bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors associated with effective coverage of child health services in Burkina Faso
Authors: Koulidiati Jean‐Louis , De Allegri Manuela , Souares Aurelia , Ouedraogo Samiratou , Hien Hervé , Robyn Paul Jacob , Brenner Stephan 
Published: August 2018

SummaryObjectiveTo identify factors associated with both crude and effective health service coverage of under‐fives in rural Burkina Faso.MethodsIn a cross‐sectional study, 494 first‐line health facilities, 7347 households and 12 497 under‐fives were surveyed. Two sequential logistic random effects models were conducted to assess factors associated with crude and effective coverage.ResultsOf 614 children under‐five with a reported illness episode, 427 (69.5%) received care at a health facility. Of those, 274 (64.1%) received care at a health facility providing at least the minimum threshold of service quality. We found that younger age, having a severe illness, shorter distance between household and health facility, and being from wealthier households were positively associated with crude coverage. In addition, low patient caseload and longer consultation had a positive association, while frequent facility supervisions had a negative association with effective coverage. Moreover, the nurse to clinical staff ratio at the health facility was positively associated with both crude and effective coverage.ConclusionOur study found that crude coverage is associated with pre‐disposing and enabling factors of health care access, while the availability of nurses is a strong predictor for both crude and effective coverage. This suggests that in the context of scarcity of resources, investing in human resources in health sector could be one of the priorities for decision‐makers to ensure children in need not only access to healthcare but also good quality of care.
Synthetic colloid fluids (6% hydroxyethyl starch 130/0.4 and 4% succinylated gelatin) interfere with total plasma protein measurements in vitro
Authors: Yam Elodie , Hosgood Giselle , Rossi Gabriele , Smart Lisa 
Published: August 2018

BackgroundHigh molecular weight (MW) synthetic colloids interfere with refractometry. The effect of low MW synthetic colloids on refractometry is unknown.ObjectivesTo investigate the effect of 6% hydroxyethyl starch 130/0.4 (HES) and 4% succinylated gelatin (GELO) on the refractometric measurement of total plasma protein (TPP) and colloid osmotic pressure (COP) in canine plasma.MethodsHeparinized plasma from 10 dogs was diluted with 0.9% saline (NaCl), HES, and GELO in ratios of plasma:fluid, 9:1, 8:2, 7:3, 6:4, and 5:5. The biuret TPP (TPPb), refractometric TPP (TPPr), and COP assays were performed for all dilutions. Agreement (bias, 95% limits of agreement (LOA)) was tested between the TPPb (NaCl) and the TPPr of the NaCl, HES, and GELO plasma dilutions, and between the TPPb (NaCl) and the TPPb of the HES and GELO plasma dilutions.ResultsA small bias (0.06 g/dL, 95% LOA −0.51 to 0.39 g/dL) existed between TPPb (NaCl) and TPPr (NaCl). A large bias was found between TPPb (NaCl) and TPPr (HES) (1.38 g/dL, 95% LOA 0.30 to 3.10 g/dL), and TPPr (GELO) (1.18 g/dL, 95% LOA 0.53 to 2.88 g/dL). A small bias was found between TPPb (NaCl) and TPPb (HES) (0.08 g/dL, 95% LOA −2.04 to 2.20 g/dL), and a large bias was found between TPPb (NaCl) and TPPb (GELO) (1.00 g/dL, 95% LOA −0.59 to 2.60 g/dL). Increasing overestimation of TPPb (NaCl) by TPPr (HES and GELO) and TPPb (GELO) occurred with increasing colloid volumes.ConclusionsHES and GELO interfered with TPPr, and GELO also interfered with TPPb, in vitro. These variables should be interpreted with caution for dogs that have received these synthetic colloids.
Evaluation of end‐tidal carbon dioxide as a predictor of return of spontaneous circulation in dogs and cats undergoing cardiopulmonary resuscitation
Authors: Hogen Talli , Cole Steven G. , Drobatz Kenneth J. 
Published: August 2018

AbstractObjectiveTo determine whether the partial pressure of end‐tidal carbon dioxide (PetCO2) could predict return of spontaneous circulation (ROSC) in patients with cardiopulmonary arrest (CPA) undergoing CPR.DesignProspective observational study.SettingTwo private specialty referral hospitals.AnimalsThirty‐five client‐owned dogs and cats in CPA in which CPR was performed and pertinent data recorded on a purpose‐made form.InterventionsNone.Measurements and Main ResultsPetCO2was recorded at 1‐minute intervals during CPR. Hospital, animal, arrest, and outcome variables were also reported in the Utstein style where possible. Twelve animals (7 dogs and 5 cats) achieved ROSC; 4 of these (2 dogs and 2 cats) had sustained ROSC, of which 1 dog was discharged alive. Patients that achieved ROSC had significantly higher initial PetCO2(P= 0.0083), peak PetCO2(P< 0.0001), average PetCO2(P< 0.0001), and ΔPetCO2(difference between last and first recorded PetCO2;P= 0.0004) than patients not resuscitated. The PetCO2accurately discriminated between ROSC and failure to achieve ROSC at minutes 3, 4, 5, 6, 7, and 8 of CPR with area under the receiver operating characteristic curve of 0.926, 0.967, 0.938, 0.933, 0.956, and 1.00, respectively. The optimal cutoff PetCO2was 18 mm Hg (2.4 kPa), with a sensitivity of ≥80% and a specificity of ≥95% at minutes 3, 4, 5, 6, and 8, correctly classifying 91–100% of cases.ConclusionsThe results of this small study support previous recommendations to monitor PetCO2during CPR and suggest that PetCO2during CPR may be useful for determining the probability of ROSC. Absolute values and trends of PetCO2may assist clinicians and owners in making decisions for pets with CPA.
Antibiotic therapy of diabetic foot infections: A systematic review of randomized controlled trials
Authors: Tchero Huidi , Kangambega Pauline , Noubou Lazarre , Becsangele Beatrice , Fluieraru Sergiu , Teot Luc 
Published: August 2018

ABSTRACTDiabetic foot infection is a common diabetic complication that may end in lower limb amputation if not treated properly. We performed this systematic review to assess the clinical efficacy of different antibiotic regimens, whether systemic or topical, in the treatment of moderate to severe diabetic foot infections. We searched Medline, Web of Science, SCOPUS, Cochrane CENTRAL, and ScienceDirect for randomized controlled trials that evaluated the efficacy of antibiotic regimens in moderate to severe diabetic foot infections. The primary outcome of interest was the clinical efficacy (cure/improvement rates) of the regimens. We included 16 trials (4,158 patients) in this review, from which we extracted 10 comparisons: some trials compared systemic antibiotics to each other, others compared systemic to topical agents, while one study compared the combined topical and systemic agents to systemic antibiotics alone. Qualitative analysis of the findings of these studies showed that: (1) pipracillin/tazobactam was superior to ertapenem in severe infections (clinical resolution rate: 91.5% compared with PIP/TAZ 97.2%, p ≤ 0.04), but had similar efficacy in moderate infections, (2) ertapenem was more effective than tigecycline in moderate to severe infections (absolute difference −5.5, [95% CI −11.0, 0.1]), (3) the adjuvant use of topical agents with systemic antibiotics improved the outcomes, compared with systemic antibiotics alone (p = 0.024), (4) the rates of recurrence and re‐ulceration were significantly lower in patients using the amino‐penicillin regimen, compared with those using oral/intravenous ofloxacin, and (5) lower rates of complications accompanied the imipenem/cilastatin regimen, compared with the pipracillin/tazobactam regimen (p = 0.13). In conclusion, data from the included studies showed better results for ertapenem when compared with tigecycline; however, it was inferior to pipracillin/tazobactam in severe infections. The adjuvant use of topical agents improves the efficacy of systemic antibiotics in diabetic foot infection.
Neonatal gut and immune maturation is determined more by postnatal age than by postconceptional age in moderately preterm pigs
Authors: Ren Shuqiang , Hui Yan , Obelitz-Ryom Karina , Brandt Anne B. , Kot Witold , Nielsen Dennis S. , Thymann Thomas , Sangild Per T. , Nguyen Duc Ninh 
Published: August 2018

Preterm infants have immature organ functions that predispose them to gut and immune disorders. Developmental delays at preterm birth may affect various organs differently at term-corrected age. We hypothesized that gut and immune maturation in moderately preterm neonates depends more on birth and postnatal factors than on advancing postconceptional age (PCA). Using preterm pigs as models, we investigated how gut and immune parameters develop until term-corrected age and how these differ from those in term counterparts. Preterm ( n = 43, 106 days of gestation) and term pigs ( n = 41, 116 days of gestation) were delivered by caesarean section and euthanized at birth ( day 1) or postnatal day 11 (term-corrected age for preterm pigs) using identical rearing conditions. Relative to term pigs, preterm pigs had lower blood oxygenation, glucose, and cortisol levels, lower gut lactase activity, villus height, and goblet cell density, and lower blood neutrophil, helper T, and cytotoxic T cell numbers at birth. Despite slower growth in preterm pigs, most intestinal and immune parameters increased markedly after birth in both groups. However, some parameters remained negatively affected by preterm birth until postnatal day 11 (goblet cells, gut permeability, and cytotoxic T cells). The colon microbiota showed limited differences between preterm and term pigs at this time. At the same PCA, preterm 11-day-old pigs had higher blood leukocyte numbers and gut enzyme activities but lower villus height and blood cytotoxic T cell numbers relative to newborn term pigs. Birth and postnatal factors, not advancing PCA, are key determinants of gut and immune maturation in moderately preterm neonates. NEW & NOTEWORTHY Postnatally, preterm infants are often considered to reach a physiological maturation similar to that in term infants when they reach term-corrected postconceptional age (PCA). Using preterm pigs as models, we show that PCA may be a poor measure of gut and immune maturation because environmental triggers (regardless of PCA at birth) are critical. Possibly, PCA is only relevant to evaluate physiological maturation of organs that develop relatively independent of the external environment (e.g., the brain).
Absence of leptin signaling allows fat accretion in cystic fibrosis mice
Authors: Bederman Ilya R. , Pora Gavriella , O’Reilly Maureen , Poleman James , Spoonhower Kimberly , Puchowicz Michelle , Perez Aura , Erokwu Bernadette O. , Rodriguez-Palacios Alex , Flask Chris A. , Drumm Mitchell L. 
Published: August 2018

Negative energy balance is a prevalent feature of cystic fibrosis (CF). Pancreatic insufficiency, elevated energy expenditure, lung disease, and malnutrition, all characteristic of CF, contribute to the negative energy balance causing low body-growth phenotype. As low body weight and body mass index strongly correlate with poor lung health and survival of patients with CF, improving energy balance is an important clinical goal (e.g., high-fat diet). CF mouse models also exhibit negative energy balance (growth retardation and high energy expenditure), independent from exocrine pancreatic insufficiency, lung disease, and malnutrition. To improve energy balance through increased caloric intake and reduced energy expenditure, we disrupted leptin signaling by crossing the db/db leptin receptor allele with mice carrying the R117H Cftr mutation. Compared with db/db mice, absence of leptin signaling in CF mice (CF db/db) resulted in delayed and moderate hyperphagia with lower de novo lipogenesis and lipid deposition, producing only moderately obese CF mice. Greater body length was found in db/db mice but not in CF db/db, suggesting CF-dependent effect on bone growth. The db/db genotype resulted in lower energy expenditure regardless of Cftr genotype leading to obesity. Despite the db/db genotype, the CF genotype exhibited high respiratory quotient indicating elevated carbohydrate oxidation, thus limiting carbohydrates for lipogenesis. In summary, db/db-linked hyperphagia, elevated lipogenesis, and morbid obesity were partially suppressed by reduced CFTR activity. CF mice still accrued large amounts of adipose tissue in contrast to mice fed a high-fat diet, thus highlighting the importance of dietary carbohydrates and not simply fat for energy balance in CF.NEW & NOTEWORTHY We show that cystic fibrosis (CF) mice are able to accrue fat under conditions of carbohydrate overfeeding, increased lipogenesis, and decreased energy expenditure, although length was unaffected. High-fat diet feeding failed to improve growth in CF mice. Morbid db/db-like obesity was reduced in CF double-mutant mice by reduced CFTR activity.
The Effects of Cholesterol-Derived Oncometabolites on Nuclear Receptor Function in Cancer
Authors: Silvente-Poirot Sandrine , Dalenc Florence , Poirot Marc 
Published: August 2018

Abstract
Epidemiologic studies are controversial concerning the roles played by cholesterol in cancer risk and development, possibly as it is not cholesterol per se that is pathologic in cancers. Indeed, recent data reveal that the cholesterol metabolism in cancer cells can generate endogenous oncopromoter metabolites at higher levels compared with normal tissues and/or can be deregulated in the production of endogenous oncosuppressor metabolites in an opposite way. These metabolites are oxysterols, which are cholesterol oxygenation products generated by enzymatic and/or autoxidation processes. All these oxysterols are new classes of estrogen, glucocorticoid, or liver X nuclear receptor ligands, and their protumor action on their cognate receptors could explain some drug resistance, while treatment with antitumor metabolites could complement their deficiency in cancers and restore their action on their nuclear receptor. Given that hypercholesterolemia and high intakes of cholesterol-rich foods or processed foods can generate these oxysterols, their importance in cancer risk or development in overweight and obese people is to be considered. The discovery of these cholesterol-derived metabolites and the identification of the nuclear receptors mediating their pro- or antitumor activities are important findings, which should have major implications in the diagnosis, prevention, and treatment of different cancers and open new areas of research. Cancer Res; 78(17); 4803–8. ©2018 AACR.
Abstract A020: 5-Azacytidine primes AML cells for venetoclax-induced apoptosis by upregulating NOXA and PUMA protein expression
Authors: Jin Sha , Purkal Julie , Popovic Relja , Xiao Yu , Solomon Larry , Boghaert Erwin , Leverson Joel , Phillips Darren C. 
Published: August 2018

Abstract
Acute myeloid leukemia (AML) is a clonal hematologic malignancy characterized by complex heterogeneity and epigenetic features with an incidence of 20,830 new cases in 2015. Older patients, age ≥65 years, define a hard-to-treat population with a median overall survival (OS) of 2-8 months whose treatment options include induction chemotherapy, low-dose-Ara-C, best supportive care, and hypothemylating agents (HMAs). The HMA 5-Azacytidine (5-Aza) is an epigenetic targeting therapy that provides a median OS of 10.4 months in elderly AML patients (≥65 years of age; Dombret et al., 2015; Tamamyan et al., 2017). This antitumorigenic activity can be at least in part attributed to the induction of apoptosis since 5-Aza’s preclinical activity can be limited by members of the antiapoptotic BCL-2 protein family (Bogenberger et al., 2014). Venetoclax (ABT-199) is a highly selective, orally bioavailable BCL-2 inhibitor that is efficacious in numerous preclinical models of hematologic malignancies. A phase II clinical trial in heavily pretreated relapsed and refractory (R/R) AML patients has demonstrated venetoclax is active as a monotherapy (overall response rate (ORR) of 19%; Konopleva et al., 2016), providing the foundation for combinational studies with other antitumorigenic agents in AML. Early phase Ib clinical data in elderly AML patients (≥ 65 year of age) indicate that combining venetoclax with 5-Aza results in an ORR of 60-68% (Pratz et al., 2017). However, the underlying mechanism for the combinational activity observed between venetoclax and 5-Aza is unknown. Herein we report that 5-Aza upregulates the expression of the BH3-only proteins NOXA and PUMA in human AML cell lines. This is associated with an increase in the amount of NOXA and PUMA in complex with antiapoptotic BCL-2 proteins, serving to “prime” AML cells for induction of apoptosis by venetoclax treatment, and rationalizing the significant synergistic cell death observed when a panel of AML cell lines was treated with venetoclax and 5-Aza in vitro. Further, the venetoclax/5-Aza combination provided added benefit over either agent alone in two xenograft models of AML. Collectively these data provide a preclinical basis for an ongoing randomized phase III clinical trial evaluating venetoclax activity in combination with 5-Aza in treatment-naïve AML patients ineligible for standard induction therapy (M15-656, NCT02993523).
Citation Format: Sha Jin, Julie Purkal, Relja Popovic, Yu Xiao, Larry Solomon, Erwin Boghaert, Joel Leverson, Darren C. Phillips. 5-Azacytidine primes AML cells for venetoclax-induced apoptosis by upregulating NOXA and PUMA protein expression [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A020.
Abstract A133: Development of murine models to evaluate the impact of glucocorticoid receptor (GR) inhibition on chemotherapy response
Authors: Jahchan Nadine , Zhou Haiying , Stice James , Kong Wayne , McWeeney Dan , Sun Daqing , Rew Yosup , Du Xiaohui , Zhu Liusheng , Ye Qiuping , Jackson Erica L. , Fantin Valeria 
Published: August 2018

Abstract
The glucocorticoid receptor (GR) is a member of the nuclear receptor superfamily of ligand-activated transcription factors. GR is activated by its endogenous steroid hormone ligand, cortisol, and by synthetic glucocorticoid drugs such as dexamethasone. Several preclinical studies have established a role for GR in mediating resistance to both targeted therapies and conventional chemotherapies in epithelial cancers. Glucocorticoids have been reported to confer resistance to antimetabolites, taxanes, and platinum compounds in lung, prostate, bladder, renal, ovarian, and triple-negative breast cancers (Gassler et al., 2005; Li et al., 2017; Zhang et al., 2007). GR has also been reported to confer resistance to antiandrogen therapies in prostate cancer (Arora et al., 2013). Therefore, a molecule that inhibits GR activation could attenuate the development of resistance to cancer therapeutics. We are developing novel GR inhibitors that effectively block GR transcriptional activity in cells by competing for ligand binding and blocking GR-Coactivator interactions. In vitro, GR inhibition enhances the efficacy of chemotherapeutic agents under conditions supporting GR activation. In humans, the predominant glucocorticoid is cortisol, while in mice the predominant glucocorticoid is corticosterone (Siswanto et al., 2008). Corticosterone is a potent agonist of murine GR, but a weak agonist of human GR. When human tumor cells are grown in mice, GR is not active in the tumor cells due to the lack of circulating cortisol. Therefore it is necessary to provide exogenous cortisol to fully activate GR. Using xenograft models of ovarian and triple-negative breast cancer, we find that tumors grown in mice with physiologically relevant circulating cortisol levels are significantly less sensitive to standard-of-care chemotherapy than those grown in the absence of cortisol. Inhibition of GR is effective at restoring the response to chemotherapy in these models. These results demonstrate the therapeutic potential of GR inhibitors in combination with clinically utilized chemotherapeutics. Furthermore, the in vivo models developed provide a milieu for testing and developing GR inhibitors.
Citation Format: Nadine Jahchan, Haiying Zhou, James Stice, Wayne Kong, Dan McWeeney, Daqing Sun, Yosup Rew, Xiaohui Du, Liusheng Zhu, Qiuping Ye, Erica L. Jackson, Valeria Fantin. Development of murine models to evaluate the impact of glucocorticoid receptor (GR) inhibition on chemotherapy response [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A133.
Abstract A140: MERTK mediates intrinsic and adaptive resistance to AXL-targeting agents
Authors: McDaniel Nellie K. , Cummings Christopher T. , Brand Toni M. , Iida Mari , Hulse Justus , Pearson Hannah E. , Orbuch Rachel A. , Ondracek Olivia J. , Davies Kurtis D. , Gill Parkash , Wang Xiaodong , Frye Stephen V. , Earp H. Shelton , Kimple Randall J. , Harari Paul M. , DeRyckere Deborah , Graham Douglas K. , Wheeler Deric L. 
Published: August 2018

Abstract
The TAM family of receptor tyrosine kinases (RTKs) has been discovered to play a predominant role in promoting the growth, survival, and metastatic spread of several tumor types. AXL and MERTK are two TAM family RTKs that are overexpressed in head and neck squamous cell carcinoma (HNSCC), triple-negative breast cancer (TNBC), and non-small cell lung cancer (NSCLC), malignancies that are highly metastatic and lethal. The AXL receptor is the most well-characterized TAM receptor and has been found to mediate resistance to both conventional and targeted cancer therapies. Since AXL is overexpressed in aggressive tumor types, cancer patients are currently being enrolled in clinical trials testing AXL inhibitors. In the current study, we analyzed the efficacy of AXL inhibitors—both small molecule and monoclonal antibody therapy—in HNSCC, TNBC, and NSCLC preclinical models. We observed limited efficacy of anti-AXL targeting strategies across these different models, which was attributed to the upregulation of MERTK. MERTK was robustly overexpressed in cell lines and patient-derived xenografts treated with AXL inhibitors. Inhibition of MERTK sensitized HNSCC, TNBC, and NSCLC preclinical models to AXL inhibitors, leading to a more potent blockade of downstream signaling, decreased expansion of tumor cells in culture, and reduced tumor growth in vivo. Furthermore, ectopic overexpression of MERTK in AXL inhibitor-sensitive models resulted in resistance to AXL-targeting strategies. These results suggest that cotargeting both AXL and MERTK may be highly beneficial in a variety of tumor types where both receptors are expressed and may therefore prolong antitumor effects and improve the survival of patients with lethal malignancies.
Citation Format: Nellie K. McDaniel, Christopher T. Cummings, Toni M. Brand, Mari Iida, Justus Hulse, Hannah E. Pearson, Rachel A. Orbuch, Olivia J. Ondracek, Kurtis D. Davies, Parkash Gill, Xiaodong Wang, Stephen V. Frye, H. Shelton Earp, Randall J. Kimple, Paul M. Harari, Deborah DeRyckere, Douglas K. Graham, Deric L. Wheeler. MERTK mediates intrinsic and adaptive resistance to AXL-targeting agents [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A140.