Miracle-dz/UniFAR-FTUs huggingface dataset:
Oxaliplatin, fluorouracil, and leucovorin for patients with unresectable liver-only metastases from colorectal cancer: a North Central Cancer Treatment Group phase II study.

PURPOSE Surgical resection of liver-only metastases from colorectal cancer has undergone extensive evaluation and review. The use of neoadjuvant chemotherapy to improve the likelihood of resection in disease that is not optimally resectable has not been as well studied. PATIENTS AND METHODS Patients with liver-only metastases from colorectal cancer deemed not optimally resectable by a surgeon with expertise in liver surgery received fluorouracil, leucovorin, and oxaliplatin (FOLFOX4). Patients were periodically reassessed for resectability. Surgical response was classified as completely resectable (S-CR), partially resectable (S-PR), or unresectable (S-UR). Study design specified the accrual of 39 patients, with two or more S-CRs considered evidence of promising activity with respect to increasing the S-CR rate. RESULTS Forty-two of 44 patients were assessable for this analysis. Twenty-five patients (60%) had tumor reduction by serial imaging. Seventeen patients (40%) underwent surgery (S-CR, n = 14; S-PR, n = 1; and S-UR, n = 2) after a median of 6 months of chemotherapy. With a median postsurgical follow-up of 22 months (range, 13 to 32 months), 11 recurrences have occurred in the 15 S-CR and S-PR patients. Median survival time was 26 months. CONCLUSION Our data suggest that FOLFOX4 has a high response rate (complete response, partial response, or reduction) in patients with liver-only metastases from colorectal cancer, allowing for successful resection of disease in a portion of patients initially not judged to be optimally resectable. However, a high recurrence rate after surgery was observed, which, in 73% of patients, involved the liver. Further trials are indicated based on the promising results observed in this trial.
Cache-Based Content Delivery in Opportunistic Mobile Ad Hoc Networks

Over the last few years, multimedia content sharing through different service providers have gained popularity among the Internet users. The development of wireless mobile devices with enhanced features have further fueled this phenomenon. While such content sharing in Internet is accommodated through an overlay architecture, for infrastructure-less environment such as wireless mobile ad hoc networks (MANETs) experiencing intermittent connectivity, the distribution mechanism is not that straightforward. Arising from inherent MANET limitations such as short radio transmission range, sporadic node densities and constrained power, intermittent connectivity limits the ability of the network to provide successful content delivery. Although some solutions have been proposed in literature, they fail to consider the mobility characteristics of nodes for making decisions regarding the caching of contents for future delivery. Moreover, user-centric service requirements are also not addressed where different subscribers prefer different content profiles. To address this issue, a novel content sharing framework with optimized caching strategy is proposed in this paper. Based on the cached subscription profiles, the framework exploits two decision-making technologies namely analytic hierarchy process (AHP) and grey relational analysis (GRA) to evaluate all possible content requests between two meeting nodes and subsequently request the preferred contents for future encounters. Simulation results validate the improved performance of the proposed distribution framework in comparison to the existing schemes.
Genital tract HIV-1 RNA shedding among women with below detectable plasma viral load

Objective:Few studies have assessed longitudinal genital tract HIV-1 shedding. We determined patterns of genital tract HIV-1 RNA shedding over time among women with suppressed plasma viral load (PVL) on antiretroviral treatment. Methods:Paired plasma and genital tract HIV-1 RNA were measured every 4 weeks. Participants were classified as persistent, intermittent, or nonshedders. Longitudinal analysis examined rates of genital tract shedding and the association with PVL, CD4 cell count, and genital tract infections. Markov transition models were used to describe the dynamics of HIV-1 RNA in plasma and genital tract using visit-to-visit transitions from and to detectable and undetectable PVL or genital tract HIV-1 RNA. Results:Fifty-nine women contributed 582 study visits of whom 95 and 98% had below-detectable PVL and genital tract viral load, respectively, at baseline. Thirty-two of 59 women (54%) had detectable HIV-1 RNA at least once in the genital tract. Twenty-two of 59 (37%) women had detectable genital tract HIV-1 RNA during a study visit when PVL was undetectable; 6.8% of the women were persistent shedders, 31% were intermittent shedders, and 45.8% were nonshedders. Sampling three subcompartments increased detection of HIV-1 genital tract viral load compared to sampling a single subcompartment. Overall, genital tract HIV-1 RNA shedding in any subcompartment occurred at about 13% of visits. Shedding in at least one of the three subcompartments occurred at 9% of visits when PVL was undetectable (95% confidence interval 6–14%). Conclusion:Women with below-detectable PVL may have less risk of HIV sexual transmission on a population level, but may continue to be infectious on an individual level.
Seizure generation: The role of nodes and networks

The longstanding dichotomy between the concepts of “focal” and “primary generalized” epilepsy has become increasingly blurred, raising fundamental questions about the nature of ictal onset in localized brain regions versus large‐scale brain networks. We hypothesize that whether an EEG discharge appears focal or generalized is driven by the pattern of connections in brain networks, irrespective of the presence of focal brain abnormality. Using a computational model of a simple “brain” consisting of four regions and the connections between them, we explored the effects of altering connectivity structure versus the effects of introducing an “abnormal” brain region, and the interactions between these factors. Computer simulations demonstrated that electroencephalography (EEG) discharges representing either generalized or focal seizures arose purely as a consequence of subtle changes in network structure, without the requirement for any localized pathologic brain region. Furthermore we found that introducing a pathologic region gave rise to focal, secondary generalized, or primary generalized seizures depending on the network structure. Counterintuitively, we found that decreasing connectivity between regions of the brain increased the frequency of seizure‐like activity. Our findings may enlighten current controversies surrounding the concepts of focal and generalized epilepsy, and help to explain recent observations in genetic animal models and human epilepsies, where loss of white matter pathways was associated with the occurrence of seizures.
The Role of CD8+ T Cells and Their Local Interaction with CD4+ T Cells in Myelin Oligodendrocyte Glycoprotein35–55–Induced Experimental Autoimmune Encephalomyelitis

T cells have an essential role in the induction of multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE). Although for CD4+ T cells it is well established that they contribute to the disease, less is known about the role of CD8+ T cells. Our aim was to determine the individual contribution of CD4+ and CD8+ T cells in myelin oligodendrocyte glycoprotein (MOG)35–55–induced EAE. We investigated MOG35–55–activated CD8+ T cells to clarify their potential to induce or attenuate EAE. We monitored the behavior of CD8+ T cells and their interaction with CD4+ T cells directly at the site of inflammation in the CNS using intravital imaging of the brainstem of EAE-affected living anesthetized mice. We found that mice without CD4+ T cells did not develop relevant clinical signs of disease, although CD8+ T cells were present in the CNS of these mice. These CD8+ T cells displayed reduced motility compared with those in the presence of CD4+ T cells. In mice that harbored CD4+ and CD8+ T cells, we saw a similar extent of clinical signs of EAE as in mice with only CD4+ T cells. Furthermore, the dynamic motility and viability of CD4+ T cells were not disturbed by CD8+ T cells in the lesions of these mice. Therefore, we conclude that in MOG35–55–induced EAE, CD8+ T cell accumulation in the CNS represents instead an epiphenomenon with no impact on clinical disease or on the effects of CD4+ T cells, the latter being the true inducers of the disease.
Different bone remodeling levels of trabecular and cortical bone in response to changes in Wnt/β‐catenin signaling in mice

Trabecular bone and cortical bone have different bone remodeling levels, and the underlying mechanisms are not fully understood. In the present study, the expression of Wnt/β‐catenin signaling and its downstream molecules along with bone mass in trabecular and cortical bone were compared in wild‐type mice, constitutive activation of β‐catenin (CA‐β‐catenin) mice and β‐catenin deletion mice. It was found that the expression level of most of the examined genes such as Wnt3a, β‐catenin, osteocalcin and RANKL/OPG ratio were significantly higher in trabecular bone than in cortical bone in wild‐type mice. CA‐β‐catenin resulted in up‐regulated expression of the above‐mentioned genes except for RANKL/OPG ratio, which were down‐regulated. Also, CA‐β‐catenin led to increased number of osteoblasts, decreased number of osteoclasts and increased bone mass in both the trabecular bone and cortical bone compared with wild‐type mice; however, the extent of changes was much greater in the trabecular bone than in the cortical bone. By contrast, null β‐catenin led to down‐regulated expression of the above‐mentioned genes except for RANKL/OPG ratio. Furthermore, β‐catenin deletion led to decreased number of osteoblasts, increased number of osteoclasts and decreased bone mass when compared with wild‐type mice. Again, the extent of these changes was more significant in trabecular bone than cortical bone. Taken together, we found that the expression level of Wnt/β‐catenin signaling and bone remodeling‐related molecules were different in cortical bone and trabecular bone, and the trabecular bone was more readily affected by changes in the Wnt/β‐catenin signaling pathway. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:812–819, 2017.
Administration of Tetrahydrobiopterin (BH4) Protects the Renal Microcirculation From Ischemia and Reperfusion Injury

BACKGROUND: Abdominal aortic aneurysm surgery with suprarenal cross-clamping is often associated with renal injury. Although the mechanism underlying such injury is unclear, tissue ischemia and reperfusion, which induces endothelial dysfunction and decreases the availability of tetrahydrobiopterin (BH4), may play a role. We evaluated whether BH4 administration prevents renal ischemia/reperfusion injury in an animal model of aortic cross-clamping. METHODS: Nineteen anesthetized, mechanically ventilated, and invasively monitored adult sheep were randomized into 3 groups: sham animals (n = 5) that underwent surgical preparation but no aortic clamping; an ischemia/reperfusion group (n = 7), where the aorta was clamped above the renal arteries for 1 hour, and a BH4 group (n = 7), in which animals received 20 mg/kg of BH4 followed by aortic cross-clamp for 1 hour. Animals were followed for a maximum of 6 hours after reperfusion. The renal microcirculation was evaluated at baseline (before clamping), and 1, 4, and 6 hours after reperfusion using side-stream dark field videomicroscopy. The renal lactate-to-pyruvate ratio was evaluated using microdialysis. The primary outcome was the change in proportion of small perfused vessels before and after injury. Secondary outcomes were renal tissue redox state and renal function. RESULTS: Ischemia/reperfusion injury was associated with increases in heart rate and mean arterial pressure, which were blunted by BH4 administration. From the first to the sixth hour after reperfusion, the small vessel density (estimated mean difference [EMD], 1.03; 95% confidence interval [CI], 0.41–1.64; P = .003), perfused small vessel density (EMD, 0.84; 95% CI, 0.29–1.39; P = .005), and proportion of perfused small vessels (EMD, 8.60; 95% CI, 0.85–16.30; P = .031) were altered less in the BH4 than in the ischemia/reperfusion group. The renal lactate-to-pyruvate ratios were lower in the cortex in the BH4 than in the ischemia/reperfusion group from the first to the sixth hour after reperfusion (EMD, −19.16; 95% CI, −11.06 to 33.16; P = .002) and in the medulla from the first to the fourth hour (EMD, −26.62; 95% CI, −18.32 to 38.30; P = .020; and EMD, −8.68; 95% CI, −5.96 to 12.65; P = .019). At the sixth hour, serum creatinine was lower in the BH4 than in the ischemia/reperfusion group (EMD, −3.36; 95% CI, −0.29 to 1.39; P = .026). CONCLUSIONS: In this sheep model of renal ischemia/reperfusion, BH4 pretreatment reduced renal microvascular injury and improved renal metabolism and function. Further work is needed to clarify the potential role of BH4 in ischemia/reperfusion injury.
ANTIMICROBIAL ACTIVITY OF GYMNOSPERMA GLUTINOSUM (SPRENG.) LESS. (ASTERACEAE) METHANOL EXTRACTS AGAINST HELICOBACTER PYLORI

Background: Prolonged use of antibiotics may lead to the selection of drug-resistant bacteria; as a result, efforts are being made to identify new and effective antimicrobial agents, particularly, from medicinal plants, against bacterial infections. Antimicrobial activity of Gymnosperma glutinosum against Helicobacter pylori has not yet been reported. Materials and methods: The antibacterial in vitro effect of Gymnosperma glutinosum methanol leaf extracts against Helicobacter pylori (ATCC 43504) was evaluated in liquid medium by the colorimetric 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) reduction assay and in solid medium by the colony forming units (CFU) method. Results: Methanol extracts significantly (p<0.05) inhibited in vitro H. pylori growth in liquid medium from 24% to 82% at concentrations ranging from 31.25 mg/ml to 500 mg/ml, respectively, and in solid medium the extracts caused significant (p<0.05) 52% and 100% bacterial growth inhibition at concentrations of 250 μg/mL and 500 μg/mL, respectively, as compared with untreated control. Methanol vehicle did not affect H. pylori growth. Conclusion: The observed antibacterial effect of G. glutinosum extracts may be of benefit as an adjuvant treatment of diseases caused by H. pylori.
Healthy and Happy: Animal Welfare as an Integral Part of Sustainable Agriculture

Abstract Good animal welfare is necessary if an agricultural system is to be sustainable. Although we have been concerned about the welfare of our animals since we first domesticated them and became dependent on their health and reproduction, this article focuses mainly on the development of the animal welfare debate since the 1960s. It presents animal welfare as a science that arose from society's concern about the way animals are kept. These moral and ethical concerns lead to it having a value framework that must also be taken into consideration. Different definitions of animal welfare, as well as examples of research, are presented and discussed in the light of developments in this area. For example, in recent years there has been an increased interest among consumers for animal-friendly products, as there has been for environment friendly products, and this has stimulated the move from experimental studies of animal welfare to its application in practice and to monitoring animal welfare on farms. Traditionally such measurements have been resource based, e.g. specifying the minimum amount of feeding space or the maximum stocking density, but now the trend is toward animal-based measures, such as the number of lame animals, body condition, etc.
Patterns of Chronic Injury in Pediatric Renal Allografts

Background. In pediatric recipients, the pathophysiology of chronic renal allograft injury is poorly understood. Methods. We studied the evolution and determinants of tubulointerstitial, vascular, and glomerular injury in 240 pediatric protocol renal allograft biopsies during the first 5 years posttransplant. Results. Chronic tubulointerstitial injury (ci, ct) developed predominantly during the first 12 months posttransplant, whereas chronic vascular damage (cv, and arteriolar hyalinosis [ah]) and global glomerulosclerosis (gs) became increasingly prevalent at 25 to 36 months and beyond. Chronic interstitial lesions were associated with acute rejection and borderline histology (odds ratio [OR] 2.3, P<0.04), recipient body surface area less than 1.0 m2 (OR 3.6, P<0.05), and obesity (OR 2.0, P<0.03). Determinants of ct were acute rejection (OR 2.6, P=0.02) and acute tubular necrosis (OR 2.8, P<0.04). Vascular fibrous intimal thickening and ah were associated with donor hypertension (OR 3.6, P=0.001) and recipient body surface area less than 1.0 m2 (OR 2.6, P=0.02), respectively. The severity of ah correlated with the incidence of gs (r=0.32, P<0.0001), with 7.8% gs for ah0, 14.3% gs for ah1, 60.0% gs for ah2, and 95.5% gs for ah3 (median values). Antibody induction conferred protection from ci (OR 0.31, P=0.008), ct (OR 0.33, P=0.002), and ah (OR 0.12, P<0.001) progression. Conclusions. By 5 years posttransplant, pediatric renal allografts manifest a substantial burden of tubulointerstitial and microvascular injury. These lesions are associated with donor hypertension, acute inflammation, renal hypoperfusion, obesity, and calcineurin inhibitor toxicity. The pervasiveness and rapid progression of microvascular lesions at 25 to 36 months suggest that attempts at reducing calcineurin inhibitor exposure should be made before two years posttransplant.
Similarities and differences in lipid metabolism of chloroplasts isolated from 18:3 and 16:3 plants.

Photosynthetically active chloroplasts retaining high rates of fatty acid synthesis from [1-(14)C]acetate were purified from leaves of both 16:3 (Solanum nodiflorum, Chenopodium album) and 18:3 plants (Amaranthus lividus, Pisum sativum). A comparison of lipids into which newly synthesized fatty acids were incorporated revealed that, in 18:3 chloroplasts, enzymic activities catalyzing the conversion of phosphatidate to diacylglycerol and of diacylglycerol to monogalactosyl diacylglycerol (MGD) were significantly less active than in 16:3 chloroplasts. In contrast, labeling rates of MGD from UDP-[(14)C]gal were similar for both types of chloroplasts.The composition and positional distribution of labeled fatty acids within the glycerides synthesized by isolated 16:3 and 18:3 chloroplasts were similar and in each case only a C18/C16 diacylglycerol backbone was synthesized. In nodiflorum chloroplasts, C18:1/C16:0 MGD assembled de novo was completely desaturated to the C18:3/C16:3 stage.Whereas newly synthesized C18/C18 MGD could not be detected in any of these chloroplasts if incubated with [(14)C]acetate after isolation, chloroplasts isolated from acetate-labeled leaves contained MGD with labeled C18 fatty acids at both sn-1 and sn-2 positions. Taken together, these results provide further evidence on an organellar level for the operation of pro- and eucaryotic pathways in the biosynthesis of MGD in different groups of plants.
When program analysis meets mobile security: an industrial study of misusing Android internet sockets

Despite recent progress in program analysis techniques to identify vulnerabilities in Android apps, significant challenges still remain for applying these techniques to large-scale industrial environments. Modern software-security providers, such as Qihoo 360 and Pwnzen (two leading companies in China), are often required to process more than 10 million mobile apps at each run. In this work, we focus on effectively and efficiently identifying vulnerable usage of Internet sockets in an industrial setting. To achieve this goal, we propose a practical hybrid approach that enables lightweight yet precise detection in the industrial setting. In particular, we integrate the process of categorizing potential vulnerable apps with analysis techniques, to reduce the inevitable human inspection effort. We categorize potential vulnerable apps based on characteristics of vulnerability signatures, to reduce the burden on static analysis. We flexibly integrate static and dynamic analyses for apps in each identified family, to refine the family signatures and hence target on precise detection. We implement our approach in a practical system and deploy the system on the Pwnzen platform. By using the system, we identify and report potential vulnerabilities of 24 vulnerable apps (falling into 3 vulnerability families) to their developers, and some of these reported vulnerabilities are previously unknown. The apps of each vulnerability family in total have over 50 million downloads. We also propose countermeasures and highlight promising directions for technology transfer.
Effects of Response Eccentricity and Relative Position on Orthogonal Stimulus—Response Compatibility with Joystick and Keypress Responses

When unimanual left—right movement responses are made to up—down stimuli, performance is better with the up—right/down—left mapping when responding in the right hemispace and with the up—left/down—right mapping when responding in the left hemispace. We evaluated whether this response eccentricity effect is explained best in terms of rotational properties of the hand (the end-state comfort hypothesis) or asymmetric coding of the stimulus and response alternatives (the salient features coding hypothesis). Experiment 1 showed that bimanual keypresses yield a response eccentricity effect similar to that obtained with unimanual movement responses. In Experiment 2, an inactive response apparatus was placed to the left or right of the active response apparatus to provide a referent. For half of the participants, the active and inactive apparatuses were joysticks, and for half they were response boxes with keys. For both response types, an up—right/down—left advantage was evident when the relative position of the active response apparatus was right but not when it was left. That bimanual keypresses yield similar eccentricity and relative location effects to those for unimanual movements is predicted by the salient features coding perspective but not by the end-state comfort hypothesis.