Miracle-dz/UniFAR-FTUs huggingface dataset:
1 COLON 3 Part Case

A 53-year-old male presented with bowel habit change and significant weight loss for 3 months. Physical examination revealed an ill-defined mass at right lower abdomen. His stool examination was normal. Colonoscopy was performed and revealed multiple friable polypoid masses with erosions and white debris on top at the cecum (Figures 1 and 2). Blue laser imaging endoscopy (BLI) showed mucosal inflammation (Figure 3). Ileocecal valve was markedly swelling and causing narrowing of the lumen precluding the passage of a colonoscope into the terminal ileum; however, the remaining colon was normal. Biopsy was done at the mass. Histopathology showed foci of granulomatous inflammation with focal caseous necrosis, and aggregated epitheloid histiocytes (Figure 3). Tissue AFB and PCR-TB were negative.
The role of the intestinal microbiota in the development of atopic disorders

The prevalence of atopic diseases, including eczema, allergic rhinoconjunctivitis and asthma, has increased worldwide, predominantly in westernized countries. Recent epidemiological studies and experimental research suggest that microbial stimulation of the immune system influences the development of tolerance to innocuous allergens. The gastrointestinal microbiota composition may be of particular interest, as it provides an early and major source of immune stimulation and seems to be a prerequisite for the development of oral tolerance. In this review the observational studies of the association between the gut microbiota and atopic diseases are discussed. Although most studies indicated an association between the gut microbiota composition and atopic sensitization or symptoms, no specific harmful or protective microbes can be identified yet. Some important methodological issues that have to be considered are the microbiological methods used (traditional culture vs molecular techniques), the timing of examining the gut microbiota, the definition of atopic outcomes, confounding and reverse causation. In conclusion, the microbiota hypothesis in atopic diseases is promising and deserves further attention. To gain more insight into the role of the gut microbiota in the etiology of atopy, large‐scale prospective birth cohort studies using molecular methods to study the gut microbiota are needed.
Myelodysplasia in autosomal dominant and sporadic monocytopenia immunodeficiency syndrome: diagnostic features and clinical implications

A novel, genetic immunodeficiency syndrome has been recently described, herein termed “MonoMAC”. It is characterized by severe circulating monocytopenia, NK- and B-lymphocytopenia, severe infections with M. avium complex (MAC), and risk of progression to myelodysplasia/acute myelogenous leukemia. Detailed bone marrow analyses performed on 18 patients further define this disorder. The majority of patients had hypocellular marrows with reticulin fibrosis and multilineage dysplasia affecting the myeloid (72%), erythroid (83%) and megakaryocytic (100%) lineages. Cytogenetic abnormalities were present in 10 of 17 (59%). Despite B-lymphocytopenia, plasma cells were present but were abnormal (e.g. CD56+) in nearly half of cases. Increased T-cell large granular lymphocyte populations were present in 28% of patients. Chromosomal breakage studies, cell cycle checkpoint functions, and sequencing of TERT and K-RAS genes revealed no abnormalities. MonoMAC appears to be a unique, inherited syndrome of bone marrow failure. We describe distinctive bone marrow features to help in its recognition and diagnosis. (Clinicaltrials.gov identifiers: NCT00018044, NCT00923364, NCT01212055)
Soft Thrombus Formation in Radiofrequency Catheter Ablation

DEMOLIN, J.M. , et al.: Soft Thrombus Formation in Radiofrequency Catheter Ablation. During RF catheter ablation, local temperature elevation can result in coagulum formation on the ablation electrode, resulting in impedance rise. A recent study has also demonstrated the formation of a so‐called soft thrombus during experimental ablations. This deposit poorly adhered to the catheter tip and did not cause an impedance rise. The mechanism of soft thrombus formation and the role of the natural coagulation system are unknown. The formation of a soft thrombus was investigated experimentally by temperature‐controlled RF delivery in heparinized blood at different heparin concentrations and in serum. After 60 seconds of RF delivery in blood with an electrode target temperature of 80°C, a semisolidified mass had formed around the ablation electrode at all heparin concentrations. A smaller but structurally similar deposit had formed after RF delivery in serum. Scanning electron microscopy analysis revealed that these deposits consist of denaturized and aggregated proteins, and not of a classical thrombus. The formation of the so‐called soft thrombus results from heat induced protein denaturation and aggregation and occurs independent of heparin concentration and also in serum. The formation of such deposits may occur at temperatures well below 100°C, which may have important consequences for further development of ablation technologies.
Antifungal Susceptibility Testing of Fusarium: A Practical Approach

In vitro susceptibility testing of Fusarium is becoming increasingly important because of frequency and diversity of infections and because resistance profiles are species-specific. Reference methods for antifungal susceptibility testing (AFST) are those of Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility (EUCAST), but breakpoints (BPs) have not yet been established. One of the problems is that phylogenetic distances between Fusarium species are much smaller than between species of, e.g., Candida. Epidemiological cutoff values (ECVs) for some Fusarium species have been determined in order to differentiate wild-type from non-wild-type isolates. In clinical routine, commercially available assays such as Etest, Sensititre or others provide essential agreement with reference methods. Our objective is to summarize antifungal susceptibility testing of Fusarium genus in the clinical laboratory: how to do it, when to do it, and how to interpret it.
Food consumption and screen-based sedentary behaviors in European adolescents: the HELENA study.

OBJECTIVE To examine the association between time spent on different sedentary behaviors and consumption of certain food and beverage groups in a sample of European adolescents. DESIGN Data from the Healthy Lifestyle in Europe by Nutrition in Adolescence Cross-sectional Study. SETTING Eight survey centers (Athens, Dortmund, Ghent, Lille, Rome, Stockholm, Vienna, and Zaragoza). PARTICIPANTS A total of 2202 participants (45.5% boys) aged 12½ to 17½ years. MAIN OUTCOME MEASURES Information on sedentary behaviors (weekdays and weekends) collected via a standardized self-reported questionnaire, including watching television, playing computer and video games, using the Internet for studying or recreation, and studying. Food and beverage consumption data of selected groups were obtained using 2 nonconsecutive 24-hour recalls. RESULTS Boys reporting more than 4 h/d of watching television, playing computer games, and using the Internet for recreation were more likely to consume sweetened beverages (weekends) (odds ratio [OR], 1.83 [95% CI, 1.21-2.75]; 1.99 [1.31-3.01]; and 1.73 [1.03-2.91], respectively), and less likely to consume fruit (weekdays) (0.39 [0.21-0.72], 0.37 [0.18-0.77], and 0.39 [0.19-0.78], respectively) than those who spent less than 2 h/d. Girls spending more time per day watching television and playing computer or video games (weekdays) and playing computer games or surfing the Internet for recreation (weekends) were more likely to drink sweetened beverages (OR, 1.89 [95% CI, 1.21-2.94]; 1.57 [1.00-2.46]; 2.14 [1.16-3.97]; and 2.30 [1.24-4.28], respectively) and less likely to consume fruit (weekdays) (0.43 [0.23-0.80], 0.40 [0.19-0.83], 0.37 [0.14-0.94], and 0.42 [0.20-0.85], respectively) than those who spent less than 2 h/d. CONCLUSION Increased television viewing and computer and Internet use during adolescence is associated with higher odds of consumption of sweetened beverages and lower odds of fruit consumption.
Device-guided breathing as treatment for hypertension in type 2 diabetes mellitus: a randomized, double-blind, sham-controlled trial.

IMPORTANCE Biofeedback with device-guided lowering of breathing frequency could be an alternate nonpharmacologic treatment option for hypertension. Evidence from trials with high methodologic quality is lacking. OBJECTIVE To evaluate the effects of device-guided lowering of breathing frequency on blood pressure in patients with type 2 diabetes mellitus and hypertension. DESIGN Single-center, double-blind, sham-controlled trial. SETTING A large nonacademic teaching hospital in the Netherlands. PARTICIPANTS Patients with type 2 diabetes mellitus and hypertension. INTERVENTION Fifteen-minute sessions with either the device that guides breathing through musical tones to a lower breathing frequency (aiming at <10 breaths/min) or a sham device (music without aiming at lowering of breathing frequency) for an 8-week study period. MAIN OUTCOMES AND MEASURES Systolic and diastolic blood pressure measured in the physician's office. RESULTS Forty-eight patients were randomized; 21 patients (88%) in the intervention group and 24 patients (100%) in the control group completed the study. There were no significant changes in systolic and diastolic blood pressure, with a difference in systolic blood pressure of 2.35 mm Hg (95% CI, -6.50 to 11.20) in favor of the control group and a difference in diastolic blood pressure of 2.25 mm Hg (95% CI, -2.16 to 6.67) in favor of the intervention group. Three patients in the intervention group experienced adverse events. CONCLUSIONS AND RELEVANCE This high methodologic quality study shows no significant effect of device-guided lowering of breathing frequency on office-measured blood pressure in patients with type 2 diabetes. On the basis of this study, together with results from all but one previous trial, device-guided lowering of breathing frequency does not appear to be a viable nonpharmacologic option for hypertension treatment.
Evolutionary tipping points in the capacity to adapt to environmental change

Significance Environmental variation is becoming more frequent and unpredictable as a consequence of climate change, yet we currently lack the tools to evaluate the extent to which organisms may adapt to this phenomenon. Here we develop a model that explores these issues and use it to study how changes in the timescale and predictability of environmental variation may ultimately affect population viability. Our model indicates that, although populations can often cope with fairly large changes in these environmental parameters, on occasion they will collapse abruptly and go extinct. We characterize the conditions under which these evolutionary tipping points occur and discuss how vulnerability to such cryptic threats may depend on the genetic architecture and life history of the organisms involved. In an era of rapid climate change, there is a pressing need to understand how organisms will cope with faster and less predictable variation in environmental conditions. Here we develop a unifying model that predicts evolutionary responses to environmentally driven fluctuating selection and use this theoretical framework to explore the potential consequences of altered environmental cycles. We first show that the parameter space determined by different combinations of predictability and timescale of environmental variation is partitioned into distinct regions where a single mode of response (reversible phenotypic plasticity, irreversible phenotypic plasticity, bet-hedging, or adaptive tracking) has a clear selective advantage over all others. We then demonstrate that, although significant environmental changes within these regions can be accommodated by evolution, most changes that involve transitions between regions result in rapid population collapse and often extinction. Thus, the boundaries between response mode regions in our model correspond to evolutionary tipping points, where even minor changes in environmental parameters can have dramatic and disproportionate consequences on population viability. Finally, we discuss how different life histories and genetic architectures may influence the location of tipping points in parameter space and the likelihood of extinction during such transitions. These insights can help identify and address some of the cryptic threats to natural populations that are likely to result from any natural or human-induced change in environmental conditions. They also demonstrate the potential value of evolutionary thinking in the study of global climate change.
Why Are Stock Market Returns Correlated with Future Economic Activities ?

Stock price has been found to provide important information about future economic activities. Fama (1981), Fischer and Merton (1984), and Barro (1990), among many others, document a positive relation between stock market return and subsequent growth in investment and output. These findings are consistent with rational expectations asset pricing models, in which stock price is equal to the sum of discounted future cash flows or dividends. An unexpected increase in the stock price indicates that (i) future dividend growth is higher and/or (ii) future discount rates are lower than previously anticipated. Given that the dividend is an important component of gross domestic product (GDP) and is also likely to be positively correlated with the other components of GDP, the stock price increase may merely reflect higher expected future output. On the other hand, lower discount rates are associated with higher investment and, therefore, higher output.1 Moreover, recognizing a timevarying risk premium, Lettau and Ludvigson (2001b) show that the q theory of investment implies an important relation between the expected stock market return and investment. That is, lower expected stock market return implies lower future stock price and higher future capital cost; accordingly, investment falls over long horizons. The analysis above shows that stock returns are correlated with future economic activities through different channels. In this paper, I address the relative importance of these mechanisms by using Campbell and Shiller’s (1988) method to decompose excess stock market return, eM,t, into three parts: expected return, Et –1eM,t; a shock to the expected future return, ;
mRNA Is an Endogenous Ligand for Toll-like Receptor 3*

Toll-like receptors (TLRs) are the basic signaling receptors of the innate immune system. They are activated by molecules associated with pathogens or injured host cells and tissue. TLR3 has been shown to respond to double stranded (ds) RNA, a replication intermediary for many viruses. Here we present evidence that heterologous RNA released from or associated with necrotic cells or generated by in vitro transcription also stimulates TLR3 and induces immune activation. To assess RNA-mediated TLR3 activation, human embryonic kidney 293 cells stably expressing TLR3 and containing a nuclear factor-κB-dependent luciferase reporter were generated. Exposing these cells to in vitro transcribed RNA resulted in a TLR3-dependent induction of luciferase activity and interleukin-8 secretion. Treatment with in vitro transcribed mRNA activated nuclear factor-κB via TLR3 through a process that was dose-dependent and involved tyrosine phosphorylation. Furthermore, in vitro transcribed natural or 2′-fluoro-substituted mRNA induced the expression of TLR3, interferon regulatory factor-1, tumor necrosis factor-α, and interleukin-1 receptor-associated kinase-M mRNA in human dendritic cells (DCs). DCs responded to mRNA treatment by expressing activation markers, and this maturation was inhibited by antagonistic TLR3-specific antibody. Endogenous RNA released from or associated with necrotic cells also stimulated DCs, leading to interferon-α secretion, which could be abolished by pretreatment of necrotic cells with RNase. These results demonstrate that RNA, likely through secondary structure, is a potent host-derived activator of TLR3. This finding has potential physiologic relevance because RNA escaping from damaged tissue or contained within endocytosed cells could serve as an endogenous ligand for TLR3 that induces or otherwise modulates immune responses.
How muscles define maximum running performance in lizards: an analysis using swing- and stance-phase muscles

SUMMARY Maximum locomotor performance is crucial for capturing prey, escaping predators and many other behaviors. However, we know little about what defines maximum performance in vertebrates. Muscles drive the movement of the limbs during locomotion, and thus likely play a major role in defining locomotor capacity. For lizards, the iliofibularis, a swing-phase muscle, is often linked to ecology and/or performance. However, stance-phase muscles likely limit performance given that they propel the animal. Using a small semi-arboreal lizard (Sceloporus woodi), we compared how swing- and stance-phase muscles relate to maximum running speed and acceleration. We employed both a level and vertical trackway to elicit ecologically relevant locomotor performance. Six individuals were filmed at 250 frames s–1 in lateral view. Following performance trials, upper and lower hindlimbs were sectioned and assessed using histochemistry. Fast glycolytic, fast oxidative and slow oxidative fibers were detected and counted in the gastrocnemius (GA; stance phase) and iliofibularis (IF; swing phase) muscles. In addition, the mean fiber diameter for each fiber type in each muscle was determined, as was the fiber cross-sectional area. We found that properties of the GA, but not the IF, were positively correlated with performance. Interestingly, certain attributes of the GA were correlated with maximum vertical locomotion whereas others were correlated with maximum level locomotion. We conclude that stance phase, not swing phase, limits maximum performance in this species of lizard. In addition, we highlight the need to include properties of stance-phase muscles and a spectrum of ecologically relevant behaviors when attempting to correlate locomotor physiology with ecology and/or performance.
Superinfection as a driver of genomic diversification in antigenically variant pathogens

A new pathogen strain can penetrate an immune host population only if it can escape immunity generated against the original strain. This model is best understood with influenza viruses, in which genetic drift creates antigenically distinct strains that can spread through host populations despite the presence of immunity against previous strains. Whether this selection model for new strains applies to complex pathogens responsible for endemic persistent infections, such as anaplasmosis, relapsing fever, and sleeping sickness, remains untested. These complex pathogens undergo rapid within-host antigenic variation by using sets of chromosomally encoded variants. Consequently, immunity is developed against a large repertoire of variants, dramatically changing the scope of genetic change needed for a new strain to evade existing immunity and establish coexisting infection, termed strain superinfection. Here, we show that the diversity in the alleles encoding antigenic variants between strains of a highly antigenically variant pathogen was equal to the diversity within strains, reflecting equivalent selection for variants to overcome immunity at the host population level as within an individual host. This diversity among strains resulted in expression of nonoverlapping variants that allowed a new strain to evade immunity and establish superinfection. Furthermore, we demonstrated that a single distinct allele allows strain superinfection. These results indicate that there is strong selective pressure to increase the diversity of the variant repertoire beyond what is needed for persistence within an individual host and provide an explanation, competition at the host population level, for the large genomic commitment to variant gene families in persistent pathogens.
The Regulation of Pyruvate Dehydrogenase Activity in Pea Leaf Mitochondria (The Effect of Respiration and Oxidative Phosphorylation)

The regulation of the pea (Pisum sativum) leaf mitochondrial pyruvate dehydrogenase complex by respiratory rate and oxidative phosphorylation has been investigated by measuring the respiratory activity, the redox poise of the quinone pool (Q-pool), and mitochondrial pyruvate dehydrogenase (mtPDC) activity under various metabolic conditions. It was found that, under state 4 conditions, mtPDC activity was unaffected by either the addition of succinate, 2-oxoglutarate, or glycine or the overall respiratory rate and redox poise of the Q-pool but was partially inhibited by NADH due to product inhibition. In the presence of ADP significant inactivation of PDC, which was sensitive to oligomycin, was observed with all substrates, apart from pyruvate, suggesting that inactivation was due to ATP formation. Inactivation of PDC by ADP addition was observed even in the presence of carboxyatractyloside, an inhibitor of the ATP/ADP translocator, suggesting that other mechanisms to facilitate the entry of adenylates, in addition to the adenylate carrier, must exist in plant mitochondria.
Electrophysiologic changes during exercise testing in patients with chronic obstructive pulmonary disease

To determine whether skeletal muscle is involved in the exercise limitation of chronic obstructive pulmonary disease (COPD), we investigated electrical adaptations in muscle during incremental cycling exercise testing. Changes in quadriceps activity were compared using surface electromyography (SEMG) and motor point stimulation in ten COPD patients and ten healthy subjects. Patients showed significantly lower exercise capacity, and M‐wave duration was increased from exercise onset (P < 0.05) with a parallel decrease in amplitude (P < 0.05). The SEMG power spectrum median frequency was always higher (P < 0.04) in patients and its decline was earlier (P < 0.01). The ratio of the root mean square of the SEMG to oxygen uptake was decreased (P < 0.001) during exercise in patients, although it remained constant in controls. Electromyographic parameters were significantly more involved in the exercise limitation than ventilatory factors. Thus, modified electrical activity in muscle appeared in COPD patients from exercise onset, indicating that skeletal muscle function is clearly implicated in the exercise intolerance of these patients. Muscle Nerve 27: 170–179, 2003
On Non-Preemptive VM Scheduling in the Cloud

We study the problem of scheduling VMs (Virtual Machines) in a distributed server platform, motivated by cloud computing applications. The VMs arrive dynamically over time to the system, and require a certain amount of resources (e.g. memory, CPU, etc) for the duration of their service. To avoid costly preemptions, we consider non-preemptive scheduling: Each VM has to be assigned to a server which has enough residual capacity to accommodate it, and once a VM is assigned to a server, its service cannot be disrupted (preempted). Prior approaches to this problem either have high complexity, require synchronization among the servers, or yield queue sizes/delays which are excessively large. We propose a non-preemptive scheduling algorithm that resolves these issues. In general, given an approximation algorithm to Knapsack with approximation ratio r , our scheduling algorithm can provide rβ fraction of the throughput region for β < r. In the special case of a greedy approximation algorithm to Knapsack, we further show that this condition can be relaxed to β<1. The parameters β and r can be tuned to provide a tradeoff between achievable throughput, delay, and computational complexity of the scheduling algorithm. Finally extensive simulation results using both synthetic and real traffic traces are presented to verify the performance of our algorithm.