Miracle-dz/UniFAR-FTUs huggingface dataset:
Interpreting treatment effects from clinical trials in the context of real-world risk information: end-stage renal disease prevention in older adults.

IMPORTANCE Older adults are often excluded from clinical trials. The benefit of preventive interventions tested in younger trial populations may be reduced when applied to older adults in the clinical setting if they are less likely to survive long enough to experience those outcomes targeted by the intervention. OBJECTIVE To extrapolate a treatment effect similar to those reported in major randomized clinical trials of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers for prevention of end-stage renal disease (ESRD) to a real-world population of older patients with chronic kidney disease. DESIGN, SETTING, AND PARTICIPANTS Simulation study in a retrospective cohort conducted in Department of Veterans Affairs medical centers. We included 371 470 patients 70 years or older with chronic kidney disease. EXPOSURE Level of estimated glomerular filtration rate (eGFR) and proteinuria. MAIN OUTCOMES AND MEASURES Among members of this cohort, we evaluated the expected effect of a 30% reduction in relative risk on the number needed to treat (NNT) to prevent 1 case of ESRD over a 3-year period. These limits were selected to mimic the treatment effect achieved in major trials of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers for prevention of ESRD. These trials have reported relative risk reductions of 23% to 56% during observation periods of 2.6 to 3.4 years, yielding NNTs to prevent 1 case of ESRD of 9 to 25. RESULTS The NNT to prevent 1 case of ESRD among members of this cohort ranged from 16 in patients with the highest baseline risk (eGFR of 15-29 mL/min/1.73 m(2) with a dipstick proteinuria measurement of ≥ 2+) to 2500 for those with the lowest baseline risk (eGFR of 45-59 mL/min/1.73 m(2) with negative or trace proteinuria and eGFR of ≥ 60 mL/min/1.73 m2 with dipstick proteinuria measurement of 1+). Most patients belonged to groups with an NNT of more than 100, even when the exposure time was extended over 10 years and in all sensitivity analyses. CONCLUSIONS AND RELEVANCE Differences in baseline risk and life expectancy between trial subjects and real-world populations of older adults with CKD may reduce the marginal benefit to individual patients of interventions to prevent ESRD.
Yield of culture of Mycobacterium tuberculosis complex in sputum samples transported from tribal areas.

BACKGROUND There is little information on the recovery of Mycobacterium tuberculosis complex from sputum samples collected in the field for bacteriological examination. SETTING Tribal areas in the State of Madhya Pradesh, in central India. METHODS Sputum specimens collected from subjects with chest symptoms in a disease prevalence survey were refrigerated until transportation to the laboratory. The specimens were processed for microscopy and culture. The samples were grouped based on the delay in processing for culture from the day of collection into three groups: 0-3, 4-7 and ≥8 days, and the recovery of M. tuberculosis complex in these groups was analysed. The statistical analysis was performed using χ(2) test. RESULTS Of the 3651 processed specimens, 114 were positive for M. tuberculosis complex by culture and 96 by smear microscopy. The differences in the proportion of 'smear-positive, culture-positive', 'smear-positive, culture-negative' and 'smear-negative, culture-positive' samples between the three groups were not significant. CONCLUSION In difficult-to-reach areas with limited resources, refrigeration of sputum specimens until they are transported for processing at a reference laboratory for culture seems not to significantly affect the recovery of M. tuberculosis complex isolates.
Ambit: In-Memory Accelerator for Bulk Bitwise Operations Using Commodity DRAM Technology

Many important applications trigger bulk bitwise operations, i.e., bitwise operations on large bit vectors. In fact, recent works design techniques that exploit fast bulk bitwise operations to accelerate databases (bitmap indices, BitWeaving) and web search (BitFunnel). Unfortunately, in existing architectures, the throughput of bulk bitwise operations is limited by the memory bandwidth available to the processing unit (e.g., CPU, GPU, FPGA, processing-in-memory). To overcome this bottleneck, we propose Ambit, an Accelerator-in-Memory for bulk bitwise operations. Unlike prior works, Ambit exploits the analog operation of DRAM technology to perform bitwise operations completely inside DRAM, thereby exploiting the full internal DRAM bandwidth. Ambit consists of two components. First, simultaneous activation of three DRAM rows that share the same set of sense amplifiers enables the system to perform bitwise AND and OR operations. Second, with modest changes to the sense amplifier, the system can use the inverters present inside the sense amplifier to perform bitwise NOT operations. With these two components, Ambit can perform any bulk bitwise operation efficiently inside DRAM. Ambit largely exploits existing DRAM structure, and hence incurs low cost on top of commodity DRAM designs (1% of DRAM chip area). Importantly, Ambit uses the modern DRAM interface without any changes, and therefore it can be directly plugged onto the memory bus.Our extensive circuit simulations show that Ambit works as expected even in the presence of significant process variation. Averaged across seven bulk bitwise operations, Ambit improves performance by 32X and reduces energy consumption by 35X compared to state-of-the-art systems. When integrated with Hybrid Memory Cube (HMC), a 3D-stacked DRAM with a logic layer, Ambit improves performance of bulk bitwise operations by 9.7X compared to processing in the logic layer of the HMC. Ambit improves the performance of three real-world data-intensive applications, 1) database bitmap indices, 2) BitWeaving, a technique to accelerate database scans, and 3) bit-vector-based implementation of sets, by 3X-7X compared to a state-of-the-art baseline using SIMD optimizations. We describe four other applications that can benefit from Ambit, including a recent technique proposed to speed up web search. We believe that large performance and energy improvements provided by Ambit can enable other applications to use bulk bitwise operations.CCS CONCEPTS• Computer systems organization → Single instruction, multiple data; • Hardware → Hardware accelerator; • Hardware → Dynamic memory;
Pediatric craniopharyngiomas: classification and treatment according to the degree of hypothalamic involvement.

OBJECT The current treatment of craniopharyngiomas is evolving into one of a multimodal approach in which the aim is disease control and improved preservation of quality of life (QOL). To date, an appropriate classification system with which to individualize treatment is absent. The objectives of this study were to identify preoperative prognostic factors in patients with craniopharyngiomas and to develop a risk-based treatment algorithm. METHODS The authors reviewed data obtained in a retrospective cohort of 66 children (mean age 7.4 years, mean follow-up period 7 years) who underwent resection between 1984 and 2001. Postoperative recurrence rates, vision status, and endocrine function were consistent with those reported in the literature. The postoperative morbidity was related to hypothalamic dysfunction. The preoperative magnetic resonance imaging grade, clinically assessed hypothalamic function, and the sugeon's operative experience (p = 0.007, p = 0.047, p = 0.035, respectively) significantly predicted poor outcome. Preoperative hypothalamic grading was used in a prospective cohort of 22 children (mean age 8 years, mean follow-up period 1.2 years) treated between 2002 and 2004 to stratify patients according to whether they underwent gross-total resection (GTR) (20%), complete resection avoiding the hypothalamus (40%), or subtotal resection (STR) (40%). In cases in which residual disease was present, the patient underwent radiotherapy. There have been no new cases of postoperative hyperphagia, morbid obesity, or behavioral dysfunction in this prospective cohort. CONCLUSIONS For many children with craniopharyngiomas, the cost of resection is hypothalamic dysfunction and a poor QOL. By using a preoperative classification system to grade hypothalamic involvement and stratify treatment, the authors were able to minimize devastating morbidity. This was achieved by identifying subgroups in which complete resection or STR, performed by an experienced craniopharyngioma surgeon and with postoperative radiotherapy when necessary, yielded better overall results than the traditional GTR.
Effects of trauma on bipolar disorder: the mediational role of interpersonal difficulties and alcohol dependence.

OBJECTIVES This study examined: (i) the prevalence of trauma in a bipolar disorder (BD) sample, and (ii) how trauma histories mediated by interpersonal difficulties and alcohol dependence impact on the severity of BD. The prevalence of posttraumatic stress disorder (PTSD) and its relationship to outcomes in BD were also examined. METHODS Sixty participants were recruited from a geographically well-defined mental health service in Northern Ireland. Self-reported trauma histories, PTSD, interpersonal difficulties and alcohol dependence and were examined in relation to illness severity. RESULTS A high prevalence of trauma was found. Trauma predicted the frequency of hospital admissions (R(2) = 0.08), quality of life (R(2) = 0.23) and inter-episode depressive symptoms (R(2) = 0.13). Interpersonal difficulties, but not alcohol dependence, appeared to play an important role in mediating these adverse effects. While only 8% of the sample met criteria for active PTSD, this comorbid disorder was associated with BD severity. CONCLUSIONS This study indicates that awareness of trauma is important in understanding individual differences in bipolar presentations. The theoretical and clinical implications of evidence that trauma is related to more adverse outcomes in BD are discussed. The finding that interpersonal difficulties mediate the relationship between trauma and BD severity is novel. The need for adjunctive evidence-based treatments targeting interpersonal difficulties is considered.
Signal Transduction from N-cadherin Increases Bcl-2

Associated with the metastatic progression of epithelial tumors is the dynamic regulation of cadherins. Whereas E-cadherin is expressed in most epithelium and carcinomas, recent studies suggest that the up-regulation of other cadherin subtypes in carcinomas, such as N-cadherin, may function in cancer progression. We demonstrate that a signal transduction cascade links the N-cadherin·catenin adhesion complex to up-regulation of the anti-apoptotic protein Bcl-2. In suspension, aggregates of DU-145 cells, an E-cadherin expressing human prostate carcinoma line, survive loss of integrin-dependent adhesion by a different anti-apoptotic signaling pathway than the N-cadherin expressing lines PC3 and PC3N. N-cadherin intercellular adhesion mediates a 3.5-fold increase in Bcl-2 protein expression, whereas the level of the proapoptotic protein Bax remains constant. Only N-cadherin ligation in PC3 cells, which express both N-cadherin and E-cadherin, is sufficient to induce activation of Akt/protein kinase B. N-cadherin homophilic ligation initiates phosphatidylinositol 3-kinase-dependent activation of Akt resulting in Akt phosphorylation of Bad on serine 136. Following N-cadherin homophilic adhesion phosphatidylinositol 3-kinase was identified in immunoprecipitates of the N-cadherin·catenin complex. The recruitment of phosphatidylinositol 3-kinase to the adhesion complex is dependent on ligation of N-cadherin and an organized actin cytoskeleton because cytochalasin D blocks the recruitment. We propose that N-cadherin homophilic adhesion can initiate anti-apoptotic signaling, which enhances the Akt cell survival pathway in metastatic cancer.
Acetylcholine-Synthesizing T Cells Relay Neural Signals in a Vagus Nerve Circuit

A neural circuit that involves a specialized population of memory T cells regulates the immune response. Neural circuits regulate cytokine production to prevent potentially damaging inflammation. A prototypical vagus nerve circuit, the inflammatory reflex, inhibits tumor necrosis factor–α production in spleen by a mechanism requiring acetylcholine signaling through the α7 nicotinic acetylcholine receptor expressed on cytokine-producing macrophages. Nerve fibers in spleen lack the enzymatic machinery necessary for acetylcholine production; therefore, how does this neural circuit terminate in cholinergic signaling? We identified an acetylcholine-producing, memory phenotype T cell population in mice that is integral to the inflammatory reflex. These acetylcholine-producing T cells are required for inhibition of cytokine production by vagus nerve stimulation. Thus, action potentials originating in the vagus nerve regulate T cells, which in turn produce the neurotransmitter, acetylcholine, required to control innate immune responses.
Design elements of new classes of quasi-orthogonal spreading codes for tactical soft frequency hopping radios networks operation in multiple access and tone jamming environment

The paper presents an approach to place the design of spreading codes (SC) for tactical soft frequency hopping radios networks in an environment linking multiple access interference (MAI) and tone jamming, using Galois extended field-GF(pn) oriented basics elements for an optimal design of the new classes of quasi orthogonal (QO)-SC (providing single frequency overlap as MAI). The paper includes applications results which confirm the necessity and advantages to develop QO-SC.
Tumor vasculogenic mimicry formation as an unfavorable prognostic indicator in patients with breast cancer

Vasculogenic mimicry (VM), a newly defined pattern of tumor blood perfusion, describes the functional plasticity of aggressive tumor cells forming de novo vascular networks and is associated with the cancer progression and metastasis. However, the VM-positive rate and the impact of VM status on breast cancer patients’ clinicopathological parameters and prognosis remain unclear. Thus, we performed a meta-analysis by incorporating all available evidence to clarify these issues. Eight studies that involved 1,238 breast cancer patients were eligible for inclusion in our study. We found the VM-positive rate was 24% (pooled proportion was 0.24, 95% CI= 0.13–0.34), and VM was significantly associated with larger tumor size (>2 cm) (OR=0.49, 95% CI=0.26-0.90, P=0.02) and lymph node metastasis (OR=0.27, 95% CI=0.13-0.57, P=0.0005). A boardline correlation was also identified between VM and poorer differentiation (Grade II-III) (OR=0.07, 95% CI=0.00-1.24, P=0.07). Nevertheless, no statistically significant associations were observed between VM and hormone receptor and human epidermal growth factor receptor 2 status. Moreover, the results showed that breast cancer patients with VM-positive have a shorter overall survival than those with VM-negative (HR=0.23, 95% CI=0.08-0.38,P=0.003). In summary, VM was associated with more aggressive tumor phenotype and poor prognosis in patients with breast cancer. Developing strategies against the VM formation would be a promising therapeutic approach to breast cancer.
Infectious and parasitic diseases of captive carnivores, with special emphasis on the black-footed ferret (Mustela nigripes).

Captive carnivores are susceptible to a wide array of infectious and parasitic diseases, which reflects the diversity of the seven families of Carnivora. Unfortunately, relatively few in-depth studies have been conducted on diseases of non-domestic carnivores, and much remains to be learned, especially regarding diseases of small carnivores (e.g. mustelids, viverrids and procyonids). The more important infectious diseases of carnivores include rabies, canine distemper, and diseases caused by parvoviruses, coronaviruses and herpesviruses. Few parasitic or bacterial pathogens are significant in captive populations, and appropriate husbandry, therapy, vaccines and quarantine minimize the risk of disease. Extrapolations from one species to another regarding disease susceptibility may be incorrect. The black-footed ferret (Mustela nigripes) serves as an example of a carnivore significantly affected by infectious diseases, some of which were expected while others could not have been predicted from generalized knowledge of diseases of mustelids. This highlights the need to understand the natural history of each species maintained in captivity.
Mutations in the second C2 domain of synaptotagmin disrupt synaptic transmission at Drosophila neuromuscular junctions

The synaptic vesicle protein, synaptotagmin, has been hypothesized to mediate several functions in neurotransmitter release including calcium sensing, vesicle recycling, and synaptic vesicle docking. These hypotheses are based on evidence from in vitro binding assays, peptide and antibody injection experiments, and genetic knockout studies. Synaptotagmin contains two domains that are homologous to the calcium ion (Ca2+)‐binding C2 domain of protein kinase C. The two C2 domains of synaptotagmin have broadly differing ligand‐binding properties. We have focused on the second C2 domain (C2B) of synaptotagmin I, in particular, on a series of conserved lysine residues on β‐strand 4 of C2B. This polylysine motif binds clathrin‐adapter protein AP‐2, neuronal calcium channels, and inositol high polyphosphates. It also mediates Ca2+‐dependent oligomerization. To investigate the importance of these lysine residues in synaptic transmission, we have introduced synaptotagmin I (syt) transgenes harboring specific polylysine motif mutations into flies otherwise lacking the synaptotagmin I protein (sytnull). Electrophysiological analyses of these mutants revealed that evoked transmitter release is decreased by ≈36% and that spontaneous release is increased approximately twofold relative to sytnull flies that express a wild type syt transgene. Synaptotagmin expression in both the mutant and the wild type transgenic lines was equivalent, as measured by semiquantitative Western blot analysis. Thus, the alteration in synaptic transmission was due to the mutation and not to the level of synaptotagmin expression. We conclude that synaptotagmin interactions mediated by the C2B polylysine motif are required to attain full synaptotagmin function in vivo. J. Comp. Neurol. 436:4–16, 2001. © 2001 Wiley‐Liss, Inc.
In vitro tests of substitute lubricants for wear testing orthopaedic biomaterials

Bovine serum is the lubricant recommended by several international standards for the wear testing of orthopaedic biomaterials; however, there are issues over its use due to batch variation, degradation, cost and safety. For these reasons, alternative lubricants were investigated. A 50-station Super-CTPOD (circularly translating pin-on-disc) wear test rig was used, which applied multidirectional motion to ultra-high-molecular-weight polyethylene test pins rubbing against cobalt chromium discs. Thirteen possible alternative lubricants were tested. The use of soy protein as a lubricant gave statistically higher wear, while soya oil, olive oil, Channel Island milk, whole milk, whey, wheatgerm oil, 11 mg/mL egg white, albumin/globulin mix and albumin/globulin/chondroitin sulphate mix all gave statistically lower wear than bovine serum. The lubricants giving the closest wear results to bovine serum were 20 and 40 mg/mL egg white solutions. A light absorbance assay found that these egg white solutions suffered from a high degradation rate that increased with increasing protein content. While egg white solutions offer the best alternative lubricant to bovine serum due to the wear volumes produced, cost-effectiveness and safety of handling, protein degradation will still occur, leading to the need for regular lubricant replacement. Of the lubricants tested in this study, none were found to be superior to bovine serum.
In vitro characterization of an internal ribosomal entry site (IRES) present within the 5' nontranslated region of hepatitis A virus RNA: comparison with the IRES of encephalomyocarditis virus

The lengthy 5' nontranslated region (5'NTR) of hepatitis A virus (HAV) forms a highly ordered secondary structure, which has been suggested to play an important role in controlling viral translation by allowing for translation initiation by internal ribosome entry. To test this hypothesis, synthetic bicistronic RNAs, with all or part of the HAV 5'NTR in the intercistronic space, were translated in rabbit reticulocyte lysates. In the presence of an upstream cistron designed to block ribosomal scanning, the HAV 5'NTR was capable of directing the internal initiation of translation, confirming the presence of an internal ribosome entry site (IRES). Analysis of various deletion mutants demonstrated that the 5' border of the IRES is located between nucleotides 151 and 257, while the 3' border extends to the 3' end of the 5'NTR, between nucleotide 695 and the first initiation codon at 735. Except for a segment between bases 638 and 694, deletion of stem-loop structures between bases 151 and the 3' end of the 5'NTR inhibited or abolished translation. The addition of a 5' cap structure (m7GpppN) to monocistronic or bicistronic transcripts decreased the translation of a reporter gene downstream of the HAV 5'NTR but enhanced translation of the upstream cistron in bicistronic transcripts. This finding indicates that a 5' cap structure is inhibitory to HAV IRES-directed translation initiation and that the cap structure and the HAV IRES probably compete for the same limiting translation factors. The efficiency with which monocistronic constructs containing the HAV 5'NTR directed translation in reticulocyte lysates was compared with results for monocistronic constructs containing the IRES of the more rapidly growing encephalomyocarditis virus (EMCV). These results indicated that the HAV 5'NTR was more than 25-fold less active than the EMCV IRES in producing translation product. HAV 5'NTR-directed translation was inhibited by the presence of a one-fifth molar quantity of RNA containing the EMCV IRES, while a fivefold molar excess of the HAV 5'NTR did not inhibit EMCV IRES-directed translation. The relatively weak activity of the HAV IRES may thus be due to a reduced affinity for cellular translation factors which are present in limiting quantities in rabbit reticulocyte lysate.
A Single Amino Acid Tunes Ca2+ Inhibition of Brain Liver Intestine Na+ Channel (BLINaC)

Ion channels of the degenerin/epithelial Na+ channel gene family are Na+ channels that are blocked by the diuretic amiloride and are implicated in several human diseases. The brain liver intestine Na+ channel (BLINaC) is an ion channel of the degenerin/epithelial Na+ channel gene family with unknown function. In rodents, it is expressed mainly in brain, liver, and intestine, and to a lesser extent in kidney and lung. Expression of rat BLINaC (rBLINaC) in Xenopus oocytes leads to small unselective currents that are only weakly sensitive to amiloride. Here, we show that rBLINaC is inhibited by micromolar concentrations of extracellular Ca2+. Removal of Ca2+ leads to robust currents and increases Na+ selectivity of the ion pore. Strikingly, the species ortholog from mouse (mBLINaC) has an almost 250-fold lower Ca2+ affinity than rBLINaC, rendering mBLINaC constitutively active at physiological concentrations of extracellular Ca2+. In addition, mBLINaC is more selective for Na+ and has a 700-fold higher amiloride affinity than rBLINaC. We show that a single amino acid in the extracellular domain determines these profound species differences. Collectively, our results suggest that rBLINaC is opened by an unknown ligand whereas mBLINaC is a constitutively open epithelial Na+ channel.