Miracle-dz/UniFAR-FTUs huggingface dataset:
Intensive Insulin Therapy Increases the Risk of Hypoglycemia in Neurocritical Care Patients

BackgroundIntensive insulin therapy protocols are widely used in intensive care medicine. A disadvantage of these protocols may be the occurrence of hypoglycemic episodes. Neurocritical care patients are particularly vulnerable to the effects of hypoglycemia. We aimed to study the risk of hypoglycemia in neurocritical care patients in relation to intensive insulin therapy. MethodsTo determine the effects of 2 different intensive insulin therapy protocols on glucose levels and hypoglycemia incidence, we collected data before and after implementation of the protocols in 2 university hospitals. The risk of hypoglycemia (blood glucose level below 3.0 mmol/L) was studied retrospectively with logistic regression analyses. ResultsIn hospital A, data were obtained on 152 patients before implementation of the protocol and on 649 patients after implementation of the protocol. In hospital B, data were obtained on 111 patients before implementation of the protocol and on 118 patients thereafter. Implementation of intensive insulin therapy protocols increased the time spent in the desired blood glucose range of 4.6 to 6.0 mmol/L in both hospitals, but increased the risk of hypoglycemia: the absolute risk of hypoglycemia during intensive care unit admission increased in hospital A from 14.5% to 20.3% (adjusted odds ratio=1.3; 95% confidence interval: 0.8-2.3) and in hospital B from 3.6% to 29.7% (adjusted odds ratio=28.6; 95% confidence interval: 5.9-138.9). ConclusionsImplementation of intensive insulin therapy protocols in neurocritical care patients not only seems to increase the time spent in the desired blood glucose range, but also seems to increase the risk of hypoglycemia. The risk of hypoglycemia strongly depends on characteristics of the intensive insulin therapy protocol.
Pathophysiology of Dyslipidemia in Cushing’s Syndrome

Dyslipidemia seems to be less frequent than other metabolic comorbidities in human Cushing’s syndrome. Nevertheless, it plays an important role in determining the global cardiovascular risk in overt and subclinical Cushing’s syndrome. In Cushing’s syndrome, there is an increase of triglyceride and total cholesterol levels whereas HDL can be at variable levels. Overt and subclinical Cushing’s syndrome share many features with metabolic syndrome including insulin resistance, abnormal fasting glucose levels, hypertension, obesity and dyslipidemia. The pathogenetic mechanisms are multifactorial, including direct and indirect cortisol action on lipolysis, free fatty acid production and turnover, very-low-density lipoprotein synthesis and fatty accumulation in the liver. AMP-activated protein kinase mediates many of glucocorticoid-induced metabolic changes. Insulin resistance plays a key role in determining lipid abnormalities. Other hormonal changes are involved including growth hormone, testosterone in men and estrogen in women, catecholamines and cytokines. In vitro, cortisol increases lipoprotein lipase in adipose tissues and particularly in visceral fat where lipolysis is activated, resulting in the release of free fatty acids into the circulation. The increase of free fatty acids may enhance the accumulation of hepatic lipids reducing glucose uptake and activating various serine kinases which results in decreased insulin signaling. Moreover, mice with a liver-specific disruption of the glucocorticoid receptor had diminished hepatic triglycerides levels. In humans, a high prevalence (up to 20%) of hepatic steatosis was also reported in patients with Cushing’s syndrome. Genetic variations in the glucocorticoid receptors may also affect the activity of cortisol, lipid metabolism and cardiovascular risk.
Use of Retrospective Continuous Glucose Monitoring for Optimizing Management of Type 2 Diabetes in India.

BACKGROUND Retrospective continuous glucose monitoring (CGM) studies may provide healthcare professionals (HCPs) with better understanding of glycemic patterns in patients with type 2 diabetes (T2D) and thereby support patient education and appropriate therapeutic interventions. METHODS Adults with T2D and A1C values between 8% and 10% were eligible for this 3-month study. Patients were scheduled for 5 visits that included baseline and a month-2 retrospective CGM study (iPro2, Medtronic) followed by data review and therapy modifications. A1C values were determined at baseline and at study end. Questionnaires were completed at each visit. HCP questionnaires assessed perception of the utility of studies; patient questionnaires assessed understanding of the importance of compliance with HCP recommendations. Indices of glycemic variability and control were calculated from CGM data retrospectively. RESULTS A total of 181 subjects enrolled and 148 completed the study (81.8%). There were no serious adverse device effects. Most subjects (91.2%) had > 1 therapy change after review of the first iPro2 test. Mean A1C decreased from 8.6% at baseline to 8.0% at month 3 (p<0.001). Questionnaire results from patients and HCPs indicated that both groups viewed the iPro2 studies and results as acceptable and useful. CGM-based glycemic variability metrics were similar in the two iPro2 tests. CONCLUSIONS iPro2 studies provided HCPs with insights and opportunities for initiating changes to treatment regimens and to diet and exercise behaviors, and provided patients with improved knowledge of the importance of therapy compliance. Favorable reductions in A1C suggest that iPro2 tests can facilitate optimal management of T2D.
Measures of Reliance and Compliance in Aided Visual Scanning

Objective: We study the dependence or independence of reliance and compliance as two responses to alarms to understand the mechanisms behind these responses. Background: Alarms, alerts, and other binary cues affect user behavior in complex ways. The suggestion has been made that there are two different responses to alerts—compliance (the tendency to perform an action cued by the alert) and reliance (the tendency to refrain from actions as long as no alert is issued). The study tests the degree to which these two responses are indeed independent. Method: An experiment tested the effects of the positive and negative predictive values of the alerts (PPV and NPV) on measures of compliance and reliance based on cutoff settings, response times, and subjective confidence. Results: For cutoff settings and response times, compliance was unaffected by the irrelevant NPV, whereas reliance depended on the irrelevant PPV. For subjective estimates, there were no significant effects of the irrelevant variables. Conclusion: Results suggest that compliance is relatively stable and unaffected by irrelevant information (the NPV), whereas reliance is also affected by the PPV. The results support the notion that reliance and compliance are separate, but related, forms of trust. Application: False alarm rates, which affect PPV, determine both the response to alerts (compliance) and the tendency to limit precautions when no alert is issued (reliance).
Cystathionine- γ-lyase promotes process of breast cancer in association with STAT3 signaling pathway

Here we provide evidences to link cystathionine-γ-lyase (CSE) to the development of breast cancer. CSE expression is up-regulated in both breast cancers and breast cancer cell lines and results in proliferation and migration of breast cancer cells. CSE Function in breast cancer depends on the STAT3 signaling pathway, a regulator of critical cell functions including cell growth in a wide variety of human cancer cells via activating the expression of relative genes. STAT3 positively relates to CSE expression. It activates the CSE promoter via a direct binding to the promoter. Moreover, CSE could reversely regulate STAT3 expression and consequently enhance the effect of STAT3 on CSE. Taken together, these data demonstrate for the first time the roles of CSE in breast cancer leading to breast cancer development in association with STAT3 signaling pathway.
Contribution of reactive oxygen species to pathways of quinolone-mediated bacterial cell death.

BACKGROUND Quinolone-mediated death of Escherichia coli has been proposed to occur by two pathways. One is blocked by inhibitors of protein synthesis; the other is not. It is currently unknown how these two pathways fit with the recent observation that hydroxyl radical accumulation is associated with quinolone lethality. METHODS E. coli was treated with thiourea plus 2,2'-bipyridyl to block hydroxyl radical accumulation, and the effect on quinolone lethality was measured for quinolones that distinguished the two lethal pathways: oxolinic acid requires protein synthesis to kill E. coli, while PD161144, a C-8-methoxy fluoroquinolone, does not. The lethal activity of another fluoroquinolone, moxifloxacin, was partially blocked by the presence of chloramphenicol, an inhibitor of protein synthesis. That feature made it possible to determine whether the effects of chloramphenicol and thiourea plus 2,2'-bipyridyl were additive. RESULTS Lethal activity of oxolinic acid was completely blocked by thiourea plus 2,2'-bipyridyl and by chloramphenicol. In contrast, PD161144 lethality was unaffected by these treatments. With moxifloxacin, both chloramphenicol and thiourea plus 2,2'-bipyridyl separately exhibited the same partial inhibition of quinolone lethality. No additivity in protection from moxifloxacin lethality was observed when thiourea, 2,2'-bipyridyl and chloramphenicol were combined and compared with the effect of chloramphenicol or thiourea plus 2,2'-bipyridyl used separately. CONCLUSIONS Inhibitor studies indicated that hydroxyl radical action contributes to quinolone-mediated cell death occurring via the chloramphenicol-sensitive lethal pathway but not via the chloramphenicol-insensitive pathway.
Oxidative stress contributes to the augmented exercise pressor reflex in peripheral arterial disease patients

• Peripheral arterial disease (PAD) is a common and debilitating condition linked with heightened risk of cardiovascular mortality. • Dynamic exercise elicits augmented blood pressure responses in PAD that could put the patient at risk for adverse event but the underlying mechanisms are unknown. • The exercise pressor reflex is comprised of group III and group IV muscle afferents that increase their discharge in response to mechanical and/or chemical stimulation. • In this study, we demonstrate that mechanically sensitive muscle afferents cause augmented reflex elevations in blood pressure during dynamic plantar flexion exercise in PAD. These responses occur prior to claudication pain, are related to disease severity and can be partly reduced by acute antioxidant infusion.
Collaborative incremental model development for an adaptive model-driven planning system

Military planners would benefit greatly from a planning system that dynamically incorporates real-world domain information, allowing plans to adapt easily to new information. The Joint Air Ground Unified Adaptive Replanning System (JAGUAR) system provides a model-driven planning paradigm for such a dynamic air mission planning domain. Developing models for this distributed and dynamic environment proved challenging, both for building models that were meaningful for all of the components and for creating models that could be fed in seamlessly to the running system. This paper gives an overview of the lessons learned during the six-year effort of developing adaptive models for the JAGUAR system.
Grain boundary separation in transgranular cleavage cracking

Abstract The energy balance associated with the transmission of cleavage front across high angle grain boundary is analysed theoretically. On the one hand, if the distance between adjacent break-through points is small, their crack trapping effect tends to be pronounced. On the other hand, decreasing this distance promotes the separation of persistent grain boundary areas. The effective grain boundary toughness is also dependent on the profiles of penetrating front sections and the surface free energy of grain boundary. The most energetically favourable crack front transmission mode can be reached through a self-adjusting process.
Phase III trial comparing doxorubicin plus cyclophosphamide with docetaxel plus cyclophosphamide as adjuvant therapy for operable breast cancer.

PURPOSE The combination of doxorubicin and cyclophosphamide (AC) is a standard adjuvant chemotherapy regimen. Studies of docetaxel and cyclophosphamide (TC) in metastatic breast cancer (MBC) showed promise in MBC. In 1997, we initiated a randomized adjuvant trial of TC compared with standard-dose AC with a primary end point of disease-free survival (DFS). PATIENTS AND METHODS Patients were eligible if they had stage I to III operable invasive breast cancer with complete surgical excision of the primary tumor. Between June 1997 and December 1999, 1,016 patients were randomly assigned to four cycles of either standard-dose AC (60 and 600 mg/m2, respectively; n = 510) or TC (75 and 600 mg/m2, respectively; n = 506), administered intravenously every 3 weeks as adjuvant chemotherapy. Radiation therapy (as indicated) and tamoxifen, for patients with hormone receptor-positive disease, were administered after completion of chemotherapy. RESULTS Both treatment groups (TC and AC) were well balanced with respect to major prognostic factors. Patients were observed through 2005 for a median of 5.5 years. At 5 years, DFS rate was significantly superior for TC compared with AC (86% v 80%, respectively; hazard ratio [HR] = 0.67; 95% CI, 0.50 to 0.94; P = .015). Overall survival rates for TC and AC were 90% and 87%, respectively (HR = 0.76; 95% CI, 0.52 to 1.1; P = .13). More myalgia, arthralgia, edema, and febrile neutropenia occurred on the TC arm; more nausea and vomiting occurred on the AC arm as well as one incident of congestive heart failure. CONCLUSION At 5 years, TC was associated with a superior DFS and a different toxicity profile compared with AC.
The Mechanism of Graft Rejection and the Concept of Antigenic Strength

‘It must be for almost ten years now that I have been stubbornly holding the view that the strength of transplantation antigens is essentially a direct function of the number of immunologically competent (antigen sensitive) cells which can recognize the antigen as foreign and react against it’. (Morten Simonsen, 1970 [13].)
Hypoxia-imaging with (18)F-Misonidazole and PET: changes of kinetics during radiotherapy of head-and-neck cancer.

BACKGROUND AND PURPOSE PET with (18)F-Misonidazole (FMISO-PET) is a non-invasive method for measuring tumor hypoxia. We analysed changes of FMISO-uptake during radiotherapy and their impact on patient outcome. MATERIALS AND METHODS Fourteen patients with HNC underwent repeated FMISO-PET prior to radiotherapy and after 30Gy. Dynamic and static PET-scans (2+4h p.i.) were acquired. FMISO-uptake was quantified by calculating standard uptake values (SUV) and tumor-muscle-ratios (TMR). Kinetic curve types representing tissue hypoxia were defined. Change of curve type was correlated with patient outcome. RESULTS The mean SUV 4h p.i. and the TMR decreased significantly during radiotherapy. SUV decreased clearly in 12/14 patients, and increased in 2 patients. TMR decreased in 11 patients, and increased in 3 patients. Prior to radiotherapy, three different shapes of kinetic curve types indicative for the degree of hypoxia could be defined in 12/14 patients: (1) accumulation type (severe hypoxia (n=8)), (2) intermediate type (intermediate degree of hypoxia (n=3)), and (3) wash-out type (low degree of hypoxia (n=1)). Curve type changed towards a lower degree of hypoxia at 30Gy in all but 3 patients. In three patients curve type remained unchanged. CONCLUSIONS The changes in tumor FMISO-uptake during radiotherapy indicate radio-induced reoxygenation.
Analysis of Gait Patterns in Normal School‐Aged Children

The continuing development of gait in 60 children aged 7–16 years was studied with plantar surface-attached transducers to describe the time pressure profiles of foot segments during stance. Decreased pronation/supination of the subtalar and midtarsal joints was shown by simultaneous onset and simultaneous peak on medial and lateral heel sensors. The resultant midstance showed a rapid lateral-to-medial loading of the forefoot. The foot-flat position with decreased rotation about the longitudinal axis of the foot persists even after the temporal parameters of gait attain mature values.
Interleukin-4 Inhibits Caspase-3 by Regulating Several Proteins in the Fas Pathway during Initial Stages of Human T Helper 2 Cell Differentiation*S

Interleukin-4 (IL-4) is the main cytokine that polarizes activated naïve CD4+ T cells in the T helper 2 (Th2) direction. IL-4 also regulates the subsequent stages of Th2 cell-mediated diseases, such as allergies. We conducted a proteomics study to identify IL-4-induced differences during the initial stages of T helper cell differentiation. Primary CD4+ T lymphocytes were isolated from human cord blood, activated through CD3 and CD28, and cultured in the presence or absence of IL-4. Soluble proteins were separated by two-dimensional electrophoresis and visualized by staining with autoradiography, which indicated that at least 20 proteins might be regulated by IL-4. From this minimum of 20 stained proteins, altogether 35 proteins were identified using tandem mass spectrometry. Interestingly the fragmented form of GDP dissociation inhibitor expressed in lymphocytes/Rho GDP dissociation inhibitor 2 (Ly-GDI), a known target of Caspase-3, was observed to be down-regulated in IL-4-treated cells. It was shown in further studies that IL-4 decreases Caspase-3 activity and cell death in these cells. Neutralizing Fas-Fas ligand interaction led to decreased Caspase-3 activity and lowered Ly-GDI fragmentation. We further characterized the effects of IL-4 on the expression of main regulators in the Fas-mediated pathway. We demonstrated that IL-4 decreases expression of Fas receptor and increases expression of Bid, Bcl-2, and Bcl-xL. Importantly IL-4 significantly up-regulated the short form of c-FLIP, although the levels of c-FLIP long were unaltered after IL-4 induction. Taken together, our results indicate that IL-4 inhibits caspase activity during the initial stages of human Th2 cell differentiation by regulating expression of several key players in the Fas-induced pathway.
Genetic variation at RYR1, IGF2, FUT1, MUC13, and KPL2 mutations affecting production traits in Chinese commercial pig breeds.

The identification of causative mutations affecting economically important traits has benefited the worldwide pig industry. We investigated the genetic variation at five loci including RYR1, IGF2, FUT1, MUC13, and KPL2 affecting traits related to production, reproduction, and disease resistance in a sample of 8009 pigs representing 3 commercial breeds (Duroc, Landrace, and Large White) from 28 farms in China. We found that all breeds, especially Duroc pigs, have high frequencies of favourable alleles for lean production and stress resist - ance at the IGF2 and RYR1 loci. However, all breeds have low frequencies of the diarrhea-resistant allele of FUT1, indicating that multigenerational selection is required for E. coli F18 + resistant pigs. No linkage disequilibrium was found between the RYR1 and FUT1 loci on pig chromosome 6, supporting the possibility of combined selec - tion for both F18 and stress-resistant pigs. Relatively high frequencies (> 0.5) of the MUC13 allele conferring resistance to E. coli F4ac were found in all three breeds with the highest frequency in Duroc pigs, suggesting that the breeders can establish F4ac diarrhea-resistant lines in a few generations. No defective allele at the KPL2 locus causing immotile short-tail sperms was found in Large White pigs of American, Canadian, Danish, English, and French origin, supporting the conclusion that the KPL2 defective allele is present exclusively in Finnish Large White pigs. These results provide useful information for pig breeding schemes in China.
A 2.45 GHz rectenna screen-printed on polycotton for on-body RF power transfer and harvesting

This paper presents a 2.45 GHz rectenna on textile for RF power transfer and harvesting. Thin 350 μm polycotton is used as a baseline flexible substrate and screen printing technique is used to map different layers. A 310 μm interface layer is first printed on both sides of polycotton in order to smooth its surface. Silver layer is then printed onto the interface layers to map the antenna and the rectifier layouts. The substrate is characterized over the 0.5-4.5 GHz frequency range using the two-line method. A relative permittivity of 3.23 and a loss tangent of 0.06 have been obtained at 2.45 GHz. A standard patch antenna matched to 50 Ω and a dual-polarization rectenna have been designed. Measurement of the return loss S11 of the patch antenna shows an excellent correlation with simulation results, thus indicating that the two-line characterisation is accurate. The performance of the polycotton antenna and rectenna is evaluated and compared with FR4. The measured radiation efficiency is 11% for the polycotton antenna, and 30% for the FR4 antenna. The polycotton rectenna generates 300 mV and 100 μW, 15 cm from a 100 mW EIRP transmitter.
Concurrent expression of recombination activating genes 1 and 2 in zebrafish olfactory sensory neurons

Each olfactory sensory neuron (OSN) expresses a single odorant receptor (OR) from a large repertoire of clustered OR genes. It has been hypothesized that OR gene regulation may involve stochastic DNA rearrangement, which in lymphocytes requires the recombination activating genes, rag1 and rag2. We have recently demonstrated that rag1 is expressed in zebrafish OSNs. Here we report that rag2, the obligate partner for rag1 function, is also expressed in OSNs and that its expression pattern mimics that of rag1. The onset of rag1 and rag2 expression preceded that of known zebrafish ORs and the number of rag1‐positive OSNs corresponded with the number expressing the olfactory cyclic nucleotide‐gated cation channel, an OSN marker. Zebrafish OSNs are the first example of concurrent rag expression in a nonlymphoid tissue. The expression of rag1 and rag2 in OSNs adds to the list of similarities between the olfactory and immune systems that includes monoallelic and mutually exclusive gene expression. genesis 29:156–162, 2001. © 2001 Wiley‐Liss, Inc.
Effect of human circumsporozoite antibodies in Plasmodium-infected Anopheles (Diptera: Culicidae).

Human circumsporozoite (CS) antibodies to Plasmodium falciparum were detected in blood meals from 45.0% of 1,547 field-collected Anopheles gambiae Giles sensu lato and Anopheles funestus Giles from western Kenya. Possible effects on malaria infections within the Anopheles host were investigated. Circumsporozoite antibodies were detected in blood meals up to 36 h after feeding. Antibodies crossing the midgut were detected experimentally in hemolymph from 4 to 36 h after feeding; human IgG also was present in hemolymph from fully gravid field-collected Anopheles. Ingestion of high-titer human CS antibodies or 2A10 monoclonal antibody to P. falciparum sporozoites by P. falciparum-infected An. gambiae, 10 d after feeding on an infected human, had no effect on oöcyst maturation, sporozoite rates, or sporozoite loads. Contact between CS antibodies and sporozoites in the hemocoel did not block sporozoite invasion of salivary glands. Human IgG antibodies were detected by an indirect fluorescent antibody technique on salivary gland sporozoites from 83.3% of 114 field-collected Anopheles. In 65.4% of 26 infections, antibodies persisted on sporozoites for at least three days. Thus, a high proportion of naturally infected An. gambiae s.l. and An. funestus in western Kenya transmit sporozoites that are bound with human IgG acquired during previous blood meals. The infectivity of such sporozoites needs to be determined in relation to natural transmission and to the potential use of malaria sporozoite vaccines.