Miracle-dz/UniFAR-FTUs huggingface dataset:
PG-mediated closure of paracellular pathway and not restitution is the primary determinant of barrier recovery in acutely injured porcine ileum.

Small bowel epithelium is at the frontline of intestinal barrier function. Restitution is considered to be the major determinant of epithelial repair, because function recovers in parallel with restitution after acute injury. As such, studies of intact mucosa have largely been replaced by migration assays of cultured epithelia. These latter studies fail to account for the simultaneous roles played by villous contraction and paracellular permeability in recovery of barrier function. NSAIDs result in increased intestinal permeability and disease exacerbation in patients with inflammatory bowel disease (IBD). Thus we examined the reparative attributes of endogenous PGs after injury of ileal mucosa by deoxycholate (6 mM) in Ussing chambers. Recovery of transepithelial electrical resistance (TER) from 20-40 Omega.cm2 was abolished by indomethacin (Indo), whereas restitution of 40-100% of the villous surface was unaffected despite concurrent arrest of villous contraction. In the presence of PG, resident crypt and migrating epithelial cells were tightly apposed. In tissues treated with Indo, crypt epithelial cells had dilated intercellular spaces that were accentuated in the migrating epithelium. TER was fully rescued from the effects of Indo by osmotic-driven collapse of the paracellular space, and PG-mediated recovery was significantly impaired by blockade of Cl- secretion. These studies are the first to clearly distinguish the relative contribution of paracellular resistance vs. restitution to acute recovery of epithelial barrier function. Restitution was ineffective in the absence of PG-mediated paracellular space closure. Failure of PG-mediated repair mechanisms may underlie barrier failure resulting from NSAID use in patients with underlying enteropathy.
Discrete-time anti-windup: Part 2 — Extension to the sampled-data case

The formulation of a discrete-time anti-windup scheme for linear systems with constrained control signals is extended to the sampled-data case. Thus, the control of a continuous-time linear plant via a discrete linear nominal controller and a discrete anti-windup compensator is considered. Stability of the anti-windup compensator is equivalent to the known discrete problem while a hybrid induced l2/L2 norm is considered for anti-windup performance. Linear sampled-data lifting techniques are used to reduce the hybrid problem to an optimization problem in the discrete-time domain. A flight control example shows the effectiveness of the discrete and the sampled-data technique.
Role of the miR-17∼92 cluster family in cerebellar and medulloblastoma development

ABSTRACT The miR-17∼92 cluster family is composed of three members encoding microRNAs that share seed sequences. To assess their role in cerebellar and medulloblastoma (MB) development, we deleted the miR-17∼92 cluster family in Nestin-positive neural progenitors and in mice heterozygous for the Sonic Hedgehog (SHH) receptor Patched 1 (Ptch1+/−). We show that mice in which we conditionally deleted the miR-17∼92 cluster (miR-17∼92floxed/floxed; Nestin-Cre+) alone or together with the complete loss of the miR-106b∼25 cluster (miR-106b∼25−/−) were born alive but with small brains and reduced cerebellar foliation. Remarkably, deletion of the miR-17∼92 cluster abolished the development of SHH-MB in Ptch1+/− mice. Using an orthotopic transplant approach, we showed that granule neuron precursors (GNPs) purified from the cerebella of postnatal day 7 (P7) Ptch1+/−; miR-106b∼25−/− mice and overexpressing Mycn induced MBs in the cortices of naïve recipient mice. In contrast, GNPs purified from the cerebella of P7 Ptch1+/−; miR-17∼92floxed/floxed; Nestin-Cre+ animals and overexpressing Mycn failed to induce tumors in recipient animals. Taken together, our findings demonstrate that the miR-17∼92 cluster is dispensable for cerebellar development, but required for SHH-MB development.
Inflammatory Ly6Chi monocytes and their conversion to M2 macrophages drive atherosclerosis regression

Atherosclerosis is a chronic inflammatory disease, and developing therapies to promote its regression is an important clinical goal. We previously established that atherosclerosis regression is characterized by an overall decrease in plaque macrophages and enrichment in markers of alternatively activated M2 macrophages. We have now investigated the origin and functional requirement for M2 macrophages in regression in normolipidemic mice that received transplants of atherosclerotic aortic segments. We compared plaque regression in WT normolipidemic recipients and those deficient in chemokine receptors necessary to recruit inflammatory Ly6Chi (Ccr2–/– or Cx3cr1–/–) or patrolling Ly6Clo (Ccr5–/–) monocytes. Atherosclerotic plaques transplanted into WT or Ccr5–/– recipients showed reduced macrophage content and increased M2 markers consistent with plaque regression, whereas plaques transplanted into Ccr2–/– or Cx3cr1–/– recipients lacked this regression signature. The requirement of recipient Ly6Chi monocyte recruitment was confirmed in cell trafficking studies. Fate-mapping and single-cell RNA sequencing studies also showed that M2-like macrophages were derived from newly recruited monocytes. Furthermore, we used recipient mice deficient in STAT6 to demonstrate a requirement for this critical component of M2 polarization in atherosclerosis regression. Collectively, these results suggest that continued recruitment of Ly6Chi inflammatory monocytes and their STAT6-dependent polarization to the M2 state are required for resolution of atherosclerotic inflammation and plaque regression.
A Combined Power M‐mode and Single Gate Transcranial Doppler Ultrasound Microemboli Signal Criteria for Improving Emboli Detection and Reliability

Single gate transcranial Doppler spectrogram (sgTCD) has a high variability in the detection of microembolic signals (MES), Adding Power M‐mode Doppler (PMD) information may improve MES detection. Our study's aim is to derive combined PMD/sgTCD microemboli criteria to overcome this limitation.
The neural basis of romantic love

The neural correlates of many emotional states have been studied, most recently through the technique of fMRI. However, nothing is known about the neural substrates involved in evoking one of the most overwhelming of all affective states, that of romantic love, about which we report here. The activity in the brains of 17 subjects who were deeply in love was scanned using fMRI, while they viewed pictures of their partners, and compared with the activity produced by viewing pictures of three friends of similar age, sex and duration of friendship as their partners. The activity was restricted to foci in the medial insula and the anterior cingulate cortex and, subcortically, in the caudate nucleus and the putamen, all bilaterally. Deactivations were observed in the posterior cingulate gyrus and in the amygdala and were right-lateralized in the prefrontal, parietal and middle temporal cortices. The combination of these sites differs from those in previous studies of emotion, suggesting that a unique network of areas is responsible for evoking this affective state. This leads us to postulate that the principle of functional specialization in the cortex applies to affective states as well.
Progression-free survival as a potential surrogate for overall survival in metastatic breast cancer

Background Progression-free survival (PFS) and time to progression (TTP) are frequently used to establish the clinical efficacy of anti-cancer drugs. However, the surrogacy of PFS/TTP for overall survival (OS) remains a matter of uncertainty in metastatic breast cancer (mBC). This study assessed the relationship between PFS/TTP and OS in mBC using a trial-based approach. Methods We conducted a systematic literature review according to the PICO method: ‘Population’ consisted of women with mBC; ‘Interventions’ and ‘Comparators’ were standard treatments for mBC or best supportive care; ‘Outcomes’ of interest were median PFS/TTP and OS. We first performed a correlation analysis between median PFS/TTP and OS, and then conducted subgroup analyses to explore possible reasons for heterogeneity. Then, we assessed the relationship between the treatment effect on PFS/TTP and OS. The treatment effect on PFS/TTP and OS was quantified by the absolute difference of median values. We also conducted linear regression analysis to predict the effects of a new anti-cancer drug on OS on the basis of its effects on PFS/TTP. Results A total of 5,041 studies were identified, and 144 fulfilled the eligibility criteria. There was a statistically significant relationship between median PFS/TTP and OS across included trials (r=0.428; P<0.01). Correlation coefficient for the treatment effect on PFS/TTP and OS was estimated at 0.427 (P<0.01). The obtained linear regression equation was ΔOS =−0.088 (95% confidence interval [CI] −1.347–1.172) + 1.753 (95% CI 1.307–2.198) × ΔPFS (R2=0.86). Conclusion Results of this study indicate a significant association between PFS/TTP and OS in mBC, which may justify the use of PFS/TTP in the approval for commercialization and reimbursement of new anti-cancer drugs in this cancer setting.
Reproductive pattern of the South American endemic shrimp Artemesia longinaris (Decapoda : Penaeoidea), off São Paulo State, Brazil

Sexual maturity, temporal reproductive pattern, and recruitment of juveniles were examined for the penaeoid shrimp Artemesia longinaris sampled for five and a half years in a tropical locality off the coast of Sao Paulo (23o S), Brazil. Monthly samples were taken from January 1998 to June 2003 at depths between 5 and 45 m. Ovarian maturity was used to examine breeding in adult females. Recruitment was defined as the percentage of juveniles of the total number of individuals in each month and season. A total of 10 288 females and 5 551 males were collected. Estimated sizes (carapace length) at the onset of sexual maturity were 11.0 mm and 13.4 mm for males and females, respectively. Over the five and a half years, females with ripe gonads were found in every season, with the highest percentages in summer (January-March). Juvenile shrimps occurred year-round. These results suggest a continuous reproduction of A. longinaris with temperature acting as an environmental stimulus for the duration of the ovary development cycle. These data and the hypothesis of the intrusion of the South Atlantic Central Water mass, which lowered water temperature and raised plankton production, sug- gest that the end of spring and the beginning of summer were the principal reproductive months. The classical paradigm of continuous reproduction at lower latitudes, with increased seasonality of breeding period at higher
Collapse of a Rotating Supermassive Star to a Supermassive Black Hole: Post-Newtonian Simulations

We study the gravitational collapse of a rotating supermassive star by means of a (3 + 1) hydrodynamic simulation in a post-Newtonian approximation of general relativity. This problem is particularly challenging because of the vast dynamic range in space that must be covered in the course of collapse. We evolve a uniformly rotating supermassive star from the onset of radial instability at Rp/M = 411, where Rp is the proper polar radius of the star and M is the total mass-energy, to the point at which the post-Newtonian approximation breaks down. We introduce a scale factor and a "comoving" coordinate to handle the large variation in radius during the collapse (8 ≲ Rp/M0 ≲ 411, where M0 is the rest mass) and focus on the central core of the supermassive star. Since T/W, the ratio of the rotational kinetic energy to the gravitational binding energy, is nearly proportional to 1/Rp for an n = 3 polytropic star throughout the collapse, the imploding star may ultimately exceed the critical value of T/W for dynamic instability to bar-mode formation. Analytic estimates suggest that this should occur near Rp/M ~ 12, at which point T/W ~ 0.27. For stars rotating uniformly at the onset of collapse, however, we do not find any unstable growth of bars prior to the termination of our simulation at Rp/M0 ~ 8. We do find that the collapse is likely to form a supermassive black hole coherently, with almost all of the matter falling into the hole, leaving very little ejected matter to form a disk. In the absence of nonaxisymmetric bar formation, the collapse of a uniformly rotating supermassive star does not lead to appreciable quasi-periodic gravitational wave emission by the time our integrations terminate. The coherent nature of the implosion, however, suggests that rotating supermassive star collapse will be a promising source of gravitational wave bursts. We also expect that, following black hole formation, long-wavelength quasi-periodic waves will result from quasi-normal ringing. These waves may be detectable by the Laser Interferometer Space Antenna.
A review of the nutritional value of legumes and their effects on obesity and its related co‐morbidities

Since the 1970s, the proportion of overweight and obese people in the United States has grown at an alarming rate. An awareness of the consequences of obesity on the health and well‐being of individuals is evident in the plethora of strategic plans at the local and national levels, most of which have largely fallen short of their goals. If interventions continue to be unsuccessful, it is estimated that approximately three of four Americans will be overweight or obese by 2020. Prevention of excess weight gain can be accomplished with relatively small changes in lifestyle behaviours to control body weight. Small sustainable changes are perhaps better than efforts to achieve larger changes that cannot be sustained. Legumes can be a valuable food by which the needs of the undernourished or under‐served populations could be met. They can be incorporated into meat products, such as sausages and burgers, to lower the energy density of these foods while providing important nutrients. Replacing energy‐dense foods with legumes has been shown to have beneficial effects on the prevention and management of obesity and related disorders, such as cardiovascular disease, diabetes and the metabolic syndrome. This review explores the nutritional value and obesity‐related health benefits of legume consumption while focusing on pulses.
Mismatched nucleotides as the lesions responsible for radiosensitization with gemcitabine: a new paradigm for antimetabolite radiosensitizers

Radiation sensitization by 2′,2′-difluoro-2′-deoxycytidine (dFdCyd) has correlated with dATP depletion [dFdCDP-mediated inhibition of ribonucleotide reductase (RR)] and S-phase accumulation. We hypothesized that radiosensitization by dFdCyd is due to nucleotide misincorporations in the presence of deoxynucleotide triphosphate pool imbalances, which, if not repaired, augments cell death following irradiation. The ability of dFdCyd to produce misincorporations was measured as pSP189 plasmid mutations in hMLH1-deficient [mismatch repair (MMR) deficient] and hMLH1-expressing (MMR proficient) HCT116 cells. Only MMR-deficient cells showed a significant increase in nucleotide misincorporations (2- to 3-fold increase; P ≤ 0.01) after radiosensitizing concentrations of dFdCyd ± 5 Gy radiation, which persisted for at least 96 h. dFdCyd (10 nmol/L) did not radiosensitize MMR-proficient HCT116 or A549 cells, but following small interfering RNA–mediated suppression of hMLH1, this concentration produced excellent radiosensitization (radiation enhancement ratios = 1.6 ± 0.1 and 1.5 ± 0.1, respectively; P < 0.05) and a 2.5-fold increase in mutation frequency in A549 cells. Cytosine arabinoside (1-β-d-arabinofuranosylcytosine), which can be incorporated into DNA but does not inhibit RR, failed to radiosensitize MMR-deficient cells or increase mutation frequency in the MMR-deficient and MMR-proficient cells. However, the RR inhibitor hydroxyurea radiosensitized MMR-deficient cells and increased nucleotide misincorporations (≥5-fold increase; P < 0.05), thus further implicating the inhibition of RR as the mechanism underlying radiosensitization by dFdCyd. These data showed that the presence and persistence of mismatched nucleotides is integral to radiosensitization by dFdCyd and suggest a role for hMLH1 deficiency in eliciting the radiosensitizing effect. [Mol Cancer Ther 2007;6(6):1858–68]
Oxygen Deprivation and the Cellular Response to Hypoxia in Adipocytes – Perspectives on White and Brown Adipose Tissues in Obesity

Relative hypoxia has been shown to develop in white adipose tissue depots of different types of obese mouse (genetic, dietary), and this leads to substantial changes in white adipocyte function. These changes include increased production of inflammation-related adipokines (such as IL-6, leptin, Angptl4, and VEGF), an increase in glucose utilization and lactate production, and the induction of fibrosis and insulin resistance. Whether hypoxia also occurs in brown adipose tissue depots in obesity has been little considered. However, a recent study has reported low pO2 in brown fat of obese mice, this involving mitochondrial loss and dysfunction. We suggest that obesity-linked hypoxia may lead to similar alterations in brown adipocytes as in white fat cells – particularly changes in adipokine production, increased glucose uptake and lactate release, and insulin resistance. This would be expected to compromise thermogenic activity and the role of brown fat in glucose homeostasis and triglyceride clearance, underpinning the development of the metabolic syndrome. Hypoxia-induced augmentation of lactate production may also stimulate the “browning” of white fat depots through recruitment of UCP1 and the development of brite adipocytes.
Multiple clear cell acanthomas.

In 1962, Degos et al 1 described an uncommon benign skin tumor, histologically identifiable by sharply demarcated, regular acanthosis. They named it clear cell acanthoma . Under microscopic examination, the tumor was found to consist of pale epidermal cells containing abundant amounts of glycogen, as evidenced by PAS-positive and diastase labile stains. Further clinical and histologic characterization followed publication of this report. 2,3 The acanthoma arises as an asymptomatic, single, erythematous papule or plaque, measuring 5 to 10 mm in diameter. It occurs in both sexes, usually in midlife. It most commonly appears on the lower part of the leg, especially on the calf. A fine, scaly layer may cover the tumor, which blanches on diascopy and bleeds easily with minor trauma, mimicking a pyogenic granuloma. The solitary clear cell acanthoma is an uncommon tumor. Multiple lesions, however, are truly rare, with only 12 cases reported to date. We report herein
Understanding e‐Government portal use in rural India: role of demographic and personality characteristics

Electronic government (e‐Government) is one of the most important ways to bridge the digital divide in developing countries. We develop a model of e‐Government portal use. We use various individual characteristics, namely demographics and personality, as predictors of e‐Government portal use. Specifically, our predictors were (1) gender, age, income and education; (2) the Big Five personality characteristics, i.e. extraversion, neuroticism, conscientiousness, agreeableness and openness to experience; and (3) personal innovativeness with information technology. We conducted a field study in a village in India. We collected data from over 300 heads of household. We found support for our model, with most variables being significant and explaining 40% of the variance in e‐Government portal use.
Interleukin-10 Release and Monocyte Human Leukocyte Antigen-DR Expression During Femoral Nailing

This study determined the effect of femoral nailing on the expression of monocyte Class II antigens and interleukin-10 release and sought to differentiate any differences in the release of these elements of immune reactivity in patients undergoing reamed and unreamed nailing. Thirty-two patients presenting with an acute femoral fracture were studied. In 15 patients, the femoral fracture was stabilized with a reamed technique and in 17 patients with an unreamed technique. Venous blood samples were taken at presentation, at anesthetic induction, immediately after nail insertion, and subsequently at 1, 4, and 24 hours and at 3, 5, and 7 days after surgery. Serum interleukin-10 was measured by an enzyme-linked immunosorbent assay, and monocyte human leukocyte antigen-DR expression was quantified by flow cytometry. Serum interleukin-10 release and human leukocyte antigen-DR expression on monocytes showed a clear response to the nailing procedure. The group of patients undergoing a reamed femoral nailing procedure showed significantly higher interleukin-10 release and a significant depression in the expression of human leukocyte antigen-DR on monocytes compared with those whose nail had been inserted unreamed. One patient in the reamed femoral nailing group died of adult respiratory distress syndrome 3 days after injury. Reamed intramedullary nailing appears to be associated with greater impairment of immune reactivity than is the unreamed nailing technique.
Outcome of patients with an indeterminate emergency department first-trimester pelvic ultrasound to rule out ectopic pregnancy.

OBJECTIVES Pelvic ultrasound performed by emergency physicians can identify a definite diagnosis in the majority of symptomatic first-trimester pregnant patients on the initial emergency department (ED) visit. However, a significant minority of such patients are diagnosed as having an indeterminate pregnancy state requiring further testing and consultation. The authors investigated the final outcome of patients with an initial indeterminate ED first-trimester pelvic ultrasound examination in the setting of an interdepartmental protocol to rule out ectopic pregnancy. METHODS This was an observational prospective cohort study performed at a regional, urban ED with more than 100,000 patient visits over a 13-month period. Pelvic ultrasound for first-trimester patients was prospectively performed by emergency physicians with gynecologic consultation for lack of intrauterine pregnancy (IUP) ultrasound findings. IUP was defined as a fundal gestational sac with either a yolk sac or a fetal pole. Pelvic ultrasounds were classified into diagnostic categories including definite IUP, embryonic demise, molar pregnancy, definite ectopic pregnancy, and indeterminate. For all patients with indeterminate pelvic ultrasound findings, final diagnostic categories and patient outcome were established by the use of patient records, obstetric ultrasound reports, laboratory studies, operative reports, and pathology reports. All patients with ectopic pregnancy were followed for mode of treatment. Descriptive statistics were calculated. RESULTS A total of 1,490 ED first-trimester pelvic ultrasound examinations were performed over 13 months establishing the following diagnostic rates for initial ED visit: IUP 1,037 (70%), demise 127 (8%), definite ectopic pregnancy 24 (2%), molar pregnancy 2 ( < 1%), and indeterminate 300 (20%). The 300 indeterminate patients were classified using the above protocol into the following final diagnostic categories: embryonic demise 158 (53%), IUP 88 (29%), ectopic pregnancy 44 (15%), and unknown outcome 10 (3%). Indeterminate patients with ectopic pregnancy were treated with methotrexate in 25 of 44 cases (57%) and surgically in 16 of 44 cases (36%); there were no laparotomies. In contrast, ectopic pregnancy patients diagnosed on initial ED visit were treated surgically in 20 of 24 cases (83%), including four laparotomies. CONCLUSIONS The outcome of symptomatic first-trimester patients with indeterminate ED pelvic ultrasounds is poor, with significantly high rates of embryonic demise and ectopic pregnancy. However, those indeterminate patients with the eventual diagnosis of ectopic pregnancy have a higher rate of medical methotrexate treatment and a reduced rate of invasive surgical treatment compared with ectopic pregnancy patients diagnosed at initial ED visit.