Miracle-dz/UniFAR-FTUs huggingface dataset:
Inhibition of Circulating Dipeptidyl Peptidase 4 Activity in Patients with Metastatic Prostate Cancer*

Cancer is responsible for many deaths and is a major source of healthcare expenditures. The identification of new, non-invasive biomarkers might allow improvement of the direct diagnostic or prognostic ability of already available tools. Here, we took the innovative approach of interrogating the activity of exopeptidases in the serum of cancer patients with the aim of establishing a distinction based on enzymatic function, instead of simple protein levels, as a means to biomarker discovery. We first analyzed two well-characterized mouse models of prostate cancer, each with a distinct genetic lesion, and established that broad exopeptidase and targeted aminopeptidase activity tests reveal proteolytic changes associated with tumor development. We also describe new peptide-based freeze-frame reagents uniquely suited to probe the altered balance of selected aminopeptidases, as opposed to the full array of exopeptidases, and/or their modulators in patient serum or plasma. One particular proteolytic activity was impaired in animals with aggressive disease relative to cancer-free littermates. We identified the protease in question as dipeptidyl peptidase 4 (DPP4) by analyzing selected knockout mice and evaluating the effect of specific inhibitors. DPP4 activity was also reduced in the sera of patients with metastatic prostate cancer relative to patients with localized disease or healthy controls. However, no significant differences in DPP4 serum levels were observed, which established the loss of activity as the result of impaired enzymatic function. Biochemical analysis indicated that reduced activity was the result not of post-translational modifications or allosteric changes, but instead of a low-molecular-weight inhibitor. After we adjusted for age and total prostate-specific antigen, reduced DPP4 activity remained a significant predictor of cancer status. The results of this proof-of-principle study suggest that DPP4 activity might be a potential blood-based indicator of the presence of metastatic cancer of prostatic origin, either by itself or, more likely, as a means to improve the sensitivity and specificity of existing markers.
The Impact of Ombudsmen

Introducing, maintaining and/or reforming the institution of an ombudsman often provokes universal questions of added value: (Why) should we have such an office in the first place? (How) does it meet the requirements for which it was initially established? Can we identify an apparent surplus from its insertion in a given polity? In order to answer these questions, it is crucial to try to grasp the effects and the impact of the institution in the context it is operating in. It is with this central but challenging aspect of the office of ombudsman that this volume deals. By tackling those questions and many more, this volume provides a unique perspective on assessing the impact of ombudsmen. It does so by combining insights from practitioners as well as academics and by covering a wide range of countries, levels and systems from all over the world. Moreover, both reputations as well as realities, trajectories and networks are dealt with throughout the volume.
Overlooked potential of systems with Markovian coefficients

The usual system of linear stochastic difference equations with Markovian coefficients has been generalized to cover Rn valued processes which jump simultaneously with and due to jumps of the coefficients. The additional modelling potential is illustrated for a manoeuvring aircraft. Once being familiar with this overlooked potential of systems with Markovian coefficients, their use is remarkably simple. To filter partial observations of the generalized system candidate algorithms are reviewed, in particular the Generalized Pseudo Bayes algorithms and the more recent Interacting Multiple Model (IMM) algorithm. The IMM algorithm for the generalized system is applied to tracking a manoeuvring aircraft. The results indicate that the generalized models and the associated IMM algorithm has the potential to yield trackers that perform better than the existing decision-directed trackers.
Adult Pituitary Stem Cells: From Pituitary Plasticity to Adenoma Development

The pituitary needs high plasticity of the hormone-producing cell compartment to generate the continuously changing hormonal signals that govern the key physiological processes it is involved in, as well as homeostatic cell turnover. However, the underlying mechanisms are still poorly understood. It was proposed that adult stem cells direct the generation of newborn cells with a hormonal phenotype according to the physiological requirements. However, only in recent years adult pituitary stem cells have begun to be phenotypically characterized in several studies that identified multiple stem/progenitor cell candidates. Also considering the incompletely defined features of this cell subpopulation, some discrepancies among the different reports are clearly apparent and long-term self-renewal remains to be unequivocally demonstrated. Here, all the recently published evidence is analyzed, trying, when possible, to reconcile the results of the different studies. Finally, with the perspective of shedding light on pituitary tumorigenesis and the development of potentially new pharmacological approaches directed against these cells, very recent evidence on the presence of putative cancer stem cells in human pituitary adenomas is discussed.
Different Roles of Pitch and Duration in Distinguishing Word Stress in English

Our study investigated the pitch and duration properties of word stress in a large speech corpus. We concluded that pitch and duration play different roles in distinguishing word-level stress classes. In the case of pitch, primary-stress vowels were different from secondary-stress and reduced vowels; in the case of duration, reduced vowels were different from the other two types of vowels.
Evaluation of bone heating, drill deformation, and drill roughness after implant osteotomy: guided surgery and classic drilling procedure.

PURPOSE This study evaluated and compared bone heating, drill deformation, and drill roughness after several implant osteotomies in the guided surgery technique and the classic drilling procedure. MATERIALS AND METHODS The tibias of 20 rabbits were used. The animals were divided into a guided surgery group (GG) and a control group (CG); subgroups were then designated (G0, G1, G2, G3, and G4, corresponding to drills used 0, 10, 20, 30 and 40 times, respectively). Each animal received 10 sequential osteotomies (5 in each tibia) with each technique. Thermal changes were quantified, drill roughness was measured, and the drills were subjected to scanning electron microscopy. RESULTS Bone temperature generated by drilling was significantly higher in the GG than in the CG. Drill deformation in the GG and CG increased with drill use, and in the CG a significant difference between G0 and groups G3 and G4 was observed. In the GG, a significant difference between G0 and all other groups was found. For GG versus CG, a significant difference was found in the 40th osteotomy. Drill roughness in both groups was progressive in accordance with increased use, but there was no statistically significant difference between subgroups or between GG and CG overall. CONCLUSION During preparation of implant osteotomies, the guided surgery technique generated a higher bone temperature and deformed drills more than the classic drilling procedure. The increase in tissue temperature was directly proportional to the number of times drills were used, but neither technique generated critical necrosis-inducing temperatures. Drill deformation was directly proportional to the number of times the drills were used. The roughness of the drills was directly proportional to the number of reuses in both groups but tended to be higher in the GG group.
Role of endoscopic ultrasonography in screening and treatment of pancreatic endocrine tumours in asymptomatic patients with multiple endocrine neoplasia type 1

Patients with multiple endocrine neoplasia (MEN) type 1 risk premature death from pancreatic endocrine tumours (PETs). Endoscopic ultrasonography (EUS) is the most sensitive imaging modality for small PETs. A screening and therapeutic approach for asymptomatic patients is delineated in which EUS plays a pivotal role.
Cost-Efficient Mapping for Fault-Tolerant Virtual Networks

Network virtualization provides more flexibility in network provisioning as it offers physical infrastructure providers (PIP) the possibility of smoothly rolling out many separate networks on top of an existing infrastructure. A major challenge is the embedding problem of mapping virtual networks (VNs) onto PIP infrastructure. In the literature, a good deal of research has focused on providing heuristic approaches to this NP-hard problem, usually with the assumption that the PIP infrastructure is operational at all times. In virtualization environment, a single physical node/link failure can result in one or more logical link failures as it effects all VNs with a mapping that spans over. Setting up a dedicated backup for each VN embedding that is not shared with others is an inefficient use of resources. To address these concerns, this paper proposes two classes of periodic VN protection against link and node failures: (a) in the physical layer, by using a path or segment p-cycle technique and a column generation optimization model, and (b) in the VN layer, by augmenting the topology with redundant resources and subsequently applying a column generation mapping model. Our simulations show a clear advantage of our approaches over benchmarks in terms of PIP profit, backup cost/rate and resource use.
Contributions to the study of the pathogenic mechanisms ofHCV and their implications for a better understanding of the disease

Electronic transmission and confocal microscopy were used to study hepatic biopsies and peripheral blood mononuclear cells (PBMC) from 150 Cuban chronic hepatitis C patients. The study yielded novel data about the detection of the capsid of HCV in extra-parenchymal liver cells. Apoptotic cells were detected in liver tissue and PBMC using the TUNEL technique and the activation of apoptotic effectors. For the first time it was possible to observe the presence of positiveand negative-polarity RNA in hepatocytes and PBMC for 80% of the samples taken from serum RNA-negative patients with histological and biochemical remission. Another new contribution was the demonstration that extra-parenchymal liver cells and PBMC constitute reservoirs for HCV replication. The presence of HCcAg and core particles of HCV, observed for the first time in stellate cells, proved that HCV can directly infect this cell type. Since stellate cells can trans-differentiate into myofibroblast-like cells and thus modulate the process of hepatic fibrogenesis, this finding underscores the relevance of these cells, together with fibroblasts, for the development of hepatic cirrhosis. The application of these findings has important repercussions for the diagnosis, followup and prognosis of hepatitis C.
Tao and the Lost Art of Leadership

I often tell people that I am literally a lifetime student of academic leadership. I grew up watching myfather navigate his career in the academy as a professor of Sociology, including serving asDepartment Chair. Much to his pleasure I followed suit, pursuing a fun and challenging career as aprofessor of Communication in the same state university system. Over the course of my journey inacademe, I’ve observed, and participated in, almost every level of academic leadership. From servingas chair of too many committees to remember, Department Chair, Vice-President of the AcademicSenate, University Ombudsperson, and now Associate Dean, I’ve encountered both the good and badin leadership at the university level.
Look Wider to Match Image Patches With Convolutional Neural Networks

When a human matches two images, the viewer has a natural tendency to view the wide area around the target pixel to obtain clues of right correspondence. However, designing a matching cost function that works on a large window in the same way is difficult. The cost function is typically not intelligent enough to discard the information irrelevant to the target pixel, resulting in undesirable artifacts. In this letter, we propose a novel convolutional neural network (CNN) module to learn a stereo matching cost with a large-sized window. Unlike conventional pooling layers with strides, the proposed per-pixel pyramid-pooling layer can cover a large area without a loss of resolution and detail. Therefore, the learned matching cost function can successfully utilize the information from a large area without introducing the fattening effect. The proposed method is robust despite the presence of weak textures, depth discontinuity, illumination, and exposure difference. The proposed method achieves near-peak performance on the Middlebury benchmark.
UDCA exerts beneficial effect on mitochondrial dysfunction in LRRK2G2019S carriers and in vivo

Objective: To further characterize mitochondrial dysfunction in LRRK2G2019S mutant Parkinson disease (PD) patient tissue (M-LRRK2G2019S), determine whether ursodeoxycholic acid (UDCA) also exerts a beneficial effect on mitochondrial dysfunction in nonmanifesting LRRK2G2019S mutation carriers (NM-LRRK2G2019S), and assess UDCA for its beneficial effect on neuronal dysfunction in vivo. Methods: Intracellular adenosine 5′-triphosphate (ATP) levels, oxygen consumption, and activity of the individual complexes of the mitochondrial respiratory chain as well as mitochondrial morphology were measured in M-LRRK2G2019S, NM-LRRK2G2019S, and controls. UDCA was assessed for its rescue effect on intracellular ATP levels in NM-LRRK2G2019S and in a LRRK2 transgenic fly model with dopaminergic expression of LRRK2G2019S. Results: Crucial parameters of mitochondrial function were similarly reduced in both M-LRRK2G2019S and NM-LRRK2G2019S with a specific decrease in respiratory chain complex IV activity. Mitochondrial dysfunction precedes changes in mitochondrial morphology but is normalized after siRNA-mediated knockdown of LRRK2. UDCA improved mitochondrial function in NM-LRRK2G2019 and rescued the loss of visual function in LRRK2G2019S flies. Conclusion: There is clear preclinical impairment of mitochondrial function in NM-LRRK2G2019S that is distinct from the mitochondrial impairment observed in parkin-related PD. The beneficial effect of UDCA on mitochondrial function in both NM-LRRK2G2019S and M-LRRK2G2019S as well as on the function of dopaminergic neurons expressing LRRK2G2019S suggests that UDCA is a promising drug for future neuroprotective trials.
Association Between Symptoms of Depression and Anxiety With Heart Rate Variability in Patients With Implantable Cardioverter Defibrillators

Objective: This study investigated whether depression and anxiety symptoms are associated with measures of autonomic nervous system dysfunction in patients with implantable cardioverter defibrillators who are at high risk of cardiac rhythm disturbances. Depression and anxiety are associated with autonomic nervous system dysfunction, which may promote the risk of malignant cardiac arrhythmias. Methods: Patients with an implantable cardioverter defibrillator (ICD) underwent ambulatory electrocardiographic (ECG) monitoring (n = 44, mean age = 62.1 ± 9.3 years). Depression was assessed using the Beck Depression Inventory and anxiety was evaluated using the Taylor Manifest Anxiety Scale. Heart rate variability was assessed using time (RMSSD, pNN50, and SDNN) and frequency domain measures derived from 24-hour R-R intervals. Multivariate models were adjusted for age, sex, hypertension, diabetes, and smoking status. Results: Defibrillator patients with elevated depression symptoms (n = 12) had significantly lower RMSSD (15.25 ± 1.66 ms versus 24.97 ± 2.44 ms, p = .002) and pNN50 (1.83 ± 0.77 versus 5.61 ± 1.04, p = .006) than defibrillator patients with low depression symptoms (n = 32). These associations remained significant after multivariate adjustment for covariates. ICD patients with high anxiety levels (n = 10) displayed lower RMSSD (p = .013), which became marginally significant when adjusting for covariates (p = .069). Conclusions: Depression and anxiety in defibrillator patients are associated with autonomic nervous system dysfunction indices of reduced parasympathetic control. Autonomic nervous system dysfunction may partially explain the association between depression and anxiety with life-threatening cardiac outcomes in vulnerable patients. ICD = implantable cardioverter defibrillators; HRV = heart rate variability; BDI = Beck Depression Inventory; BMI = body mass index.
A study of the effects of co-branding between low-carbon islands and recreational activities

The development of sustainable tourism on islands is increasingly based on the concept of “low carbon” practices. From a co-branding perspective, this study discusses how to combine recreational activities to create a differentiated tourism landscape, and thus positively influence post-visit tourist reactions when the focal islands emphasize their low-carbon practices. This study used a questionnaire survey to study Taiwan's Penghu and Republic of Palau, two islands that have adopted low-carbon policies, and a total of 341 and 298 valid samples were collected, respectively. The findings are the following. (1) Regardless of the island, tourists recognized the low-carbon strategies of both islands, with those of Palau receiving greater attention. (2) The tourists were most familiar with motorized water activities, and the degree of participation in such activities was the highest. However, there were significant differences in degrees of familiarity with and participation in other recreational activities. (3) On both Penghu and Palau, islands and motorized water activities represent the optimal match, and the optimal match percentage of Penghu for all types of recreational activity is 67%. (4) Compared with tourists on Palau, those on Penghu are more willing to recommend a visit to others or revisit the island.
Global Food Prices and Domestic Inflation: Some Cross-Country Evidence

We study the impact of global food price shocks on domestic inflation in a large group of countries. For advanced economies, a 10% increase in global food inflation raises domestic inflation by about 0.5 percentage point after a year; however, the impact has declined over time and become less persistent. The global food price shocks of the 2000s had a much bigger impact on domestic inflation in emerging and developing economies than in advanced economies. This could reflect the smaller share of food in the consumption baskets in advanced economies. We also provide evidence that inflation expectations are more anchored in advanced than in emerging economies, which could also explain the smaller impact on inflation from global food price shocks.
Incentive mechanism design for delayed WiFi offloading

WiFi offloading helps serve ever-increasing data traffic in cellular networks and mitigate the network congestion. Yet it can only apply to cellular users within WiFi coverage. Recently, delayed WiFi offloading is proposed to exploit users' mobility to purposely travel to WiFi coverage for data offloading. Its successful implementation depends on users' willingness to delay ongoing cellular data services until entering WiFi coverage. This paper proposes an incentive mechanism to allow a network operator to optimally reward his users to participate in delayed WiFi offloading, so as to reduce the network congestion. We formulate the design problem as a two-stage Stackelberg game: in Stage I, the operator announces a uniform reward to users to delay their existing cellular services; and in Stage II, each user decides to join the delayed offloading or not, depending on the reward, the network congestion, and his estimation of waiting cost for WiFi connection. The operator and users may or may not know all users' mobility and waiting cost information; thus, we propose optimal reward mechanisms under various information availability scenarios. Interestingly, we show that the optimal reward does not always increase with the cellular traffic load, as the increased network congestion can also help motivate users to switch to WiFi networks.
Weaknesses in the classification criteria for antithrombotic-related major bleeding events

Summary We asked two physicians to review the medical records (electronic and paper) of 100 patients on antithrombotics. The physicians used published classification criteria to identify all of the bleeding events that the patients experienced. The goal of the review was to investigate whether the physicians would identify the same antithrombotic related major bleeding events (ARMBEs) for each patient. The correct identification and classification of multiple bleeding events is a prerequisite for studies of antithrombotic treatment practices during hospitalization that predispose patients to ARMBEs. In addition, we were interested in the reasons for disagreement between the physicians, so that we could find ways of improving their agreement. The reviewers identified 299 bleeding events for the 100 patients. They disagreed on whether 29 of the events represented an ARMBE occurring during hospitalization. With a kappa statistic of 0.49 (95% confidence interval, 0.31 to 0.66) the agreement was moderate. The reviewers most often disagreed either because they misinterpreted the data (12 events) or because the classification criteria for ARMBEs were not explicit enough (9 events). Disagreement took two main forms: either the reviewers disagreed on ARMBEs by not identifying the same bleeds (11 events) or by not applying the severity criteria appropriately (7 events). Because the main type of disagreement was not identifying the same bleeds, a study investigating the antithrombotic treatment practices that predispose patients to ARMBEs would be threatened. We therefore proposed supplementing the existing classification criteria with additional rules to avoid ambiguities in patients with multiple events.
Psychiatric Disorder and Metabolic Control Among Youths With IDDM: A longitudinal study

OBJECTIVE To investigate the longitudinal relationship between psychiatric diagnostic variables and metabolic control among youths with IDDM. RESEARCH DESIGN AND METHODS A group of 88 youths, 8 to 13 years old at onset of 1DDM, were evaluated repeatedly during a 9-year follow-up period, on average, using a standardized psychiatric protocol. Levels of HbA1 were also assessed repeatedly. Psychiatric diagnoses were derived independently of HbA1 values. RESULTS In univariate longitudinal analyses, the psychiatric diagnosis of noncompliance with medical treatment was significantly related to HbA1 level. There was a trend of an association between any major psychiatric disorder, as well as nondepressive disorder, and HbA1 Interaction terms between IDDM duration (or age) and psychiatric variables were also significantly related to metabolic control. According to the final multivariate model of repeatedly assessed HbA1, noncompliance with medical treatment (irrespective of IDDM duration) and the interaction between nondepressive psychiatric disorder and IDDM duration contributed to worse metabolic control. CONCLUSIONS We found some support for the hypothesis that psychiatric morbidity negatively affects blood glucose regulation and that its consequences are more marked the longer young patients have had IDDM. We did not confirm the hypothesis that depressive illness has particularly deleterious consequences on metabolic control. Noncompliance with medical treatment and having had nondepressive psychiatric illness in interaction with IDDM duration account for a statistically significant but clinically modest amount of variability in HbA1 over time. The weak relationship among these variables may explain the inconsistent findings in the literature regarding psychiatric morbidity and metabolic control.