bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence on nutritional therapy practice guidelines and implementation in adult critically ill patients: a scoping review protocol
Authors: Mooi Nomaxabiso M. , Ncama Busisiwe P. 
Published: November 2019

Abstract
Background
Nutritional therapy practice guidelines are designed to improve nutritional practices and thus the delivery of nutritional therapy in critically ill patients. However, they are not implemented despite the strong recommendation of nutritional therapy in the management of critical illness. The aim of this study is to map evidence on nutritional therapy guidelines and their implementation in critically ill adult patients.

Methods
Two independent reviewers will conduct a search of published scholarly and gray literature on the implementation of nutritional therapy guidelines in critically ill adults using Arksey and O’Malley’s scoping review framework. The search of studies will be conducted from databases such as PubMed, Google Scholar and EBSCOhost databases, Cumulative Index for Nursing and Allied Health Literature, MEDLINE, PsychINFO, PsychARTICLES, Health Source: Consumer Edition, Health Source: Nursing/Academic Edition, PreMEDLINE, Joanna Briggs Institute, and Cochrane Databases for Systematic Reviews. We will follow a predetermined criterion to map literature and additional articles will be searched from the reference lists of included studies. The Mixed Method Appraisal Tool (MMAT) will be used for quality assessment of the included studies. Quality assessment of included studies determines the overall quality of the resultant review.

Discussion
We hope to find studies on the implementation of nutritional therapy practice guidelines in adult critically ill patients and its impact on nutritional practices, patient outcomes, and health care costs. The results of this review will be disseminated through presentations in research seminars, conferences, and congresses and will also be available electronically and in print.

Systematic review registration
PROSPERO CRD42017058864
The impact of later eating rhythm on childhood adiposity: protocol for a systematic review
Authors: Zou Mengxuan , Northstone Kate , Perry Rachel , Johnson Laura , Leary Sam 
Published: November 2019

AbstractBackgroundChildhood adiposity has increased dramatically in the last few decades and is an important predictor of adulthood chronic disease. Later eating rhythm, termed night eating (NE), is increasingly prevalent in adults; however, the prevalence of NE in children and relationship between NE and adiposity in children still remains uncertain. The aim of this work is to review the association between adiposity in children and adolescents and NE, in terms of calorie intake, timing and meal frequency in the evening/night.MethodsThe Cochrane library, CINAHL, Embase, MEDLINE (via OVID) and Web of Science databases will be searched from inception to November 2019 for randomised controlled trials (RCTs) and observational studies (cohort, cross-sectional and case-control studies) which investigate the association between later vs. earlier timing of food intake at night or relatively more vs. less energy intake in any eating occasions or time period after 4 pm on adiposity in children and adolescents (4–18 years). The outcomes will be body mass index (BMI)/BMI standard deviation score (BMI-SDS or BMIZ-score), waist circumference (WC), fat mass index (FMI)/percentage of body fat (%BF) or waist to hip ratio (WHR). No language restriction will be applied. Screening for eligibility from the title and abstracts and data extraction from the full texts will be carried out by two reviewers independently. References listed in the included studies will be hand-searched for any additional articles. The quality of included RCT studies will be assessed using Revised Cochrane Risk of Bias tool (RoB 2), and of observational studies using Newcastle Ottawa scale. A qualitative synthesis of the results will be presented, and meta-analysis will be conducted, where appropriate.DiscussionThe planned systematic review will investigate the association between later eating rhythm and adiposity in children and adolescents. Understanding the best meal size, timing of energy intake and meal frequency across the evening time for maintaining healthy weight in children is important in order to give parents the best advice to help prevent adulthood obesity and associated chronic diseases in their children.Systematic review registrationPROSPEROCRD42019134187.
The feasibility of using smartphones and mobile breathalyzers to monitor alcohol consumption among people living with HIV/AIDS
Authors: Lauckner Carolyn , Taylor Erica , Patel Darshti , Whitmire Alexis 
Published: November 2019

AbstractBackgroundFor people living with HIV/AIDS (PLWHA), alcohol consumption is associated with poor treatment outcomes and medication adherence. This pilot study examined the feasibility of using smartphones and mobile Bluetooth breathalyzers for monitoring alcohol consumption among PLWHA (N = 17).MethodsFor 2 weeks, participants responded to twice-daily text message prompts by completing a breathalyzer reading and a mobile survey about their alcohol use. They also completed baseline questionnaires assessing alcohol consumption and hazardous drinking behaviors.ResultsParticipants completed an average of 22 of 28 breathalyzer readings and 17 of 28 mobile surveys, and were more likely to complete daytime (vs. evening) monitoring tasks. Results suggested that self-reported frequency of binge drinking at baseline was related to an increased number of days with alcohol consumption according to breathalyzer and mobile surveys, as well as a higher average blood alcohol content. Qualitative interviews found generally positive attitudes toward the technologies, but some participants reported experiencing technical difficulties.ConclusionsOverall, this preliminary research suggests that smartphone monitoring of alcohol consumption among PLWHA may reflect cross-sectional self-reported alcohol consumption behaviors, but could use improvements to increase adherence to monitoring tasks.
Hand hygiene compliance and associated factors among health care providers in Central Gondar zone public primary hospitals, Northwest Ethiopia
Authors: Engdaw Garedew Tadege , Gebrehiwot Mulat , Andualem Zewudu 
Published: November 2019

Abstract
Background
Poor hand hygiene compliance is one in all the leading contributory factors to healthcare-associated infections. This is an important source of complications across the continuum of care and poses a serious threat to people admitted to hospitals. However, the magnitude and associated factors of hand hygiene compliance in public primary hospitals were not well investigated in Ethiopia. Therefore, this study was conducted to assess hand hygiene compliance and associated factors among health care providers in Central Gondar Zone public primary hospitals, Northwest Ethiopia.

Methods
An Institutional based cross-sectional study was conducted from March to April 2019 among health care providers. The data were collected using self-administered questionnaires and observational checklists. Using Epi Info 3.1, data was entered and analyzed using SPSS version 23. The data were analyzed using descriptive statistics and logistic regression models. A p-value less than 0.05 with 95% confidence interval was used to declare statistical significance.

Results
Of 335 study participants, 50 (14.9%), had good hand hygiene compliance. Training on hand hygiene (AOR = 8.07, 95%CI: 2.91, 22.39), availability of adequate soap and water for hand hygiene (AOR = 5.10, 95%CI: 1.93, 13.52), availability of alcohol-based hand rub (AOR = 3.23, 95%CI: 1.32, 7.92), knowledge about hand hygiene (AOR = 6.74, 95%CI: 2.96, 15.34) and attitude towards hand hygiene (AOR = 2.15, 95%CI: 1.04, 4.46) were factors associated with hand hygiene compliance.

Conclusion
The overall level of hand hygiene compliance among health care providers was poor. Training, availability of adequate soap and water, availability of alcohol-based hand rub, knowledge on hand hygiene, and attitude of health care providers were significantly associated with hand hygiene compliance.
Association of Female Sexual Dysfunction and Fertility: a cross sectional study
Authors: Oindi Felix Mwembi , Murage Alfred , Lema Valentino Manase , Mukaindo Abraham Mwaniki 
Published: November 2019

Abstract
Background
Sexual function plays an essential role in the bio-psychosocial wellbeing and quality of life of women and disturbances in sexual functioning often result in significant distress. Female sexual dysfunction (FSD) and subfertility are common problems affecting approximately 43 and 20% of women respectively. However, despite the high prevalence of both conditions, little has been studied on the effects of subfertility on sexual functioning especially in sub-Saharan Africa. We set out to compare the prevalence of female sexual dysfunction in patients on assessment for sub-fertility and those either seeking or already on fertility control services at a private tertiary teaching hospital in Kenya.

Methods
This was an analytical cross sectional study. Eligible women of reproductive age (18–49 years), attending the gynaecological clinics with complaints of subfertility and those seeking fertility control services were requested to fill a general demographic tool containing personal data and the Female Sexual Function Index (FSFI) questionnaire after informed consent. Prevalence of sexual dysfunction was calculated as a percentage of patients not achieving an overall FSFI score of 26.55. Univariate and multivariate analysis were done to compare clinical variables to delineate the potential association.

Results
The prevalence of female sexual dysfunction was 31.2% in the subfertile group and 22.6% in fertility control group. The difference was not statistically significant (p = 0.187). The mean domain and overall female sexual function scores were lower in the subfertile group than the fertility control group though this was not statistically significant. The most prevalent sexual domain dysfunctions in both the subfertility and fertility control groups were desire and arousal while the least in both groups was satisfaction dysfunction. Subfertility type was not associated with sexual dysfunction. Higher education attainment was protective of female sexual dysfunction in the subfertile group while use of hormonal contraception was associated with greater sexual impairment in the fertility control group. On logistic regression analysis, higher maternal age and alcohol use appeared to be protective against sexual dysfunction.

Conclusion
The present study demonstrated no association between the fertility status and the prevalence female sexual dysfunction. Subfertility type was not associated with sexual dysfunction. Education level and hormonal contraception use were associated with female sexual dysfunction in the subfertile and fertility control groups respectively while alcohol use and higher maternal age appeared to be protective against sexual dysfunction.
Synergistic effect of reirradiation and PD-1 inhibitors in recurrent high-grade gliomas.
Authors: Iwamoto Fabio Massaiti , Donovan Laura , Schaff Lauren R. , Wang Tony J. C. , Lassman Andrew B. 
Published: November 2019

105 Background: To date, studies of single agent PD-1 or PDL-1 inhibitors in recurrent high-grade gliomas (HGG) have shown infrequent responses ( < 10%) and limited efficacy. Reirradiation is considered one of the standard salvage regimens for selected patients with recurrent gliomas but tumor responses are also infrequent ( < 5%). Radiotherapy counteracts the immunosuppressive tumor microenvironment by increasing MHC class I expression and enhancing tumor neoantigen presentation and has a significant synergistic effect with PD-1 inhibition in preclinical models of glioma. Methods: From December 2014 to June 2016, 20 patients (14 men, 6 women) with recurrent HGG were treated with the combination of reirradiation and PD-1 inhibitors. 18 patients had a glioblastoma, 1 anaplastic astrocytoma and 1 anaplastic oligodendroglioma. The median KPS at the start of this regimen was 70 (50 to 80). The median number of prior treatments for recurrent tumor was 2 (1-4), 100% had prior radaition, 95% prior temozolomide and 55% prior bevacizumab. 8 patients received pembrolizumab (2 mg/Kg every 3 weeks) and 12 patients received nivolumab (3 mg/Kg or 240 mg flat dose every 2 weeks). Median reirradiation dose was 35 Gy (12 Gy to 35 Gy). Results: There were 7 confirmed partial responses (35% objective response rate, ORR), 5 stable disease and 8 progressive disease. The median duration of response was 5 months (2.2 to 10+ months). Median PFS was 4 months and median OS was 10 months. Most common side effects were increased ALT (3 patients) and fatigue (2 patients). There was no obvious case of cerebral edema related to treatment. 5 patients required a mild increase of dexamethasone (2-4 mg) and all other 15 patients had decreased or stable dexamethasone dosage after the reirradiation. Conclusions: PD-1 inhibitors in combination with re-irradiation can be administered safely to patients with recurrent HGG. The ORR of 35% is an early signal of the potential synergist effect of the combination of PD-1 inhibitors with re-irradiation in HGG. This retrospective analysis of a heavily pre-treated population of recurrent HGG showed significantly higher ORR than either PD-1 inhibitors or re-irradiation alone. A clinical trial under development to test this hypothesis.
Survival of neuroblastoma patients treated by long-term infusion of anti-GD2 antibody ch14.18/CHO and killer-cell Ig-like receptor (KIR) genotypes and Fcγ-receptor polymorphisms.
Authors: Lode Holger N. , Loibner Hans , Troschke-Meurer Sascha , Valteau Couanet Dominique , Garaventa Alberto , Gray Juliet , Castel Victoria , Yaniv Isaac , Siebert Nikolai , Eger Christin , Juettner Madlen , Kietz Silke , Ehlert Karoline , Janzek Evelyne , Mueller Ina , Ladenstein Ruth 
Published: November 2019

111 Background: Receptors expressed on natural killer (NK) cells and their ligands on target cells involved in antibody-dependent cell-mediated cytotoxicity (ADCC) may influence outcome in patients (pts) with high-risk relapsed/refractory neuroblastoma (NB) treated by long-term infusion (LTI) of anti-GD2 antibody ch14.18/CHO Methods: 53 pts received 6x106 IU/m2 sc IL-2 (d1-5; 8-12), LTI of 100 mg/m2 ch14.18/CHO (d8-17) and 160 mg/m2 oral 13-cis-RA (d19-32) in a closed single center program (53 pts) (APN311-303). Polymorphisms in Fcγ-receptor genes 2A (H131R), -3A (V158F) and -3B (NA1/NA2), and KIR- as well as KIR ligand expression (HLA-C1; HLA-C2; HLA-Bw4+) were determined by real-time PCR. Results: The survival update of the APN311-303 cohort revealed a 5-y OS of 56.4±7.1% (mean OS 4.35y [0.3-6.2y]) and a 5-y PFS of 29.1±6.3% (mean PFS 2.4y [0.1 - 5.9y]). Median TTP/PFS was 1.35 y (95% CI: 0.21-2.48 y). This result is clearly superior to historical controls not treated with ch14.18/CHO with a 5-y OS of 14.8±6.8% (p < 0.005), indicating clinical efficacy of the treatment. In this cohort, we identified 26/53 pts with the NK- stimulatory KIR haplotype (2DS2+) who had superior OS- and PFS-rates compared to 18/53 pts with an inhibitory haplotype and KIR/KIR-ligand match (2DS2-, 3DL1+, Bw4+) (p < 0.02). Similarly, we found 33/53 pts with low affinity FCGR alleles (FCGR2A-H131R/R and/or FCGRA3A-V158 F/F). These patients showed lower PFS rates compared to 20/53 patients with high affinity FCGR polymorphisms (p < 0.01). ADCC analysis on day 15 of cycle 1 showed higher levels in the pt group with NK- stimulatory versus NK- inhibitory KIR/KIR ligand haplotypes (23±6 % vs. 6±2%, p < 0.01). A similar effect was observed in pts with high affinity FCGR polymorphisms with an ADCC increase of 20±6% compared to 11±2% in the low affinity FCGR control. Conclusions: KIR-haplotypes and FCGR- polymorphisms correlated with the functional immune parameter ADCC and clinical outcome, and thus support the relevance of ADCC for clinical efficacy of ch14.18/CHO in neuroblastoma.
Genome-wide, CRISPR-Cas9-based genetic screening for regulators of interferon-induced PD-L1 expression in AML cells.
Authors: Tse William T. , Bland Joshua B. 
Published: November 2019

116 Background: Expression of PD-L1 in AML cells is induced by pro-inflammatory signals, but how the induction is regulated is incompletely known. Genome-wide screening using the CRISPR-Cas9 technology could provide a strategy to interrogate the regulators of PD-L1 expression. Methods: A lentiviral CRISPR-Cas9 library, containing 3 sgRNA targeting each of 19,050 human genes (Nat Methods 2014, 11:783), was used to transduce THP-1 AML cells. Transduced cells were treated with IFN-γ and stained with an anti-PD-L1 antibody. Two subsets of cells were isolated by cell sorting according to their levels of PD-L1 expression. One subset consisted of cells that showed the median 5% of PD-L1 expression and the other subset, the lowest 5%. sgRNA integrated in the sorted subsets were amplified and their frequencies quantified by deep sequencing. Results: As expected, sgRNA targeting the PD-L1 gene itself were highly enriched in the subset that expressed a low level of PD-L1. sgRNA that targeted IFNGR2, β-chain of the IFN-γ receptor, were also enriched in this subset, whereas those for IFNGR1 were not. sgRNA targeting both JAK1 and JAK2 were enriched. By contrast, those for JAK3 and TYK2 were not. Enrichment was seen for sgRNA that targeted STAT1, a transcriptional activator downstream of JAK1/2, whereas sgRNA targeting the other STAT activators (STAT-2, 3, 4, 5A, 5B and 6) showed no enrichment. sgRNA targeting several serine kinases that regulate STAT1 phosphorylation (PKCδ, PKCε, PKCα, CAMKII, ERK, JNK, and CDK8) were not enriched. Nor were sgRNA targeting several phosphatases that modulate STAT1 activity (TC-PTP, PTPN1, SHP1 and SHP2). sgRNA targeting IRF1 (IFN regulatory transcription factor 1) were highly enriched, whereas sgRNA for IRF-2 to IRF-9 were not. In each of the affected genes, at least 2 out of the 3 sgRNA targeting the gene were enriched, indicating a generality of the findings. Conclusions: A CRISPR-Cas9-based screening strategy provided an unbiased interrogation of genes essential for PD-L1 expression on AML cells. It confirmed the importance of the IFNGR2-JAK1/2-STAT1-IRF1 axis, which could serve as targets for the development of drugs to suppress the ability of AML cells to evade host immunity.
The utility of molecular profiling in clinical trial enrollment and monitoring.
Authors: Hardison Matthew Thomas , Stover James 
Published: November 2019

12 Background: With the growing number of therapies that are directed against specific biomarkers, or discrete subsets of cancers, it is increasingly important to prospectively identify the most appropriate subjects for enrollment in a randomized, controlled clinical trial. Historically, clinical trial enrollment was strictly guided phenotypically. Subjects were included in a study simply based on presentation and disease progression, regardless of any underlying molecular mechanisms. Methods: Aegis involves the use of multiple molecular genetic procedures to investigate clinical trial subjects, whether for enrollment or disease monitoring. Fluorescent in situ hybridization (FISH) to detect chromosomal aberrations and single-gene Sanger sequencing are utilized to identify subjects with abnormalities associated with cancers such as chronic lymphocytic leukemia (CLL) prior to enrollment. Gene expression analysis using Nanostring digital RNA counting to stratify diffuse large B-cell lymphoma subjects, B-cell receptor clonal assessment through IgVH analyses, and next generation sequencing are also used to provide vital data throughout the clinical trial process. Results: The use of modern molecular genetic techniques increases and improves the data available to companies for subject enrollment, stratification, and monitoring throughout a clinical trial. Genetic analysis can indicate disease response through reduced mutation burden, changes in clonality of tumor cells, or a resolution of the underlying genetic cause. This data, in conjunction with clinical presentation is employed by pharmaceutical companies to design subsequent trial stages or identify additional potential disease states as targets for a particular therapeutic. Specifically, TP53 sequencing and FISH analysis in CLL are vital to assigning risk stratification to potential subjects. Conclusions: With the advent of immunotherapy and the precision nature of such therapeutic development, molecular profiling will continue to be a vital tool in the identification of optimal clinical trial subjects. This could ultimately lead to smaller, more definitive clinical trials, which would be helpful to clinicians and patients in terms of cost and time.
Preclinical assessment of PM21-particle expanded natural killer cells for ovarian cancer treatment.
Authors: Oyer Jeremiah , Gitto Sarah B. , Altomare Deborah , Lee Dean A. , Copik Alicja 
Published: November 2019

127 Background: Ovarian cancer has high recurrence rate and could benefit from immunotherapy with NK cells. A necessity for NK cell therapy is an efficient way to generate high doses of NK cells. The best method currently used in clinical trials is ex vivo NK cell expansion by co-culture with K562 CML cells, modified to express 41-BBL and membrane bound IL21 (K562.mb21). However feeder cell based methods are limited to ex vivo co-culture, difficult to disseminate, and not allowed in many jurisdictions. To overcome these limitations and to further improve NK cell therapy, we developed a feeder cell free particle based method for NK cell stimulation. These particles (PM21) are nano-scale, made from cell membranes of K562.mb21 cells, and efficiently stimulate NK cell expansion (mean 825 fold in 14 days, range 163–2216, n = 13). Methods: PM21 particles were prepared from K562.mb21 cells with a procedure developed by our group. NK cells were expanded by culturing CD3 depleted PBMCs with PM21 particles or by co-culture with K562.mb21 cells for 14 days as previously described. NSG mice ( ≥ 8 per group) were implanted ip with 1 x 106 SKOV3 ovarian tumor cells, seeded 8 days, and then treated with vehicle or NK cells expanded with PM21 or K562.mb21 cells (two doses of 10 x 106, injected 6 days apart), with or without in vivo administration of PM21 particles (600 µg, 3x weekly), and IL2 (25 KU, 3x weekly), all delivered ip. Survival analysis was performed with log rank (Mantel-Cox) test. Results: Treatment of SKOV3 engrafted NSG mice with NK cells, expanded with K562.mb21 cells or with PM21 particles, allowed significant ( < 0.0001) 10 day increase in survival compared to untreated animals that succumbed on average 21 days after start of treatment. Administration of ip PM21 particles enhanced survival by 5 days (p = 0.056) over no in vivo PM21 groups. Conclusions: NK cells prepared with PM21 particles or with K562.mb21 cells are equivalent in anti-SKOV3 efficacy and in vivo application of PM21 particles provides further benefit. Clinical translation is underway and clinical trials are being planned. PM21 particles can be the next step in development of NK cell therapy for enhancing both efficacy and dissemination of NK cell therapeutics for ovarian cancer.