Miracle-dz/UniFAR-FTUs huggingface dataset:
Liver abscess: contemporary presentation and management in a Western population.

AIM Historically, liver abscesses (LA) affected elderly, immunocompromised patients and were characterised by high morbidity and mortality, however there are no data pertaining to a New Zealand population with little information surrounding recent management trends. METHODS A retrospective review of demographic characteristics, clinical management and microbiological data on patients presenting with liver abscess between 2005-2014 was conducted. RESULTS Fifty-seven patients [37 males, median age 64 (range 15-87)] presented with LA and most patients were not comorbid. Ethnicity included European (47%), Chinese (16%) and Pacific Island (11%). Twenty-six patients had primary abscesses, 31 patients had secondary abscesses [biliary disease, appendicitis, diverticular disease]. Presenting symptoms were non-specific. Admission white cell count was raised in 50 (88%) of patients and 43 (75%) had a CRP≥200mg/L. All patients were investigated with CT scan with 34 LA located in the right lobe, 14 in the left and eight bi-lobar. Klebsiella pneumoniae was the commonest pathogen (26% of aspirates). Percutaneous drainage (PD) was used to treat 36 of 37 patients, 17 patients were treated with intravenous antibiotics alone and three patients required open drainage for loculated collections despite PD (n=1), intra-peritoneal rupture or sepsis (n=2). Thirteen patients were readmitted within 30 days for ongoing symptoms requiring intravenous antibiotics/further PD (9) or further investigations (4). The median PD duration was 10 days (range 3-53). Twenty-six patients required follow-up imaging over one month with 16 requiring follow-up over six weeks. CONCLUSION In a New Zealand setting, LA affect fit patients, and primary abscesses account for almost half of all presentation. PD is effective treatment in most LA although prolonged drainage and treatment with antibiotics may be necessary.
Noradrenergic activation of the basolateral amygdala maintains hippocampus-dependent accuracy of remote memory

Significance Emotional arousal creates lasting and vivid memories. According to the systems consolidation theory, the hippocampus has a time-limited role in memory, and retrieval of remote memories mainly relies on neocortical networks. Here we show that this systems consolidation and associated change in memory specificity constitute a dynamically regulated process that can be modified by emotional arousal status. Norepinephrine administration into the basolateral amygdala after an episodic-like training experience maintained accuracy and hippocampus dependency of remote memory. This altered systems consolidation was paralleled by time-regulated epigenetically driven transcriptional changes of memory-related genes in the hippocampus and neocortex. Emotional enhancement of memory by noradrenergic mechanisms is well-described, but the long-term consequences of such enhancement are poorly understood. Over time, memory traces are thought to undergo a neural reorganization, that is, a systems consolidation, during which they are, at least partly, transferred from the hippocampus to neocortical networks. This transfer is accompanied by a decrease in episodic detailedness. Here we investigated whether norepinephrine (NE) administration into the basolateral amygdala after training on an inhibitory avoidance discrimination task, comprising two distinct training contexts, alters systems consolidation dynamics to maintain episodic-like accuracy and hippocampus dependency of remote memory. At a 2-d retention test, both saline- and NE-treated rats accurately discriminated the training context in which they had received footshock. Hippocampal inactivation with muscimol before retention testing disrupted discrimination of the shock context in both treatment groups. At 28 d, saline-treated rats showed hippocampus-independent retrieval and lack of discrimination. In contrast, NE-treated rats continued to display accurate memory of the shock–context association. Hippocampal inactivation at this remote retention test blocked episodic-like accuracy and induced a general memory impairment. These findings suggest that the NE treatment altered systems consolidation dynamics by maintaining hippocampal involvement in the memory. This shift in systems consolidation was paralleled by time-regulated DNA methylation and transcriptional changes of memory-related genes, namely Reln and Pkmζ, in the hippocampus and neocortex. The findings provide evidence suggesting that consolidation of emotional memories by noradrenergic mechanisms alters systems consolidation dynamics and, as a consequence, influences the maintenance of long-term episodic-like accuracy of memory.
Coadministration of a tumor‐penetrating peptide improves the therapeutic efficacy of paclitaxel in a novel air‐grown lung cancer 3D spheroid model

Three‐dimensional (3 D) cell culture platforms are increasingly being used in cancer research and drug development since they mimic avascular tumors in vitro. In this study, we focused on the development of a novel air‐grown multicellular spheroid (MCS) model to mimic in vivo tumors for understanding lung cancer biology and improvement in the evaluation of aerosol anticancer therapeutics. 3 D MCS were formed using A549 lung adenocarcinoma cells, comprising cellular heterogeneity with respect to different proliferative and metabolic gradients. The growth kinetics, morphology and 3 D structure of air‐grown MCS were characterized by brightfield, fluorescent and scanning electron microscopy. MCS demonstrated a significant decrease in growth when the tumor‐penetrating peptide iRGD and paclitaxel (PTX) were coadministered as compared with PTX alone. It was also found that when treated with both iRGD and PTX, A549 MCS exhibited an increase in apoptosis and decrease in clonogenic survival capacity in contrast to PTX treatment alone. This study demonstrated that coadministration of iRGD resulted in the improvement of the tumor penetration ability of PTX in an in vitro A549 3 D MCS model. In addition, this is the first time a high‐throughput air‐grown lung cancer tumor spheroid model has been developed and evaluated.
Effects of context expectation on prospective memory performance among older and younger adults

ABSTRACT This experiment examined the impact of context expectation on prospective memory (PM) performance among older and younger adults. Participants responded to PM target words embedded in an ongoing lexical decision task (LDT). Older and younger adults performed similarly on the PM task. Regardless of age, PM was significantly better for participants in the correct context expectation condition and significantly worse in the incorrect context expectation condition relative to participants who held no expectations about the context in which targets would appear. Participants’ LDT response latencies were used to assess cost of the PM task to the ongoing task. Latencies were discernibly longer in the LDT block where the PM targets were expected compared to the block where they were not expected. The findings provide new information about how context can be used to support PM aging and suggest that contextual information can be equally beneficial for older and younger adults.
Histone H3 Lysine 4 Trimethylation, Lysine 27 Trimethylation, and Lysine 27 Acetylation Contribute to the Transcriptional Repression of Solute Carrier Family 47 Member 2 in Renal Cell Carcinoma

In recent years, finding effective biomarkers for identifying early stage cancer and predicating prognosis is crucial for renal cell carcinoma (RCC) diagnosis and treatment. In this study, a dramatic decrease of the solute carrier family 47 member 2 (SLC47A2) mRNA in RCC comparing with the paired adjacent nontumor tissues from patients at low Tumor Node Metastasis stage was observed. Thus, patients with SLC47A2 transcriptional repression are susceptible to RCC. Little is known about the regulation mechanism of SLC47A2. We found that it was a bivalent gene that was enriched with both histone H3 lysine 4 trimethylation (H3K4me3) and lysine 27 trimethylation (H3K27me3). Loss of mixed lineage leukemia 1 binding at the gene promoter caused decreased H3K4me3 enrichment and H3K4me3/H3K27me3 ratio, and subsequently repressed the expression of SLC47A2. These two epigenetic markers modulated the expression of SLC47A2 simultaneously, suggesting the regulation pattern for bivalent genes. Histone H3 lysine 27 acetylation also contributed to the expression of SLC47A2. An E2F1-histone deacetylase 10 complex catalyzed deacetylation of H3K27, then prevented the enrichment of H3K4me3, and finally reduced SLC47A2 expression. Consequently, the combined effect of all these factors determined SLC47A2 transcriptional repression in RCC tissues.
Extracellular translationally controlled tumor protein promotes colorectal cancer invasion and metastasis through Cdc42/JNK/ MMP9 signaling

The translationally controlled tumor protein (TCTP) can be secreted independently of the endoplasmic reticulum/Golgi pathway and has extrinsic activities when it is characterized as the histamine releasing factor (HRF). Despite its important role in allergies and inflammation, little is known about how extracellular TCTP affects cancer progression. In this study, we found that TCTP was overexpressed in the interstitial tissue of colorectal cancer (CRC) and its expression correlated with poor survival, high pathological grades and metastatic TNM stage in CRC patients. TCTP expression was greater in metastatic liver tissue than in primary tumors and was increased in highly invasive CRC cells. We demonstrated that the expression of TCTP was regulated by HIF-1α and its release was increased in response to low serum and hypoxic stress. Recombinant human TCTP (rhTCTP) promoted the migration and invasiveness of CRC cells in vitro and contributed to distant liver metastasis in vivo. Furthermore, rhTCTP activated Cdc42, phosphorylated JNK (p-JNK), increasing the translocation of p-JNK from the cytoplasm to the nucleus, as well as the secretion of MMP9. In addition, the expression of TCTP positively correlated with that of Cdc42 and p-JNK in clinical CRC samples. The silencing of Cdc42, JNK and MMP9 significantly inhibited the Matrigel invasion of rhTCTP-enhanced CRC cells. Collectively, these results identify a new role for extracellular TCTP as a promoter of CRC progression and liver metastases via Cdc42/JNK/MMP9 activation.
Contributions of Material Properties and Structure to Increased Bone Fragility for a Given Bone Mass in the UCD‐T2DM Rat Model of Type 2 Diabetes

Adults with type 2 diabetes (T2D) have a higher fracture risk for a given bone quantity, but the mechanisms remain unclear. Using a rat model of polygenic obese T2D, we demonstrate that diabetes significantly reduces whole‐bone strength for a given bone mass (μCT‐derived BMC), and we quantify the roles of T2D‐induced deficits in material properties versus bone structure; ie, geometry and microarchitecture. Lumbar vertebrae and ulnae were harvested from 6‐month‐old lean Sprague‐Dawley rats, obese Sprague‐Dawley rats, and diabetic obese UCD‐T2DM rats (diabetic for 69 ± 7 days; blood glucose >200 mg/dL). Both obese rats and those with diabetes had reduced whole‐bone strength for a given BMC. In obese rats, this was attributable to structural deficits, whereas in UCD‐T2DM rats, this was attributable to structural deficits and to deficits in tissue material properties. For the vertebra, deficits in bone structure included thinner and more rod‐like trabeculae; for the ulnae, these deficits included inefficient distribution of bone mass to resist bending. Deficits in ulnar material properties in UCD‐T2DM rats were associated with increased non‐enzymatic crosslinking and impaired collagen fibril deformation. Specifically, small‐angle X‐ray scattering revealed that diabetes reduced collagen fibril ultimate strain by 40%, and those changes coincided with significant reductions in the elastic, yield, and ultimate tensile properties of the bone tissue. Importantly, the biomechanical effects of these material property deficits were substantial. Prescribing diabetes‐specific tissue yield strains in high‐resolution finite element models reduced whole‐bone strength by a similar amount (and in some cases a 3.4‐fold greater amount) as the structural deficits. These findings provide insight into factors that increase bone fragility for a given bone mass in T2D; not only does diabetes associate with less biomechanically efficient bone structure, but diabetes also reduces tissue ductility by limiting collagen fibril deformation, and in doing so, reduces the maximum load capacity of the bone. © 2018 American Society for Bone and Mineral Research.
Brief Description of the McGill Paleoclimate Model ( MPM ) and Integration Scheme

[1] A coupled atmosphere-ocean-sea ice-land surface-ice sheet model of intermediate complexity, the so-called McGill Paleoclimate Model, is employed to study the response of the thermohaline circulation (THC) to various global climate coolings, which are realized by increasing the present-day planetary emissivity to various values. Generally, it is found that the response of the THC to global cooling is nonlinear: For a slightly cold climate the THC in the North Atlantic and the Pacific upwelling become intensified. For a very cold climate the THC in the North Atlantic may be weakened or even collapsed. The associated Pacific upwelling for a very cold climate also becomes weak when the THC is weakened, and intermediate deep water may form in the Pacific when the THC is collapsed. Some support for this nonlinear response is found in recent paleoceanographic data. The reduced atmospheric poleward moisture transport due to the global cooling is mainly responsible for the intensification of the THC in the North Atlantic for a slightly cold climate. For a very cold climate the global cooling may lead to a decrease of the meridional surface density gradient and an increase of the vertical density difference (lower layer density minus upper layer density) in the deep water formation region, which can weaken or shut down the THC. It is the temperature-dependent part of the density differences that is mainly responsible for the weakening or shutting down of the THC. The potential influence of surface temperature changes must be taken into account for a full understanding of the role of the THC in the climate system.
Effects of Skin Pigmentation on Pulse Oximeter Accuracy at Low Saturation

Background: It is uncertain whether skin pigmentation affects pulse oximeter accuracy at low HbO2 saturation. Methods: The accuracy of finger pulse oximeters during stable, plateau levels of arterial oxygen saturation (Sao2) between 60 and 100% were evaluated in 11 subjects with darkly pigmented skin and in 10 with light skin pigmentation. Oximeters tested were the Nellcor N-595 with the OxiMax-A probe (Nellcor Inc., Pleasanton, CA), the Novametrix 513 (Novametrix Inc., Wallingford, CT), and the Nonin Onyx (Nonin Inc., Plymouth, MN). Semisupine subjects breathed air-nitrogen-carbon dioxide mixtures through a mouthpiece. A computer used end-tidal oxygen and carbon dioxide concentrations determined by mass spectrometry to estimate breath-by-breath Sao2, from which an operator adjusted inspired gas to rapidly achieve 2- to 3-min stable plateaus of desaturation. Comparisons of oxygen saturation measured by pulse oximetry (Spo2) with Sao2 (by Radiometer OSM3) were used in a multivariate model to determine the interrelation between saturation, skin pigmentation, and oximeter bias (Spo2 − Sao2). Results: At 60–70% Sao2, Spo2 (mean of three oximeters) overestimated Sao2 (bias ± SD) by 3.56 ± 2.45% (n = 29) in darkly pigmented subjects, compared with 0.37 ± 3.20% (n = 58) in lightly pigmented subjects (P < 0.0001). The SD of bias was not greater with dark than light skin. The dark-light skin differences at 60–70% Sao2 were 2.35% (Nonin), 3.38% (Novametrix), and 4.30% (Nellcor). Skin pigment-related differences were significant with Nonin below 70% Sao2, with Novametrix below 90%, and with Nellcor at all ranges. Pigment-related bias increased approximately in proportion to desaturation. Conclusions: The three tested pulse oximeters overestimated arterial oxygen saturation during hypoxia in dark-skinned individuals.
INHIBITION OF CASPASE‐LIKE ACTIVITIES PREVENTS THE APPEARANCE OF REACTIVE OXYGEN SPECIES AND DARK‐INDUCED APOPTOSIS IN THE UNICELLULAR CHLOROPHYTE DUNALIELLA TERTIOLECTA 1

When the chlorophyte alga Dunaliella tertiolecta Butcher is placed in darkness, a form of programmed cell death with many similarities to apoptosis is induced, including the induction of caspase‐like proteases. Many uncertainties about the regulation and mediators that participate in the process remain. To examine the relationship between caspase‐like activities and different apoptotic events (i.e., phosphatidylserine [PS] translocation), increases in membrane permeability and numbers of dead cells revealed by SYTOX‐green staining, and the generation of reactive oxygen species (ROS), we used the broad‐range caspase inhibitor Boc‐D‐FMK to block the activity of the whole class of caspase‐like proteins simultaneously. In the presence of the inhibitor, ROS were not produced, and cells did not die. Loss of membrane asymmetry, indicated by external labeling of PS by annexin V, was apparent at midstages of light deprivation, although it did not conform to the typical pattern for PS exposure observed in metazoans or vascular plants, which occurs at early stages of the apoptotic event. Thus, we have evidence for a link between ROS and cell death involving caspase‐like enzymes in an alga. The fact that caspase‐like inhibitors prevent not only cell death, but also ROS and loss of cell membrane integrity and asymmetry, suggests that caspase‐like proteases might have regulatory roles early in cell death, in addition to dismantling functions.
Implementation and Operational Research: Population-Based Active Tuberculosis Case Finding During Large-Scale Mobile HIV Testing Campaigns in Rural Uganda

Background:Active tuberculosis (TB) screening outside clinics and in communities may reduce undiagnosed TB. Methods:To determine the yield of TB screening during community-based HIV testing campaigns (CHC) in 7 rural Ugandan communities within an ongoing cluster-randomized trial of universal HIV testing and treatment (SEARCH, NCT:01864603), we offered sputum microscopy to participants with prolonged cough (>2 weeks). We determined the number of persons needed to screen to identify one TB case, and the number of cases identified that linked to clinic and completed TB treatment. Results:Of 36,785 adults enumerated in 7 communities, 27,214 (74%) attended CHCs, and HIV testing uptake was >99%, with 941 (3.5%) HIV-infected adults identified. Five thousand seven hundred eighty-six adults (21%) reported cough and 2876 (11%) reported cough >2 weeks. Staff obtained sputum in 1099/2876 (38%) participants with prolonged cough and identified 10 adults with AFB-positive sputum; 9 new diagnoses and 1 known case already under treatment. The number needed to screen to identify one new TB case was 3024 adults overall: 320 adults with prolonged cough and 80 HIV-infected adults with prolonged cough. All 9 newly diagnosed AFB+ participants were linked to TB care within 2 weeks and were initiated TB treatment. Conclusions:In a rural Ugandan setting, TB screening as an adjunct to large-scale mobile HIV testing campaigns provides an opportunity to increase TB case detection.
Clinical course of sepsis in children with acute leukemia admitted to the pediatric intensive care unit*

Objective: To describe the clinical course, resource use, and mortality of patients with leukemia admitted to the pediatric intensive care unit with sepsis and nonsepsis diagnoses over a 10-yr period. Design: Retrospective analysis. Setting: Tertiary medical–surgical pediatric intensive care unit at C.S. Mott Children's Hospital, University of Michigan. Patients: All patients with leukemia admitted to the pediatric intensive care unit from January 1, 1998, to December 31, 2008. Interventions: None; chart review. Measurements and Main Results: Clinical course was characterized by demographics, leukemia diagnosis, phase of therapy, leukocyte count on admission, presence of sepsis, steroid administration, intensity of care, and Pediatric Risk of Mortality score on admission to the pediatric intensive care unit. The primary outcome was survival to pediatric intensive care unit discharge. Among 68 single admissions to the pediatric intensive care unit with leukemia during the study period, 33 (48.5%) were admitted with sepsis. Admission to the pediatric intensive care unit for sepsis was associated with greater compromise of hemodynamic and renal function and use of stress dose steroids (p = .016), inotropic and/or vasopressor drugs (p = .01), and renal replacement therapy (p = .028) than nonsepsis admission. There was higher mortality among children with sepsis than other diagnoses (52% vs. 17%, p = .004). Also, mortality among children with sepsis was higher among those with acute lymphoblastic leukemia (60% vs. 44%) compared with acute myelogenous leukemia. Administration of stress dose steroids was associated with higher mortality (50% vs. 17%, p = .005) and neutropenia. Patients with acute lymphoblastic leukemia and sepsis showed the greatest mortality and resource use. Conclusions: Patients with acute leukemia and sepsis had a much higher mortality rate compared with previously described sepsis mortality rates for the general pediatric intensive care unit patient populations. Patients who received steroids had an increased mortality rate, but given the retrospective nature of this study, we maintain a position of equipoise with regard to this association. Variation in mortality and resource use by leukemia type suggests further research is needed to develop targeted intervention strategies to enhance patient outcomes.
Impairment of 3000-m run time at altitude is influenced by arterial oxyhemoglobin saturation.

UNLABELLED The decline in maximal oxygen uptake (ΔVO(2)max) with acute exposure to moderate altitude is dependent on the ability to maintain arterial oxyhemoglobin saturation (SaO2). PURPOSE This study examined if factors related to ΔVO(2)max at altitude are also related to the decline in race performance of elite athletes at altitude. METHODS Twenty-seven elite distance runners (18 men and 9 women, VO(2)max = 71.8 ± 7.2 mL·kg(-1)·min(-1)) performed a treadmill exercise at a constant speed that simulated their 3000-m race pace, both in normoxia and in 16.3% O2 (∼2100 m). Separate 3000-m time trials were completed at sea level (18 h before altitude exposure) and at 2100 m (48 h after arrival at altitude). Statistical significance was set at P ≤ 0.05. RESULTS Group 3000-m performance was significantly slower at altitude versus sea level (48.5 ± 12.7 s), and the declines were significant in men (48.4 ± 14.6 s) and women (48.6 ± 8.9 s). Athletes grouped by low SaO2 during race pace in normoxia (SaO2 < 91%, n = 7) had a significantly larger ΔVO(2) in hypoxia (-9.2 ± 2.1 mL·kg(-1)·min(-1)) and Δ3000-m time at altitude (54.0 ± 13.7 s) compared with athletes with high SaO2 in normoxia (SaO2 > 93%, n = 7, ΔVO(2) = -3.5 ± 2.0 mL·kg(-1)·min(-1), Δ3000-m time = 38.9 ± 9.7 s). For all athletes, SaO2 during normoxic race pace running was significantly correlated with both ΔVO(2) (r = -0.68) and Δ3000-m time (r = -0.38). CONCLUSIONS These results indicate that the degree of arterial oxyhemoglobin desaturation, already known to influence ΔVO(2)max at altitude, also contributes to the magnitude of decline in race performance at altitude.