Miracle-dz/UniFAR-FTUs huggingface dataset:
Kinetics of 3′-Deoxy-3′-18F-Fluorothymidine During Treatment Monitoring of Recurrent High-Grade Glioma

3′-deoxy-3′-18F-fluorothymidine (18F-FLT) is used as a biomarker of cell proliferation. We investigated the kinetics of 18F-FLT during treatment of malignant glioma with bevacizumab and irinotecan. Methods: Fifteen patients with recurrent high-grade brain tumors (2 grade III, 13 grade IV) were studied at baseline (study 1 [S1]), after 1 course of therapy (2 wk, study 2 [S2]), and at the end of therapy (6 wk, study 3 [S3]). 18F-FLT (1.5 MBq/kg) was administered intravenously, and dynamic PET was performed for 1 h. Curves representing blood clearance and tumor uptake were derived from factor images and summed frames with thresholding techniques or with a fixed cube. The standard 18F-FLT model was used to estimate the rate constants. 18F-FLT uptake was measured at 2 time points (early standardized uptake value [SUVearly] and late SUV [SUVlate]). Results: Parameters appeared similar for curves derived from factor images and summed frames; the steepest drop occurred between S1 and S2 for transport, influx, SUVearly, and SUVlate. Three groups were distinguished on the basis of clinical outcome: patients who died within 6 mo (group 1 [G1], n = 4), survived 6–12 mo (group 2 [G2], n = 6), and survived more than 1 y (group 3 [G3], n = 5). None of the rate constants was significantly different between the groups. Long-term survivors (G3) showed a significantly different SUV change (in percentage) between S1 and S3, whereas short-term survivors (G1 and G2) did not. Conclusion: Overall, the relative SUV change from S1 to S3 predicted a favorable clinical outcome, whereas the SUV change from S1 to S2 did not. Long-term survivors (G3) showed a significant drop in SUV from S1 to S2 and from S1 to S3. Significant correlations were found between SUV and both the rate constant and the influx rate. The correlation coefficient between SUVlate and influx rate was 0.91, permitting response monitoring by the measurement of 18F-FLT uptake changes.
A Comparison Of Zinc Oxide Eugenol With Endoflas F. S. As Root Canal Sealer In Single Visit Endodontic Therapy

This study was carried out on 21 patients showing periapical rarefaction to evaluate and compare the effectiveness of zinc oxide eugenol and Endoflas F.S. as root canal sealer both clinically and radiographically in single visit endodontic therapy. Endoflas F.S. is a zinc oxide eugenol based cement that has been modified by incorporating calcium hydroxide, iodoform and paramonochlorophenol. Both the sealers showed comparable results clinically and radiographically and rate of success in both the groups was 100% irrespective of culture findings before root canal obturation.
Differential Impact of miR-21 on Pain and Associated Affective and Cognitive Behavior after Spared Nerve Injury in B7-H1 ko Mouse

MicroRNAs (miRNAs) are increasingly recognized as regulators of immune and neuronal gene expression and are potential master switches in neuropathic pain pathophysiology. miR-21 is a promising candidate that may link the immune and the pain system. To investigate the pathophysiological role of miR-21 in neuropathic pain, we assessed mice deficient of B7 homolog 1 (B7-H1), a major inhibitor of inflammatory responses. In previous studies, an upregulation of miR-21 had been shown in mouse lymphocytes. Young (8 weeks), middle-aged (6 months), and old (12 months) B7-H1 ko mice and wildtype littermates (WT) received a spared nerve injury (SNI). We assessed thermal withdrawal latencies and mechanical withdrawal thresholds. Further, we performed tests for anxiety-like and cognitive behavior. Quantitative real time PCR was used to determine miR-21 relative expression in peripheral nerves, and dorsal root ganglia (DRG) at distinct time points after SNI. We found mechanical hyposensitivity with increasing age of naïve B7-H1 ko mice. Young and middle-aged B7-H1 ko mice were more sensitive to mechanical stimuli compared to WT mice (young: p < 0.01, middle-aged: p < 0.05). Both genotypes developed mechanical and heat hypersensitivity (p < 0.05) after SNI, without intergroup differences. No relevant differences were found after SNI in three tests for anxiety like behavior in B7-H1 ko and WT mice. Also, SNI had no effect on cognition. B7-H1 ko and WT mice showed a higher miR-21 expression (p < 0.05) and invasion of macrophages and T cells in the injured nerve 7 days after SNI without intergroup differences. Our study reveals that increased miR-21 expression in peripheral nerves after SNI is associated with reduced mechanical and heat withdrawal thresholds. These results point to a role of miR-21 in the pathophysiology of neuropathic pain, while affective behavior and cognition seem to be spared. Contrary to expectations, B7-H1 ko mice did not show higher miR-21 expression than WT mice, thus, a B7-H1 knockout may be of limited relevance for the study of miR-21 related pain.
Low-functioning hemodialysis patients improve with exercise training.

The Renal Exercise Demonstration Project provided two different approaches to exercise programming to a group of hemodialysis patients. Physical functioning and self-reported health-related quality of life were measured at baseline, after 2 months of independent exercise, and again after 2 months of in-center cycling. This study compares the responses to intervention of patients who initially scored low (<34) on the Physical Component Scale (PCS) on the Medical Outcomes Study Short-Form 36 questionnaire to those who initially scored higher (>34) on the same scale. The high-PCS group scored higher on all physical function tests (normal gait speed, fast gait speed, and sit-to-stand test) at each testing time than the low-PCS group. The high-PCS group improved only on the sit-to-stand test, whereas the low-PCS group improved in all three physical function tests. There were significant differences between the groups in change over time in all the physical scales and the PCS over time, with the low-PCS group showing improvements in response to the intervention and the high-PCS group showing no change over time. No differences in change over time were noted between the groups on the mental scales in either group. We conclude that low-functioning hemodialysis patients can benefit from exercise counseling in both objective measures of physical functioning and self-reported physical functioning. The impact of such interventions seems to be more profound in the lowest functioning patients.
Peptide adsorption on a hydrophobic surface results from an interplay of solvation, surface, and intrapeptide forces

The hydrophobic effect, i.e., the poor solvation of nonpolar parts of molecules, plays a key role in protein folding and more generally for molecular self-assembly and aggregation in aqueous media. The perturbation of the water structure accounts for many aspects of protein hydrophobicity. However, to what extent the dispersion interaction between molecular entities themselves contributes has remained unclear. This is so because in peptide folding interactions and structural changes occur on all length scales and make disentangling various contributions impossible. We address this issue both experimentally and theoretically by looking at the force necessary to peel a mildly hydrophobic single peptide molecule from a flat hydrophobic diamond surface in the presence of water. This setup avoids problems caused by bubble adsorption, cavitation, and slow equilibration that complicate the much-studied geometry with two macroscopic surfaces. Using atomic-force spectroscopy, we determine the mean desorption force of a single spider-silk peptide chain as F = 58 ± 8 pN, which corresponds to a desorption free energy of ≈5 kBT per amino acid. Our all-atomistic molecular dynamics simulation including explicit water correspondingly yields the desorption force F = 54 ± 15 pN. This observation demonstrates that standard nonpolarizable force fields used in classical simulations are capable of resolving the fine details of the hydrophobic attraction of peptides. The analysis of the involved energetics shows that water-structure effects and dispersive interactions give contributions of comparable magnitude that largely cancel out. It follows that the correct modeling of peptide hydrophobicity must take the intimate coupling of solvation and dispersive effects into account.
Ironclad Apps: End-to-End Security via Automated Full-System Verification

An Ironclad App lets a user securely transmit her data to a remote machine with the guarantee that every instruction executed on that machine adheres to a formal abstract specification of the app's behavior. This does more than eliminate implementation vulnerabilities such as buffer overflows, parsing errors, or data leaks; it tells the user exactly how the app will behave at all times. We provide these guarantees via complete, low-level software verification. We then use cryptography and secure hardware to enable secure channels from the verified software to remote users. To achieve such complete verification, we developed a set of new and modified tools, a collection of techniques and engineering disciplines, and a methodology focused on rapid development of verified systems software. We describe our methodology, formal results, and lessons we learned from building a full stack of verified software. That software includes a verified kernel; verified drivers; verified system and crypto libraries including SHA, HMAC, and RSA; and four Ironclad Apps.
Enhanced Antitumor Efficacy of Low-Dose Etoposide with Oncolytic Herpes Simplex Virus in Human Glioblastoma Stem Cell Xenografts

Purpose: Glioblastoma (GBM) inevitably recurs despite surgery, radiation, and chemotherapy. A subpopulation of tumor cells, GBM stem cells (GSC), has been implicated in this recurrence. The chemotherapeutic agent etoposide is generally reserved for treating recurrent tumors; however, its effectiveness is limited due to acute and cumulative toxicities to normal tissues. We investigate a novel combinatorial approach of low-dose etoposide with an oncolytic HSV to enhance antitumor activity and limit drug toxicity. Experimental Design: In vitro, human GBM cell lines and GSCs were treated with etoposide alone, oncolytic herpes simplex virus (oHSV) G47Δ alone, or the combination. Cytotoxic interactions were analyzed using the Chou–Talalay method, and changes in caspase-dependent apoptosis and cell cycle were determined. In vivo, the most etoposide-resistant human GSC, BT74, was implanted intracranially and treated with either treatment alone or the combination. Analysis included effects on survival, therapy-associated adverse events, and histologic detection of apoptosis. Results: GSCs varied in their sensitivity to etoposide by over 50-fold in vitro, whereas their sensitivity to G47Δ was similar. Combining G47Δ with low-dose etoposide was moderately synergistic in GSCs and GBM cell lines. This combination did not enhance virus replication, but significantly increased apoptosis. In vivo, the combination of a single cycle of low-dose etoposide with G47Δ significantly extended survival of mice-bearing etoposide–insensitive intracranial human GSC–derived tumors. Conclusions: The combination of low-dose etoposide with G47Δ increases survival of mice-bearing intracranial human GSC–derived tumors without adverse side effects. These results establish this as a promising combination strategy to treat resistant and recurrent GBM. Clin Cancer Res; 17(23); 7383–93. ©2011 AACR.
The Imbalance Between Metalloproteinases and Their Tissue Inhibitors Is Involved in the Pathogenesis of Dermatitis Herpetiformis

Dermatitis herpetiformis (DH) is a subepidermal autoimmune disease characterized by skin and intestinal lesions consistent with coeliac disease. There are also some data that metalloproteinases (MMPs) are involved in the development of skin lesions in DH, however their exact role in this process is not fully understood. The aim of the study was to investigate whether MMPs and their inhibitors are involved in pathogenesis of DH. Skin biopsies were taken from 13 patients with active DH and from 10 healthy subjects. The localization and expression of MMPs and TIMPs were examined by immunohistochemistry. MMPs expression was detected in basal keratinocytes and in the whole epidermis in all of the DH subjects. Neutrophils in microabscesses and in blister fluid were also positive for MMPs. Expression of TIMPs was moderate or weak in all examined biopsies. Our results allow us to conclude that imbalance between these enzymes takes an important role in the pathogenesis of DH.
Acute traumatic coagulopathy: Whole blood thrombelastography measures the tip of the iceberg

BACKGROUND Thrombelastography (TEG) is suggested as an optimal instrument for the identification of acute traumatic coagulopathy–induced alterations in coagulation status. Patient whole blood (WB) used in TEG analysis is generally collected from a large blood vessel containing representative systemic blood, often close to 40% hematocrit (Hct). Trauma patients often exhibit bleeding from the microvasculature. This study examines early coagulation function changes at the simulated microvascular level based on altered Hct and pH in vitro through TEG analyses of normal donor blood. METHODS Anticoagulated normophysiologic fresh human blood was centrifuged. Individual component effects on coagulation were investigated through variable recombination groups: platelet-rich plasma (PRP), platelet-poor plasma (PPP), and red blood cells (RBCs), which were compared with WB. Acute traumatic coagulopathy–induced acidic microvascular environment was simulated and investigated using tissue factor–activated TEG analysis of variable Hct (40%, 30%, 20%, and 0%) samples and variable [H+]. Incremental replacement of RBC with either PPP or normal saline (NS) simulated resuscitation in vitro was also conducted under similar conditions. RESULTS Only acidified PRP reflected loss of clot strength. Acidified PRP and PPP were delayed equally in clot time. In all groups, inclusion of RBCs normalized clot time. RBC replacement with PPP significantly delayed clot time when samples were acid-challenged, signifying greater acid effect in low Hct microvascular beds. NS simulated resuscitation incurred even greater clotting delays. CONCLUSION Acidemia-induced coagulopathy at the level of the capillary Hct (1) is more severe than at higher Hct levels (larger blood vessels), (2) shows that simulated resuscitation with NS causes greater increases in clot time and decreases in clot strength beyond that which occurs with plasma replacement, and (3) may not accurately be portrayed through common TEG practice of testing systemic WB of greater than 30% Hct.
Numerical investigation of thermal EHL in elliptical contact under impact motion

In this work, the thermal elastohydrodynamic lubrication in elliptical contact under impact motion is investigated numerically by altering oil viscosity and elliptical ratio. The impact-rebound time is shortened with the increase of the elliptical ratio, while a smaller ambient oil viscosity extends the impact-rebound time. Generally speaking, a larger elliptical ratio reduces the maximum load-carrying capacity, increases the value of the minimum film thickness, and lowers the temperature rise. A smaller oil viscosity lowers the pressure and temperature rises and reduces the film thickness.
Peer-to-Peer MIMO Radio Channel Measurements in a Rural Area

The wireless communication channel between vehicular nodes in an ad-hoc network was assessed in a comprehensive measurement and modeling effort. Nodes were equipped with roof mounted azimuthally omnidirectional antennas, and measurements were taken at both short (line-of-sight) and long ranges, at a center frequency of 2.5 GHz. The median MIMO capacity with 8 transmitters and 10 receivers (8 times10) was found to be about five times the corresponding 1times1 SISO capacity, and three times the corresponding 1times10 SIMO capacity. Wideband soundings of such channels were conducted, where the median rms delay spread was found to be 0.6 mus. Measurements, spatial correlation scales, an empirical model of pathloss, and cross- polarization properties of peer-to-peer channels in a rural area are reported.
Increased Levels of Circulating and Tissue mRNAs of Oct-4, Sox-2, Bmi-1 and Nanog is ESCC Patients: Potential Tool for Minimally Invasive Cancer Diagnosis

Background Early stages of esophageal cancer lack a specific symptom, a reliable biomarker and accurate non-invasive diagnostic modalities prompting the pressing need for identification of a marker for early diagnosis of this disease. Methods In the present study we investigated the levels of circulating and tissue mRNAs of Oct-3/4, Sox-2, Nanog and Bmi-1 in esophageal cancer patients using Reverse-Transcription Polymerase Chain Reaction (RT-PCR) with the aim of evaluating their potential as minimally invasive diagnostic markers. Result Increased transcript levels of Oct-4, Sox-2, Bmi-1 and Nanog were detected in (92%), (95%), (75%) and (67%) of the esophageal cancer tissues, respectively as compared with the matched distant normals. Conclusion Interestingly, most of the preneoplastic tissues exhibited increased transcript levels of these stemness markers suggesting their role in early stages of esophageal tumorigenesis. Furthermore, the detection of elevated levels of circulating mRNAs of Oct-4 and Nanog in sera of esophageal cancer patients emphasizes their potential as minimally invasive diagnostic markers for esophageal cancer.
Comparison of Preseason, Midseason, and Postseason Neurocognitive Scores in Uninjured Collegiate Football Players

Background College football players sustain an average of 3 subconcussive blows to the head per game. Concussions correlate with decreases in standardized neurocognitive test scores. It is not known whether repetitive, subconcussive microtrauma associated with participation in a full season of collision sport affects neurocognitive test scores. Hypothesis No difference exists between preseason, midseason, and postseason Standardized Assessment of Concussion (SAC) and Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) scores when collegiate football players sustain subconcussive microtrauma from forceful, repetitive contact activity. Study Design Case series; Level of evidence, 4. Methods Fifty-eight members of a Division III collegiate football team who had no known concussion during the season voluntarily completed the SAC and ImPACT instruments preseason, midseason, and postseason. A repeated measures analysis of variance was used to compare the scores at the 3 time intervals (P < .05). Results No statistically significant decreases were found in overall SAC or ImPACT scores or in any of the domains or composites of the tests (P < .05) when preseason, midseason, and postseason scores were evaluated. Conclusions ImPACT and SAC neurocognitive test scores are not significantly altered by a season of repetitive contact in collegiate football athletes who have not sustained a concussion. Clinical Relevance A diminution in SAC or ImPACT scores in concert with clinical symptoms and findings should be interpreted as evidence of a postconcussive event.
Differential recruitment of limb patterning genes during development and diversification of beetle horns

The origins of novel complex phenotypes represent one of the most fundamental, yet largely unresolved, issues in evolutionary biology. Here we explore the developmental genetic regulation of beetle horns, a class of traits that lacks obvious homology to traits in other insects. Furthermore, beetle horns are remarkably diverse in their expression, including sexual dimorphisms, male dimorphisms, and interspecific differences in location of horn expression. At the same time, beetle horns share aspects of their development with that of more traditional appendages. We used larval RNA interference-mediated gene function analysis of 3 cardinal insect appendage patterning genes,dachshund, homothorax, and Distal-less, to investigate their role in development and diversification of beetle horns within and between species. Transcript depletion of all 3 patterning genes generated phenotypic effects very similar to those documented in previous studies that focused on general insect development. In addition, we found that Distal-less and homothorax, but not dachshund, regulate horn expression in a species-, sex-, body region-, and body size-dependent manner. Our results demonstrate differential co-option of appendage patterning genes during the evolution and radiation of beetle horns. Furthermore, our results illustrate that regulatory genes whose functions are otherwise highly conserved nevertheless retain the capacity to acquire additional functions, and that little phylogenetic distance appears necessary for the evolution of sex- and species-specific differences in these functions.
The BCL2L11 deletion polymorphism is not associated with imatinib resistance in chronic myeloid leukemia patients: meta-analysis

A common deletion polymorphism of the gene Bcl-2 like protein 11 (BCL2L11, BIM) has been reported to cause tyrosine kinase inhibitors (TKIs) resistance in several malignant tumors. However, the conclusions were not consistent in chronic myeloid leukemia (CML) individuals. In order to obtain a reliable conclusion, we systematically searched PubMed, Embase, Web of Science, Chinese Biomedical Database, and China National Knowledge Infrastructure and performed the meta-analysis. Six published articles contain 760 East Asian patients were identified from these electronic databases. The methodological quality of one included trial was high, and the others were moderate. Meta-analysis showed that the rate of TKI resistance between the BIM deletion and wild-type group were no statistical significance (OR = 1.24, 95% CI 0.79–1.95). In conclusion, BIM deletion may not a predictor of TKI resistance in CML individuals in East Asia.
Volumetric response to radiosurgery for brain metastasis varies by cell of origin.

OBJECT The aim of this study was to evaluate the imaging response of brain metastases after radiosurgery and to correlate the response with tumor type and patient survival. METHODS The authors conducted a retrospective review of patients who had undergone Gamma Knife radiosurgery for brain metastases from non-small cell lung cancer (NSCLC), breast cancer, or melanoma. The imaging volumetric response by tumor type was plotted at 3-month intervals and classified as a sustained decrease in tumor volume (Type A), a transient decrease followed by a delayed increase in tumor volume (Type B), or a sustained increase in tumor volume (Type C). These imaging responses were then compared with patient survival and tumor type. RESULTS Two hundred thirty-three patients with metastases from NSCLC (96 patients), breast cancer (98 patients), and melanoma (39 patients) were eligible for inclusion in this study. The patients with NSCLC were most likely to exhibit a Type A response; those with breast cancer, a Type B response; and those with melanoma, a Type C response. Among patients with NSCLC, the median overall survival was 11.2 months for those with a Type A response (76 patients), 8.6 months for those with a Type B response (6 patients), and 10.5 months for those with a Type C response (14 patients). Among patients with breast cancer, the median overall survival was 16.6 months in those with a Type A response (65 patients), 18.1 months in those with a Type B response (20 patients), and 7.5 months in those with a Type C response (13 patients). For patients with melanoma, the median overall survival was 5.2 months in those with a Type A response (26 patients) and 6.7 months in those with a Type C response (13 patients). None of the patients with melanoma had a Type B response. The imaging response was significantly associated with survival only in patients with breast cancer. CONCLUSIONS The various types of imaging responses of metastatic brain tumors after stereotactic radiosurgery depend in part on tumor type. However, the type of response only correlates with survival in patients with breast cancer.