Miracle-dz/UniFAR-FTUs huggingface dataset:
Insulin-Like Growth Factor-1 Levels in Term Newborns with Hypoxic–Ischemic Encephalopathy

Abstract Objective This study aims to evaluate the correlation of changes in serum insulin-like growth factor-1 (IGF-1) levels with the clinical staging of hypoxic–ischemic encephalopathy (HIE) in term newborns. Study Design A prospective study of 29 newborns with HIE (stage I = 15, stage II + III = 14) and 28 healthy term newborns as the control group was performed in the neonatal intensive care unit. IGF-1 levels were obtained within 6 hours after birth from HIE and control groups and again on day 3 from HIE group. HIE was classified using the Sarnat staging I to III. Results IGF-1 levels were significantly lower in the HIE group than in the control group (p = 0.024). It was lower in the HIE stage II to III group compared with HIE stage I group at birth (p < 0.0001) and on day 3 (p = 0.009). The mean IGF-1 levels were significantly higher on day 3 than on day 1 among stage II to III HIE (p = 0.006) and it was inversely correlated with staging (R = − 0.475, p = 0.009). There was a significant correlation between IGF-1 levels and Apgar score at 5 (R = 0.39, p = 0.042) and 10 minutes (R = 0.38, p = 0.035). Conclusions IGF-1 was lower in HIE and inversely correlated with clinical staging. It was increased with clinical improvement in the subsequent days.
Post‐Genome‐Wide Association Study Challenges for Lipid Traits: Describing Age as a Modifier of Gene‐Lipid Associations in the Population Architecture Using Genomics and Epidemiology (PAGE) Study

Numerous common genetic variants that influence plasma high‐density lipoprotein cholesterol, low‐density lipoprotein cholesterol (LDL‐C), and triglyceride distributions have been identified via genome‐wide association studies (GWAS). However, whether or not these associations are age‐dependent has largely been overlooked. We conducted an association study and meta‐analysis in more than 22,000 European Americans between 49 previously identified GWAS variants and the three lipid traits, stratified by age (males: <50 or ≥50 years of age; females: pre‐ or postmenopausal). For each variant, a test of heterogeneity was performed between the two age strata and significant Phet values were used as evidence of age‐specific genetic effects. We identified seven associations in females and eight in males that displayed suggestive heterogeneity by age (Phet < 0.05). The association between rs174547 (FADS1) and LDL‐C in males displayed the most evidence for heterogeneity between age groups (Phet = 1.74E‐03, I2 = 89.8), with a significant association in older males (P = 1.39E‐06) but not younger males (P = 0.99). However, none of the suggestive modifying effects survived adjustment for multiple testing, highlighting the challenges of identifying modifiers of modest SNP‐trait associations despite large sample sizes.
On the Value of Reptilian Brains to Map the Evolution of the Hippocampal Formation

Our ability to navigate through the world depends on the function of the hippocampus. This old cortical structure plays a critical role in spatial navigation in mammals and in a variety of processes, including declarative and episodic memory and social behavior. Intense research has revealed much about hippocampal anatomy, physiology, and computation; yet, even intensely studied phenomena such as the shaping of place cell activity or the function of hippocampal firing patterns during sleep remain incompletely understood. Interestingly, while the hippocampus may be a ‘higher order' area linked to a complex cortical hierarchy in mammals, it is an old cortical structure in evolutionary terms. The reptilian cortex, structurally much simpler than the mammalian cortex and hippocampus, therefore presents a good alternative model for exploring hippocampal function. Here, we trace common patterns in the evolution of the hippocampus of reptiles and mammals and ask which parts can be profitably compared to understand functional principles. In addition, we describe a selection of the highly diverse repertoire of reptilian behaviors to illustrate the value of a comparative approach towards understanding hippocampal function.
Initial testing (stage 1) of the notch inhibitor PF‐03084014, by the pediatric preclinical testing program

PF‐03084014, a γ‐secretase inhibitor, was tested against the PPTP in vitro cell line panel (1.0 nM to 10 μM) and against the in vivo xenograft panels (administered orally twice daily on Days 1–7 and 15–21). PF‐03084014 demonstrated limited in vitro activity, with no cell line achieving ≥50% inhibition. PF‐03084014 induced significant differences in EFS distribution in 14 of 35 (40%) solid tumor xenografts, and 1 of 9 ALL xenografts (which lacked a NOTCH1 mutation), but objective responses were not observed. PF‐03084014 demonstrated limited single agent activity in vitro and in vivo against the pediatric preclinical models studied. Pediatr Blood Cancer 2014; 61:1493–1496. © 2014 Wiley Periodicals, Inc.
Establishment of an international database for genetic variants in esophageal cancer

The establishment of a database has been suggested in order to collect, organize, and distribute genetic information about esophageal cancer. The World Organization for Specialized Studies on Diseases of the Esophagus and the Human Variome Project will be in charge of a central database of information about esophageal cancer–related variations from publications, databases, and laboratories; in addition to genetic details, clinical parameters will also be included. The aim will be to get all the central players in research, clinical, and commercial laboratories to contribute. The database will follow established recommendations and guidelines. The database will require a team of dedicated curators with different backgrounds. Numerous layers of systematics will be applied to facilitate computational analyses. The data items will be extensively integrated with other information sources. The database will be distributed as open access to ensure exchange of the data with other databases. Variations will be reported in relation to reference sequences on three levels––DNA, RNA, and protein—whenever applicable. In the first phase, the database will concentrate on genetic variations including both somatic and germline variations for susceptibility genes. Additional types of information can be integrated at a later stage.
An Effective Bundled Approach Reduces Surgical Site Infections in a High-Outlier Colorectal Unit

BACKGROUND: Surgical site infections are the most common hospital-acquired infection after colorectal surgery, increasing morbidity, mortality, and hospital costs. OBJECTIVE: The purpose of this study was to investigate the impact of preventive measures on colorectal surgical site infection rates in a high-volume institution that performs inherent high-risk procedures. DESIGN: This was a prospective cohort study. SETTINGS: The study was conducted at a high-volume, specialized colorectal surgery department. PATIENTS: The Prospective Surgical Site Infection Prevention Bundle Project included 14 preoperative, intraoperative, and postoperative measures to reduce surgical site infection occurrence after colorectal surgery. Surgical site infections within 30 days of the index operation were examined for patients during the 1-year period after the surgical site infection prevention bundle was implemented. The data collection and outcomes for this period were compared with the year immediately before the implementation of bundle elements. All of the patients who underwent elective colorectal surgery by a total of 17 surgeons were included. The following procedures were excluded from the analysis to obtain a homogeneous patient population: ileostomy closure and anorectal and enterocutaneous fistula repair. MAIN OUTCOME MEASURES: Surgical site infection occurring within 30 days of the index operation was measured. Surgical site infection–related outcomes after implementation of the bundle (bundle February 2014 to February 2015) were compared with same period a year before the implementation of bundle elements (prebundle February 2013 to February 2014). RESULTS: Between 2013 and 2015, 2250 abdominal colorectal surgical procedures were performed, including 986 (43.8%) during the prebundle period and 1264 (56.2%) after the bundle project. Patient characteristics and comorbidities were similar in both periods. Compliance with preventive measures ranged between 75% and 99% during the bundle period. The overall surgical site infection rate decreased from 11.8% prebundle to 6.6% at the bundle period (P < 0.001). Although a decrease for all types of surgical site infections was observed after the bundle implementation, a significant reduction was achieved in the organ-space subgroup (5.5%–1.7%; P < 0.001). LIMITATION: We were unable to predict the specific contributions the constituent bundle interventions made to the surgical site infection reduction. CONCLUSIONS: The prospective Surgical Site Infection Prevention Bundle Project resulted in a substantial decline in surgical site infection rates in our department. Collaborative and enduring efforts among multiple providers are critical to achieve a sustained reduction See Video Abstract at http://links.lww. com/DCR/A438.
Tissue-Specific Abundance of Regulatory T Cells Correlates with CD8+ T Cell Dysfunction and Chronic Retrovirus Loads1

Infection of mice with Friend virus induces the activation of CD4+ regulatory T cells (Tregs) that suppress virus-specific CD8+ T cells. This suppression leads to incomplete virus clearance and the establishment of virus persistence. We now show that Treg-mediated suppression of CD8+ T cells is tissue specific, occurring in the spleen but not the liver. Regardless of infection status, there was a 5-fold lower proportion of Tregs in the liver than in the spleen, much lower absolute cell numbers, and the relatively few Tregs present expressed less CD25. Results indicated that reduced expression of CD25 on liver Tregs was due to microenvironmental factors including low levels of IL-2 production by CD4+ Th cells in that tissue. Low CD25 expression on liver Tregs did not impair their ability to suppress CD8+ T cells in vitro. Correlating with the decreased proportion of Tregs in the liver was a significantly increased proportion of virus-specific CD8+ T cells compared with the spleen. The virus-specific CD8+ T cells from the liver did not appear suppressed given that they produced both IFN-γ and granzyme B, and they also showed evidence of recent cytolytic activity (CD107a+). The functional phenotype of the virus-specific CD8+ T cells correlated with a 10-fold reduction of chronic Friend virus levels in the liver compared with the spleen. Thus, suppression of CD8+ T cells by virus-induced Tregs occurs in a tissue-specific manner and correlates with profound effects on localized levels of chronic infection.
Effects of Pyrazinamide on Fatty Acid Synthesis by Whole Mycobacterial Cells and Purified Fatty Acid Synthase I

ABSTRACT The effects of low extracellular pH and intracellular accumulation of weak organic acids were compared with respect to fatty acid synthesis by whole cells of Mycobacterium tuberculosis and Mycobacterium smegmatis. The profile of fatty acids synthesized during exposure to benzoic, nicotinic, or pyrazinoic acids, as well as that observed during intracellular hydrolysis of the corresponding amides, was not a direct consequence of modulation of fatty acid synthesis by these compounds but reflected the response to inorganic acid stress. Analysis of fatty acid synthesis in crude mycobacterial cell extracts demonstrated that pyrazinoic acid failed to directly modulate the fatty acid synthase activity catalyzed by fatty acid synthase I (FAS-I). However, fatty acid synthesis was irreversibly inhibited by 5-chloro-pyrazinamide in a time-dependent fashion. Moreover, we demonstrate that pyrazinoic acid does not inhibit purified mycobacterial FAS-I, suggesting that this enzyme is not the immediate target of pyrazinamide.
A dose-dependent plasma signature of the safety and immunogenicity of the rVSV-Ebola vaccine in Europe and Africa

A specific plasma signature reveals the critical role of monocytes in the VSV-vectored Ebola vaccine immunogenicity and safety. Monocytes make their mark in Ebola vaccination A VSV-vectored Ebola vaccine was used in Guinea during the recent outbreak and has now been shown to be incredibly effective in preventing infection. However, the vaccine itself did cause somewhat severe reactions in some subjects, including fever and arthritis. Huttner et al. examined longitudinal plasma samples from vaccine recipients in Europe and Africa to identify a signature of the immune response and adverse events. The signature of monocyte-derived cytokines held true in both cohorts, suggesting that it could also be applied to other vaccine trials to determine immunogenicity and reactogenicity. The 2014–2015 Ebola epidemic affected several African countries, claiming more than 11,000 lives and leaving thousands with ongoing sequelae. Safe and effective vaccines could prevent or limit future outbreaks. The recombinant vesicular stomatitis virus–vectored Zaire Ebola (rVSV-ZEBOV) vaccine has shown marked immunogenicity and efficacy in humans but is reactogenic at higher doses. To understand its effects, we examined plasma samples from 115 healthy volunteers from Geneva who received low-dose (LD) or high-dose (HD) vaccine or placebo. Fifteen plasma chemokines/cytokines were assessed at baseline and on days 1, 2 to 3, and 7 after injection. Significant increases in monocyte-mediated MCP-1/CCL2, MIP-1β/CCL4, IL-6, TNF-α, IL-1Ra, and IL-10 occurred on day 1. A signature explaining 68% of cytokine/chemokine vaccine-response variability was identified. Its score was higher in HD versus LD vaccinees and was associated positively with vaccine viremia and negatively with cytopenia. It was higher in vaccinees with injection-site pain, fever, myalgia, chills, and headache; higher scores reflected increasing severity. In contrast, HD vaccinees who subsequently developed arthritis had lower day 1 scores than other HD vaccinees. Vaccine dose did not influence the signature despite its influence on specific outcomes. The Geneva-derived signature associated strongly (ρ = 0.97) with that of a cohort of 75 vaccinees from a parallel trial in Lambaréné, Gabon. Its score in Geneva HD vaccinees with subsequent arthritis was significantly lower than that in Lambaréné HD vaccinees, none of whom experienced arthritis. This signature, which reveals monocytes’ critical role in rVSV-ZEBOV immunogenicity and safety across doses and continents, should prove useful in assessments of other vaccines.
A systematic review and meta‐analysis of interval training versus moderate‐intensity continuous training on body adiposity

Interval training (including high‐intensity interval training [HIIT] and sprint interval training [SIT]) is promoted in both scientific and lay media as being a superior and time‐efficient method for fat loss compared with traditional moderate‐intensity continuous training (MICT). We evaluated the efficacy of HIIT/SIT when directly compared with MICT for the modulation of body adiposity. Databases were searched to 31 August 2016 for studies with exercise training interventions with minimum 4‐week duration. Meta‐analyses were conducted for within‐group and between‐group comparisons for total body fat percentage (%) and fat mass (kg). To investigate heterogeneity, we conducted sensitivity and meta‐regression analyses. Of the 6,074 studies netted, 31 were included. Within‐group analyses demonstrated reductions in total body fat (%) (HIIT/SIT: −1.26 [95% CI: −1.80; −0.72] and MICT: −1.48 [95% CI: −1.89; −1.06]) and fat mass (kg) (HIIT/SIT: −1.38 [95% CI: −1.99; −0.77] and MICT: −0.91 [95% CI: −1.45; −0.37]). There were no differences between HIIT/SIT and MICT for any body fat outcome. Analyses comparing MICT with HIIT/SIT protocols of lower time commitment and/or energy expenditure tended to favour MICT for total body fat reduction (p = 0.09). HIIT/SIT appears to provide similar benefits to MICT for body fat reduction, although not necessarily in a more time‐efficient manner. However, neither short‐term HIIT/SIT nor MICT produced clinically meaningful reductions in body fat.
A kinesin signaling complex mediates the ability of GSK-3β to affect mood-associated behaviors

Lithium has been the gold standard in the treatment of bipolar disorder (BPD) for 60 y. Like lithium, glycogen synthase kinase 3 (GSK-3) inhibitors display both antimanic-like and antidepressant-like effects in some animal models. However, the molecular mechanisms of both lithium and GSK-3 inhibitors remain unclear. Here we show that the GSK-3 inhibitor AR-A014418 regulated α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA)-induced GluR1 and GluR2 internalization via phosphorylation of kinesin light chain 2 (KLC2), the key molecule of the kinesin cargo delivery system. Specifically, AMPA stimulation triggered serine phosphorylation of KLC2 and, subsequently, the dissociation of the GluR1/KLC2 protein complex. This suggests that GSK-3 phosphorylation of KLC2 led to the dissociation of AMPA-containing vesicles from the kinesin cargo system. The peptide TAT-KLCpCDK, a specific inhibitor for KLC2 phosphorylation by GSK-3β, reduced the formation of long-term depression. Furthermore, the TAT-KLCpCDK peptide showed antimanic-like effects similar to lithium's on amphetamine-induced hyperactivity, a frequently used animal model of mania. It also induced antidepressant-like effects in the tail suspension and forced swim tests, two commonly used animal models of depression. Taken together, the results demonstrated that KLC2 is a cellular target of GSK-3β capable of regulating synaptic plasticity, particularly AMPA receptor trafficking, as well as mood-associated behaviors in animal models. The kinesin cargo system may provide valuable novel targets for the development of new therapeutics for mood disorders.
Pulmonary Eosinophils and Their Role in Immunopathologic Responses to Formalin-Inactivated Pneumonia Virus of Mice1

Enhanced disease is the term used to describe the aberrant Th2-skewed responses to naturally acquired human respiratory syncytial virus (hRSV) infection observed in individuals vaccinated with formalin-inactivated viral Ags. Here we explore this paradigm with pneumonia virus of mice (PVM), a pathogen that faithfully reproduces features of severe hRSV infection in a rodent host. We demonstrate that PVM infection in mice vaccinated with formalin-inactivated Ags from PVM-infected cells (PVM Ags) yields Th2-skewed hypersensitivity, analogous to that observed in response to hRSV. Specifically, we detect elevated levels of IL-4, IL-5, IL-13, and eosinophils in bronchoalveolar lavage fluid of PVM-infected mice that were vaccinated with PVM Ags, but not among mice vaccinated with formalin-inactivated Ags from uninfected cells (control Ags). Interestingly, infection in PVM Ag-vaccinated mice was associated with a ∼10-fold reduction in lung virus titer and protection against weight loss when compared with infected mice vaccinated with control Ags, despite the absence of serum-neutralizing Abs. Given recent findings documenting a role for eosinophils in promoting clearance of hRSV in vivo, we explored the role of eosinophils in altering the pathogenesis of disease with eosinophil-deficient mice. We found that eosinophil deficiency had no impact on virus titer in PVM Ag-vaccinated mice, nor on weight loss or levels of CCL11 (eotaxin-1), IFN-γ, IL-5, or IL-13 in bronchoalveolar lavage fluid. However, levels of both IL-4 and CCL3 (macrophage inflammatory protein-1α) in bronchoalveolar lavage fluid were markedly diminished in PVM Ag-vaccinated, PVM-infected eosinophil-deficient mice when compared with wild-type controls.
Direct and Indirect Effects of Psychological Distress on Stress-Induced Smoking.

OBJECTIVE Numerous studies have modeled the effects of stress in the laboratory, demonstrating that smokers who are exposed to experimental stressors exhibit significant increases in acute psychological distress. Whether these stress reactions are predictive of stress-induced smoking during an actual quit attempt, however, has not been examined. Furthermore, the possibility that such effects are particularly strong among smokers with higher ambient levels of distress has not been addressed. METHOD Nicotine-dependent smokers (N = 60; 40 women, 20 men) completed the Brief Symptoms Index (BSI) and then participated in a laboratory stress task 1 week before a quit attempt. Acute psychological distress was measured immediately before and after exposure to stressful and neutral stimuli. After they quit, participants completed a smoking diary for 14 days in which they recorded the degree to which their smoking was precipitated by emotional stress. RESULTS Consistent with our hypotheses, BSI scores predicted both exaggerated laboratory stress responses (p < .005) and smoking that was attributable to stress during the 14-day postquit period (p < .01). Laboratory stress reactions were predictive of stress-induced smoking (p < .01), and acute psychological stress reactions mediated the effects of BSI on stress-induced smoking. CONCLUSIONS Acute psychological stress reactivity is a potential mechanism underlying the effect of stress-induced smoking during a quit attempt.
Effect of depth on shear-wave elastography estimated in the internal and external cervical os during pregnancy

Abstract Aim: To investigate the effect of depth on cervical shear-wave elastography. Methods: Shear-wave elastography was applied to estimate the velocity of propagation of the acoustic force impulse (shear wave) in the cervix of 154 pregnant women at 11–36 weeks of gestation. Shear-wave speed (SWS) was evaluated in cross-sectional views of the internal and external cervical os in five regions of interest: anterior, posterior, lateral right, lateral left, and endocervix. Distance from the center of the ultrasound (US) transducer to the center of each region of interest was registered. Results: In all regions, SWS decreased significantly with gestational age (P=0.006). In the internal os, SWS was similar among the anterior, posterior, and lateral regions and lower in the endocervix. In the external os, the endocervix and anterior regions showed similar SWS values, lower than those from the posterior and lateral regions. In the endocervix, these differences remained significant after adjustment for depth, gestational age, and cervical length. SWS estimations in all regions of the internal os were higher than those of the external os, suggesting denser tissue. Conclusion: Depth from the US probe to different regions in the cervix did not significantly affect the SWS estimations.