD, that were electrically induced by patterned afferent stimulation. We found, however, that both learning-facilitated LTP and LTD were prevented by antagonism of β-adrenergic receptors, whereas the agonist isoproterenol facilitated STP into LTP. Thus, learning-facilitated and electrically-induced plasticity may not share the same prerequisites. These results support that the mf synapse engages in a distinct aspect of encoding of spatial information that involves both LTP and LTD. Furthermore, changes in arousal that are coupled to new learning are associated with activation of hippocampal β-adrenergic receptors that in turn comprise a key element in this type of information acquisition and processing by the CA3 region.
Peritoneal Dialysis Underutilization: The Impact of an Interventional Nephrology Peritoneal Dialysis Access Program

Peritoneal dialysis (PD) is an underutilized form of renal replacement therapy. Recent data have emphasized that only 12% of end‐stage renal disease (ESRD) patients are initiated on this form of therapy in the United States. Patients requiring PD have most often been referred to general surgeons for catheter placement. This has incurred additional delays in starting treatment and loss of decision‐making control by the referring nephrologist. To address this issue, we developed and incorporated our own PD access placement program into the preexisting chronic kidney disease (CKD) education program. To date, 46 patients have undergone 71 procedures. These included 51 (72%) PD catheter insertions, 14 (20%) removals, and 6 (8%) repositioning procedures for poor drainage. PD catheter insertion was performed peritoneoscopically under local anesthesia and a Fogarty catheter was used to reposition a migrated catheter. All of the procedures were performed by nephrologists in a dedicated interventional nephrology (IN) laboratory. All six repositioning procedures failed to restore optimal drainage. Five of these patients had the catheter removed and a new catheter placed during the same procedure. Of these five patients, one had recurrence of poor drainage and opted for hemodialysis (HD). The sixth patient declined reinsertion and chose HD. Of the remaining seven removal procedures, three were due to fungal peritonitis, one due to bowel perforation, one due to severe depression, one due to transplant, and one catheter was removed at the request of the primary physician in a terminally ill patient. Eight of the 51 catheter insertions were during the initial admission of a catastrophic dialysis start. Two of these patients started acute PD and avoided catheter placement for HD. Thirty‐seven of 46 patients have a functional PD catheter with a follow‐up of 8.6 ± 0.8 (mean ± SE) months. During an 18‐month period our PD population has increased from 43 to 80 patients. We conclude that a dedicated PD access placement program coupled with a CKD education program can have a dramatic impact on patient choice and PD growth.
The Optimal Density of Infinite Constellations for the Gaussian Channel

The setting of a Gaussian channel without power constraints is considered. In this setting the codewords are points in an n-dimensional Euclidean space (an infinite constellation). The channel coding analog of the number of codewords is the density of the constellation points, and the analog of the communication rate is the normalized log density (NLD). The highest achievable NLD with vanishing error probability (which can be thought of as the capacity) is known, as well as error exponents for the setting. In this work we are interested in t he optimal NLD for communication when a fixed, nonzero error probability is allowed. In classi cal channel coding the gap to capacity is characterized by the channel dispersion (and cannot be derived from error exponent theory). In the unconstrained setting, we show that as the codeword length (dimension) n grows, the gap to the highest achievable NLD is inversely proportional (to the first order) to the square root of the block length. We give an explicit expression for the proportion constant, which is given by the inverse Q-function of the allowed error probability, times the square root of 1 . In an analogy to a similar result in classical channel coding, it follows tha t the dispersion of infinite constellations is given by 1 nat 2 per channel use. We show that this optimal convergence rate can be achieved using lattices, therefore the result holds for the maximal e rror probability as well. Connections to the error exponent of the power constrained Gaussian channel and to the volume-to-noise ratio as a figure of merit are discussed.
Identification of a peroxisomal targeting signal at the carboxy terminus of firefly luciferase

Translocation of proteins across membranes of the endoplasmic reticulum, mitochondrion, and chloroplast has been shown to be mediated by targeting signals present in the transported proteins. To test whether the transport of proteins into peroxisomes is also mediated by a peptide targeting signal, we have studied the firefly luciferase gene that encodes a protein transported to peroxisomes in both insect and mammalian cells. We have identified two regions of luciferase which are necessary for transport of this protein into peroxisomes. We demonstrate that one of these, region II, represents a peroxisomal targeting signal because it is both necessary and sufficient for directing cytosolic proteins to peroxisomes. The signal is no more than twelve amino acids long and is located at the extreme carboxy-terminus of luciferase. The location of the targeting signal for translocation across the peroxisomal membrane therefore differs from the predominantly amino-terminal location of signals responsible for transport across the membranes of the endoplasmic reticulum, chloroplast, or mitochondrion.
Binary division algorithm and high speed deconvolution algorithm (Based on Ancient Indian Vedic Mathematics)

The performance of any processor solely depends upon its power, area and delay. In order to get an effective processor, its power, area and delay should be less. Division is always considered to be bulky and one of the most difficult operations in arithmetic and hence all the implementations of division algorithms in VLSI architecture have higher orders of time and space complexities. Vedic Mathematics on the other hand offers a new holistic approach to mathematics. Its range extends from the most concrete values of numerical computation to the most abstract aspects of the dynamics of intelligence. In this work we have implemented an optimized binary division architecture using sutras of Vedic Mathematics which are Nikhilam Sutra and Parvartya Sutra. This work discusses about these two algorithms of division and their application for calculating deconvolution. Both the algorithms have been implemented with improved results of time delay and are with fewer complexities. The proposed division algorithm is coded in Verilog, synthesized and simulated using Xilinx ISE design suit 14.2. Simulated results for proposed Vedic divider circuit shows a reduction in delay of 19% than the conventional method.
A normalized contrast‐encoding model exhibits bright/dark asymmetries similar to early visual neurons

Biological sensory systems share a number of organizing principles. One such principle is the formation of parallel streams. In the visual system, information about bright and dark features is largely conveyed via two separate streams: the ON and OFF pathways. While brightness and darkness can be considered symmetric and opposite forms of visual contrast, the response properties of cells in the ON and OFF pathways are decidedly asymmetric. Here, we ask whether a simple contrast‐encoding model predicts asymmetries for brights and darks that are similar to the asymmetries found in the ON and OFF pathways. Importantly, this model does not include any explicit differences in how the visual system represents brights and darks, but it does include a common normalization mechanism. The phenomena captured by the model include (1) nonlinear contrast response functions, (2) greater nonlinearities in the responses to darks, and (3) larger responses to dark contrasts. We report a direct, quantitative comparison between these model predictions and previously published electrophysiological measurements from the retina and thalamus (guinea pig and cat, respectively). This work suggests that the simple computation of visual contrast may account for a range of early visual processing nonlinearities. Assessing explicit models of sensory representations is essential for understanding which features of neuronal activity these models can and cannot predict, and for investigating how early computations may reverberate through the sensory pathways.
Drink Driving: The Effects of Enforcement

In a national survey carried out in 1986, 1700 drivers were interviewed about their beliefs, attitudes and behaviour towards drinking and driving. Drawing on analysis of the results of this survey and recent evidence from other countries, this report discusses whether the drink drive problem in England and Wales could be dealt with by raising the levels of enforcement. Analysis of the results of the survey show that drink driving is closely associated with the following five types of factors: 1) whether drivers regarded drinking and driving as important aspects of their social lives; 2) drivers' beliefs about how drinking increased their chances of being stopped by the police and drivers' concern about the legal consequences of conviction; 3) drivers' beliefs about the dangers of drinking before driving; 4) drivers' beliefs about the likelihood that family or friends would disapprove of their drinking and driving, and 5) the experienced effects of alcohol on mood and behaviour. Taken together, the findings of past research and of this survey support a policy of increased enforcement activity. The conclusion drawn is that wider use of the breathalyser in routine traffic law enforcement coupled with an increase in the number of driver check points could, with supporting media coverage, produce major and lasting improvements in road safety and, ultimately, in reducing the number of offenders and their victims. (TRRL)
Efficacy and safety of apixaban compared with warfarin according to age for stroke prevention in atrial fibrillation: observations from the ARISTOTLE trial

Aims The risk of stroke in patients with atrial fibrillation (AF) increases with age. In the ARISTOTLE trial, apixaban when compared with warfarin reduced the rate of stroke, death, and bleeding. We evaluated these outcomes in relation to patient age. Methods and results A total of 18 201 patients with AF and a raised risk of stroke were randomized to warfarin or apixaban 5 mg b.d. with dose reduction to 2.5 mg b.d. or placebo in 831 patients with ≥2 of the following criteria: age ≥80 years, body weight ≤60 kg, or creatinine ≥133 μmol/L. We used Cox models to compare outcomes in relation to patient age during 1.8 years median follow-up. Of the trial population, 30% were <65 years, 39% were 65 to <75, and 31% were ≥75 years. The rates of stroke, all-cause death, and major bleeding were higher in the older age groups (P < 0.001 for all). Apixaban was more effective than warfarin in preventing stroke and reducing mortality across all age groups, and associated with less major bleeding, less total bleeding, and less intracranial haemorrhage regardless of age (P interaction >0.11 for all). Results were also consistent for the 13% of patients ≥80 years. No significant interaction with apixaban dose was found with respect to treatment effect on major outcomes. Conclusion The benefits of apixaban vs. warfarin were consistent in patients with AF regardless of age. Owing to the higher risk at older age, the absolute benefits of apixaban were greater in the elderly.
Cultures and Selves

The study of culture and self casts psychology’s understanding of the self, identity, or agency as central to the analysis and interpretation of behavior and demonstrates that cultures and selves define and build upon each other in an ongoing cycle of mutual constitution. In a selective review of theoretical and empirical work, we define self and what the self does, define culture and how it constitutes the self (and vice versa), define independence and interdependence and determine how they shape psychological functioning, and examine the continuing challenges and controversies in the study of culture and self. We propose that a self is the “me” at the center of experience—a continually developing sense of awareness and agency that guides actions and takes shape as the individual, both brain and body, becomes attuned to various environments. Selves incorporate the patterning of their various environments and thus confer particular and culture-specific form and function to the psychological processes they organize (e.g., attention, perception, cognition, emotion, motivation, interpersonal relationship, group). In turn, as selves engage with their sociocultural contexts, they reinforce and sometimes change the ideas, practices, and institutions of these environments.
Do Consensus Indications for Resection in Branch Duct Intraductal Papillary Mucinous Neoplasm Predict Malignancy? A Study of 147 Patients

BACKGROUND AND AIMS:Recent consensus guidelines suggest that presence of ≥1 of the following is an indication for resection (IR) of branch duct intraductal papillary mucinous neoplasm (IPMN-Br): cyst-related symptoms, main pancreatic duct diameter ≥10 mm, cyst size ≥30 mm, intramural nodules, or cyst fluid cytology suspicious/positive for malignancy. Among a cohort of patients with IPMN-Br we determined if the consensus IR (CIR), presence of multifocal IPMN-Br, or growth of cyst size on follow-up predict malignancy.METHODS:We identified 147 patients with IPMN-Br of whom 66 underwent surgical resection at diagnosis and 81 were followed conservatively, of whom 11 were resected during follow-up. Clinical, imaging, histological, and cyst fluid characteristics from all 147 patients with IPMN-Br were obtained from clinical records and/or by contacting the patients. In all cases, presence of CIR at baseline and during follow-up (N = 66), presence of multifocal cysts (N = 57), and increase in cyst size (N = 38) were noted.RESULTS:Among the 77 resected IPMN-Brs, at initial evaluation 61 had at least one CIR and 16 had none. Malignancy was present in 9/61 (15%) with CIR and 0/16 without IR (P = 0.1). When presence of any one of the CIR was taken as an indicator of malignancy, the CIR had a sensitivity, specificity, positive predictive value, and negative predictive value of 100%, 23%, 14%, and 100%, respectively. Prevalence of malignancy in those with single versus multifocal IPMN-Br was similar (13% vs 11%). No patient has developed malignancy after a median follow-up of 15 months. So far, none of the 38 patients with increase in cyst size on follow-up has developed malignancy related symptoms.CONCLUSIONS:Suggested consensus indications for resection identify all patients with malignancy; however, their specificity is low. In the short term it would be safe to follow patients without these features.
Comparative evaluation of bone–filled Polymethylmethacrylate implant, autograft fusion, and Polyetheretherketone cervical cage fusion for the treatment of single –level cervical disc disease.

Background: The objective of this study is to compare the clinical, functional, and radiological outcomes of using bone-filled Polymethylmethacrylate (PMMA) implant as an inexpensive alternative to Polyetheretherketone (PEEK) cage and Autologous bone graft (ABG) fusion after anterior cervical discectomy (ACD) for the treatment of single level cervical disc disease. Methods: 60 patients were prospectively randomized according to the material used for fusion after ACD into: 1) PMMA implant; 2) ABG; and 3) PEEK implant. The clinical outcomes were evaluated using Visual Analogue Scale (VAS), whereas the functional outcomes were evaluated using Odom's criteria. Radiological evaluations were also conducted using radiography and Computerized tomography (CT) scans and considered the following factors; bony fusion, cervical stability and disc space height (DSH) changes. The post- operative outcomes were evaluated at the following intervals; 2 weeks, 3 and 6 months. Results: The clinical outcomes demonstrated insignificant difference among the three treated groups throughout their follow up period. ABG group showed significant lower satisfactory functional outcomes (68.1%) compared to PMMA and PEEK groups (85% and 88.9%, respectively) at the 2-week post operative evaluation, but the ABG group showed closer functional outcomes to the PMMA and PEEK groups at the 3 and 6-month post operative evaluations. Despite the inferior bony fusion rates of the PMMA group (30%) compared to ABG group (86.3%) and PEEK group (77.7%) at the 6-month post operative evaluation, the clinical and functional outcomes were comparable. Conclusions: Bone-filled PMMA implant is a reliable treatment option; despite its inferior fusion rate at the 6-month postoperative evaluation, it still provides acceptable segmental stability, satisfactory clinical and functional outcomes that are comparable to ABG and PEEK grafting procedures.
Pharmacotherapy of neuropathic pain: which drugs, which treatment algorithms?

Abstract Neuropathic pain (NP) is a significant medical and socioeconomic burden. Epidemiological surveys have indicated that many patients with NP do not receive appropriate treatment for their pain. A number of pharmacological agents have been found to be effective in NP on the basis of randomized controlled trials including, in particular, tricyclic antidepressants, serotonin and norepinephrine reuptake inhibitor antidepressants, pregabalin, gabapentin, opioids, lidocaine patches, and capsaicin high-concentration patches. Evidence-based recommendations for the pharmacotherapy of NP have recently been updated. However, meta-analyses indicate that only a minority of patients with NP have an adequate response to drug therapy. Several reasons may account for these findings, including a modest efficacy of the active drugs, a high placebo response, the heterogeneity of diagnostic criteria for NP, and an inadequate classification of patients in clinical trials. Improving the current way of conducting clinical trials in NP could contribute to reduce therapeutic failures and may have an impact on future therapeutic algorithms.
Crystal structure and mechanism of action of the xanthine oxidase-related aldehyde oxidoreductase from Desulfovibrio gigas.

The crystal structure of the aldehyde oxidoreductase (Mop) from the sulphate-reducing bacterium Destdjovibrio gigas has been analysed and refined to 1.8A (0.18 nm) resolution in its native ‘desulpho’ form, as well as in ‘resulphurated’, oxidized, reduced and alcohol-bound forms [1,2], allowing a detailed look at several structural aspects relevant to catalysis. In analogy with eukaryotic xanthine oxidases, xanthine dehydrogenases and aldehyde oxidases, Mop is a homodimer of two 100 kDa subunits (2 x907 amino acids) [3] and it contains, per subunit, a molybdopterin cytosine dinucleotide (MCD) cofactor as well as two different kinds of [2Fe-2S] clusters [4], but lacks the flavin and its domain which is present in most molybdenum hydroxylases. It represents the first structure of a member of the xanthine oxidase family of enzymes, with the redox-active cofactors found in discrete domains within a single polypeptide chain. The molecule is roughly globular with an approximate diameter of 75 A and folds into four distinct domains (Fe/S-a, Fe/S-b, Mol and Mo2): the first two (Fe/S-a and Fe/S-b) bind the two iron-sulphur clusters, whereas the larger domains (Mol and Mo2) bind the MCD cofactor in extended conformation by a network of hydrogen-bonding interactions: Mol contributes with two single molybdopterin-binding segments and Mo2 binds the other side of the pterin system