Miracle-dz/UniFAR-FTUs huggingface dataset:
A Hybrid Feature Subset Selection Algorithm for Analysis of High Correlation Proteomic Data

Pathological changes within an organ can be reflected as proteomic patterns in biological fluids such as plasma, serum, and urine. The surface-enhanced laser desorption and ionization time-of-flight mass spectrometry (SELDI-TOF MS) has been used to generate proteomic profiles from biological fluids. Mass spectrometry yields redundant noisy data that the most data points are irrelevant features for differentiating between cancer and normal cases. In this paper, we have proposed a hybrid feature subset selection algorithm based on maximum-discrimination and minimum-correlation coupled with peak scoring criteria. Our algorithm has been applied to two independent SELDI-TOF MS datasets of ovarian cancer obtained from the NCI-FDA clinical proteomics databank. The proposed algorithm has used to extract a set of proteins as potential biomarkers in each dataset. We applied the linear discriminate analysis to identify the important biomarkers. The selected biomarkers have been able to successfully diagnose the ovarian cancer patients from the noncancer control group with an accuracy of 100%, a sensitivity of 100%, and a specificity of 100% in the two datasets. The hybrid algorithm has the advantage that increases reproducibility of selected biomarkers and able to find a small set of proteins with high discrimination power.
Evaluation of the generation of genotoxic and cytotoxic metabolites of benzo[a]pyrene, aflatoxin B1, naphthalene and tamoxifen using human liver microsomes and human lymphocytes

1 The ability of model stable epoxides and metabolites generated by human liver microsomes from benzo[a]pyrene, aflatoxin B1, naphthalene and tamoxifen to produce cytotoxicity and genotoxicity in human periph eral lymphocytes has been investigated. 2 The stable epoxides 1,1,1 trichloropropene-2,3-oxide (100μM) and trans stilbene oxide (100μM) as well as metabolites generated from aflatoxin B1 (30μM) and naph thalene (100μM) by an extracellular metabolising system were toxic to isolated resting mononuclear leucocytes (MNLs), whereas glycidol (100μM), benzo[a]pyrene (100μM) and tamoxifen (50μM) were not. 3 The stable epoxides 1,1,1 trichloropropene-2,3-oxide (100μM) and trans stilbene oxide (100μM) but not glycidol (100μM) were toxic to dividing lymphocytes only after a 72-h exposure. Tamoxifen (30μM), aflatoxin B 1 (30μM) and their metabolites were also toxic to dividing lymphocytes. Benzo[a]pyrene (100μM) and naphthalene (100/μM) were not toxic either in the absence or presence of the extracel lular metabolising system. 4 Benzo[a]pyrene (100/μM) and aflatoxin B1 (30μM) were directly genotoxic to lymphocytes, this genotoxicity was significantly enhanced by the presence of the extracellular metabolising system. This indicates that both intracellular and extracellular bioactivation of these two compounds can produce genotoxicity. In contrast, naphthalene and tamoxifen were non-genotoxic.
Positively charged synthetic peptides from structural proteins of papillomaviruses abrogate human papillomavirus infectivity

Human papillomavirus (HPV) virus‐like particles (VLP) and synthetic peptides corresponding to positively‐charged sequences of the major and minor capsid proteins were tested for their efficacy in inhibiting the infectivity of HPV 31 pseudovirions by blocking virus entry into cells. A greater than 80% reduction of transfection was observed with one HPV‐31 peptide at a concentration of 10 μg/ml. Moreover, the blocking was not type‐specific since similar reduction in transfection was observed with peptides from other HPV types at a concentration of 60 μg/ml. This concentration was non‐toxic for the cells. These findings indicate that some of the positively‐charged sequences of the L1 and L2 HPV capsid proteins of papillomavirus are compounds that might be locally active against sexually transmitted papillomavirus. The findings provide further evidence that cellular glycosamino‐glycans (GAGs) are functional receptors for HPVs. J. Med. Virol. 73:474–480, 2004. © 2004 Wiley‐Liss, Inc.
Intrathecal Gabapentin Enhances the Analgesic Effects of Subtherapeutic Dose Morphine in a Rat Experimental Pancreatitis Model

Background: Morphine sulfate has long been used for analgesia, but clinical applications can be limited by side effects, tolerance, and potential for addiction at therapeutic doses. An agent that produces therapeutic analgesia when coadministered with low-dose morphine could have important clinical uses. The anticonvulsant agent gabapentin has been identified as having antihyperalgesic properties acting on the &agr;2&dgr;1 subunit of N-type voltage-activated calcium channels on dorsal root ganglia neurons. In this study, intrathecal gabapentin, which by itself is ineffective when administered spinally, was combined with low-dose morphine and tested in an acute bradykinin-induced pancreatitis model in rats. Methods: An intrathecal catheter was surgically inserted into the subarachnoid space of male Sprague-Dawley rats. A laparotomy was performed for ligation and cannulation of the bile-pancreatic duct. Rats were pretreated intrathecally with artificial cerebrospinal fluid, gabapentin, morphine, or combined gabapentin and morphine 30 min before bradykinin injection into the bile-pancreatic duct. Spontaneous behavioral activity (cage crossing, rearing, and hind limb extension) was monitored before drug injection (baseline) and after bradykinin injection into the bile-pancreatic duct to assess visceral pain. Results: Spinal pretreatment with up to 300 &mgr;g gabapentin alone was not effective in reducing hind limb extension in this model, but did restore some cage crossing and rearing behaviors. Spinal treatment with low-dose morphine reduced hind limb extension only. Spinal pretreatment with combined gabapentin and subtherapeutic doses of morphine sulfate resulted in restoration of all spontaneous behaviors to surgical baseline levels including elimination of hind limb extension. Conclusion: Combined spinal administration of gabapentin and low doses of morphine significantly reduces pain-related behaviors in this acute rat pancreatitis model, whereas these agents were ineffective when used alone in this dose range. These data suggest that the &agr;2&dgr;1 subunit of the N-type voltage-activated Ca2+ channels is involved in transmission of this visceral pain, likely through effects on primary afferent endings in the spinal cord. Thus, gabapentin may be an effective adjuvant to initial low dose spinal opioid therapy for clinical management of visceral pain.
Response of Colorado River runoff to dust radiative forcing in snow

The waters of the Colorado River serve 27 million people in seven states and two countries but are overallocated by more than 10% of the river’s historical mean. Climate models project runoff losses of 7–20% from the basin in this century due to human-induced climate change. Recent work has shown however that by the late 1800s, decades prior to allocation of the river’s runoff in the 1920s, a fivefold increase in dust loading from anthropogenically disturbed soils in the southwest United States was already decreasing snow albedo and shortening the duration of snow cover by several weeks. The degree to which this increase in radiative forcing by dust in snow has affected timing and magnitude of runoff from the Upper Colorado River Basin (UCRB) is unknown. Here we use the Variable Infiltration Capacity model with postdisturbance and predisturbance impacts of dust on albedo to estimate the impact on runoff from the UCRB across 1916–2003. We find that peak runoff at Lees Ferry, Arizona has occurred on average 3 wk earlier under heavier dust loading and that increases in evapotranspiration from earlier exposure of vegetation and soils decreases annual runoff by more than 1.0 billion cubic meters or ∼5% of the annual average. The potential to reduce dust loading through surface stabilization in the deserts and restore more persistent snow cover, slow runoff, and increase water resources in the UCRB may represent an important mitigation opportunity to reduce system management tensions and regional impacts of climate change.
Interindividual variability and co-regulation of DNA methylation differ among blood cell populations

DNA methylation regulates gene expression in a cell-type specific way. Although peripheral blood mononuclear cells (PBMCs) comprise a heterogeneous cell population, most studies of DNA methylation in blood are performed on total mononuclear cells. In this study, we investigated high resolution methylation profiles of 58 CpG sites dispersed over eight immune response genes in multiple purified blood cells from healthy adults and newborns. Adjacent CpG sites showed methylation levels that were increasingly correlated in adult blood vs. cord blood. Thus, while interindividual variability increases from newborn to adult blood, the underlying methylation changes may not be merely stochastic, but seem to be orchestrated as clusters of adjacent CpG sites. Multiple linear regression analysis showed that interindividual methylation variability was influenced by distance of average methylation levels to the closest border (0 or 100%), presence of transcription factor binding sites, CpG conservation across species and age. Furthermore, CD4+ and CD14+ cell types were negative predictors of methylation variability. Concerns that PBMC methylation differences may be confounded by variations in blood cell composition were justified for CpG sites with large methylation differences across cell types, such as in the IFN-γ gene promoter. Taken together, our data suggest that unsorted mononuclear cells are reasonable surrogates of CD8+ and, to a lesser extent, CD4+ T cell methylation in adult peripheral, but not in neonatal, cord blood.
Stimulation of Hypoxia-Inducible Factor-1 Alpha (HIF-1α) Protein in the Adult Rat Testis Following Ischemic Injury Occurs Without an Increase in HIF-1α Messenger RNA Expression1

Abstract Hypoxia-inducible factor 1 (HIF-1) is a transcription factor composed of α and β subunits. Stabilized from proteasome degradation and activated by hypoxia, HIF-1 stimulates expression of hypoxia-sensitive genes that mediate oxygen homeostasis in many tissues. Our hypothesis is that HIF-1 is involved in the cellular response to hypoxia in the ischemic testis. Goals of this study were to determine if HIF-1α mRNA is expressed in the testis, epididymis, and accessory sex glands of adult Sprague-Dawley rats and to determine if HIF-1α mRNA and protein expression in the testis is affected by experimentally induced ischemia. Total RNA from reproductive organs of adult rats was analyzed by relative reverse transcription-polymerase chain reaction (RT-PCR) analysis. HIF-1α mRNA showed equal expression in testis, all segments of epididymis, ductus deferens, accessory sex glands, and penis. To examine the effects of ischemia on HIF-1α mRNA and protein expression in the testis, rats were subjected to unilateral testicular ischemia by placing a ligature around spermatic artery or ischemia-inducing experimental torsion and reperfusion. RT-PCR revealed that HIF-1α mRNA expression at all times of ischemic treatment and reperfusion was unchanged compared with normoxic controls. HIF-1α protein was detected by immunoblot analysis of nuclear protein extracts from normoxic testes. Steady-state levels of HIF-1α protein were stimulated by 15 min of ischemia and showed a 2-fold increase at 30 min and 1, 3, and 6 h. HIF-1α protein was also elevated by experimental torsion and reperfusion compared with normoxic controls. These results support the hypothesis that HIF-1 may play a role in the cellular response to hypoxia in the ischemic testis.
Shoulder kinetics during start-up and propulsion with a manual wheelchair within the initial phase of uninstructed training

Abstract Purpose: Wheelchair locomotion is constraining for the upper limbs and involves a set of motor tasks that need to be learnt by a novice user. To understand this integration process, we investigated the evolution of shoulder kinetics during start-up and propulsion within the initial phase of low-intensity uninstructed training. Materials and methods: Seventeen novice able-bodied subjects performed a 120-min uninstructed practice distributed over 4 weeks. During the initial and final sessions, upper limbs kinematics and hand-rim kinetics were continuously collected. Inverse kinematics and dynamics coupled to a three-dimensional linked-segment model were used to compute shoulder net moments. Results: Participants increased the speed of the wheelchair with practice. In average, an increase of shoulder net moments and mechanical work during the push phase was observed. Conversely, during the recovery phase, participants slightly increased shoulder power but maintained a similar level of shoulder loading. However, individual evolutions allowed the definition of two groups defined as: “increasers”, who increased shoulder loading and mechanical work versus “decreasers”, who managed to limit shoulder loading while improving the wheelchair speed. Conclusion: These findings underline that individual adaptation strategies are essential to take into account when designing a rehabilitation protocol for wheelchair users. Implications for Rehabilitation The learning process of manual wheelchair locomotion is essential for the assimilation of motor tasks leading individuals to select their propulsion technique. Novice users display different learning strategies: some people increase shoulder loading very early but others spontaneously manage to increase the wheelchair speed while maintaining a constant level of shoulder loading. Wheelchair rehabilitation programs should be individualized to take into account the subject-specific learning strategy.
Homocysteine, Cystatin C and N-Terminal-Pro Brain Natriuretic Peptide

Background: There is increasing evidence that vascular disease contributes to cognitive impairment and dementia. Clarification of the role of vascular risk factors in dementia is important because most are modifiable, in contrast to other risk factors such as age and genetics. Methods: In 451 patients with mental illness we have investigated three biochemical markers related to vascular disease, total plasma homocysteine (tHcy), cystatin C, and N-terminal-pro brain natriuretic peptide (NT-proBNP), and their association with vascular disease, diagnoses, and brain imaging findings (CT). Results: Plasma tHcy, serum cystatin C, and serum NT-proBNP showed significantly increased frequencies of elevated levels in patients with vascular disease, in patients with a pathological CT finding indicating cerebrovascular disease, and in patients above 75 years of age. Conclusion: It is possible that the control of conventional vascular risk factors and therapy could be guided by the level of plasma tHcy, serum cystatin C, and serum NT-proBNP. Patients with an elevation of any of these three parameters could be selected for a lower target level of risk factors such as blood pressure, hyperlipidemia etc. than conventional target levels.
Ondansetron prevents postoperative emesis in male outpatients. S3A-379 Study Group.

STUDY OBJECTIVES To determine (1) the efficacy and safety of ondansetron in the prevention of postoperative nausea and vomiting (PONV) in male outpatients; (2) prognostic factors for PONV in male outpatients; and (3) patients' perceptions of the debilitating effects of PONV in the ambulatory surgery setting. DESIGN Prospective, randomized, stratified, double-blind study. SETTING Multicenter-24 medical centers. PATIENTS 468 ASA physical status I and II males at least 12 years of age scheduled for general anesthesia. INTERVENTIONS All patients received intravenous ondansetron 4 mg or placebo prior to undergoing general balanced (opioid) anesthesia. MEASUREMENTS AND MAIN RESULTS In the postanesthesia care unit (PACU), the number of emetic episodes, vital signs, adverse events, and nausea assessments were recorded by a blinded observer. After discharge, and until the end of the 24-hour study period, patients completed a diary that collected emetic episodes, adverse events, nausea, and pharmacoeconomic data. There were no differences in patient demographics or safety profiles between groups. The number of patients with no emesis and no nausea during the 24-hour study period was significantly greater (p < 0.05) with ondansetron 4 mg compared with placebo. Prognostic factors for an increased likelihood of developing PONV in males included a history of motion sickness or previous PONV, patients undergoing nonorthopedic procedures, and surgeries lasting longer than one hour. Finally, 38% of patients experiencing PONV perceived PONV to be as, or more debilitating than, the aftereffects of surgery itself. CONCLUSIONS Ondansetron 4 mg was more effective than placebo in preventing PONV in male outpatients. Males at potential risk for developing PONV include: (1) those with a history of motion sickness and/or PONV; (2) patients undergoing nonorthopedic procedures; and (3) procedures lasting longer than one hour. Such patients may benefit from receipt of a prophylactic antiemetic. Postoperative nausea and vomiting has a debilitating effect that can be differentiated by patients from the effects of surgery itself.
Competing Formate- and Carbon Dioxide-Utilizing Prokaryotes in an Anoxic Methane-Emitting Fen Soil

ABSTRACT Methanogenesis in wetlands is dependent on intermediary substrates derived from the degradation of biopolymers. Formate is one such substrate and is stimulatory to methanogenesis and acetogenesis in anoxic microcosms of soil from the fen Schlöppnerbrunnen. Formate dissimilation also yields CO2 as a potential secondary substrate. The objective of this study was to resolve potential differences between anaerobic formate- and CO2-utilizing prokaryotes of this fen by stable isotope probing. Anoxic soil microcosms were pulsed daily with low concentrations of [13C]formate or 13CO2 (i.e., [13C]bicarbonate). Taxa were evaluated by assessment of 16S rRNA genes, mcrA (encoding the alpha-subunit of methyl-coenzyme M reductase), and fhs (encoding formyltetrahydrofolate synthetase). Methanogens, acetogens, and formate-hydrogen lyase-containing taxa appeared to compete for formate. Genes affiliated with Methanocellaceae, Methanobacteriaceae, Acetobacteraceae, and Rhodospirillaceae were 13C enriched (i.e., labeled) in [13C]formate treatments, whereas genes affiliated with Methanosarcinaceae, Conexibacteraceae, and Solirubrobacteraceae were labeled in 13CO2 treatments. [13C]acetate was enriched in [13C]formate treatments, but labeling of known acetogenic taxa was not detected. However, several phylotypes were affiliated with acetogen-containing taxa (e.g., Sporomusa). Methanosaetaceae-affiliated methanogens appeared to participate in the consumption of acetate. Twelve and 58 family-level archaeal and bacterial 16S rRNA phylotypes, respectively, were detected, approximately half of which had no isolated representatives. Crenarchaeota constituted half of the detected archaeal 16S rRNA phylotypes. The results highlight the unresolved microbial diversity of the fen Schlöppnerbrunnen, suggest that differing taxa competed for the same substrate, and indicate that Methanocellaceae, Methanobacteriaceae, Methanosarcinaceae, and Methanosaetaceae were linked to the production of methane, but they do not clearly resolve the taxa responsible for the apparent conversion of formate to acetate.
Human research review committee requirements in medical journals.

PURPOSE Independent ethical review committees safeguard participants in human research. The purpose of this study was to describe the current ethical guidelines for human research requirements in the Instructions to Authors of the English language medical journals previously studied in 1995. METHODS The instructions to authors of English language medicine journals from the Abridged Index Medicus were searched for any policies regarding guidance on the ethical treatment of human subjects in research. RESULTS More medical journals require independent ethics committee approval of human research now [84/101 (83%)] than 10 years ago [48/102 (47%) (P < 0.001)], and most journals continue to require that this disclosure appear in the manuscript [71/84 (85%) vs. then 37/48 (77%) (P=0.29)]. Fewer medical journal instructions to authors provide no ethical guidelines for human research now [8/101 (8%)] than 10 years ago [25/102 (24%) (P < 0.001)]. No journal required submission of the study approval letter or of the approved protocol. CONCLUSIONS Although medicine journals increasingly require disclosure statements of independent ethics committee approval for human research, they fail to verify such approval beyond taking authors for their word.
Comparison of Point-of-Care Versus Laboratory Troponin Testing in an Emergency Department Setting.

BACKGROUND There have been concerns regarding troponin results accuracy between point-of-care (POC) testing preformed in an emergency department (ED) setting and laboratory testing. The purpose of this study was to compare the results of cardiac troponin I testing as concerns POC testing and laboratory analysis as a way to show that these results are interchangeable. METHODS A retrospective chart review was performed from October 2012 through September 2013 to identify all patients who presented to the ED that received both a POC and laboratory troponin associated with the same blood draw. FINDINGS A total of 189 patients met inclusion criteria. Three laboratory samples were hemolyzed and not available for comparison. Of the remaining 186 samples, when a positive cutoff value of 0.034 ng/mL was used: 37 POC tests were positive and 149 POC tests were negative, sensitivity 0.85 (95% confidence interval [CI] = 0.69-0.94), specificity 0.98 (95% CI = 0.94-0.99), positive predictive value 91.9% (95% CI = 77-97.9%), and negative predictive value 96% (95% CI = 91.1-98.4%). When a POC troponin positive cutoff value of 0.12 ng/mL was used: 20 POC tests were positive and 164 were negative: sensitivity 1.0 (95% CI = 0.8-1.0), specificity 0.99 (95% CI = 0.95-1.0), positive predictive value 91% (95% CI = 69-98.4%), and negative predictive value 100% (95% CI = 97.1-100%). DISCUSSION In an ED setting; POC testing is accurate and correlates well with laboratory testing. Considering that the POC analysis takes a fraction of time to yield results, the validity of its data is important. The results of this study show that the POC system is a suitable test for rapid evaluation of patients presenting to the ED. This correlation increased with a higher testing positive cutoff value (0.12 versus 0.034 ng/mL). These data can assist the emergency physician with rapid identification of evidence of cardiac injury and be assured that the results are accurate. RECOMMENDATIONS POC lab testing should be considered whenever possible to provide the fastest troponin results.