bluuebunny/crossref_metadata_2025_split huggingface dataset:
IκB kinase 2 is not essential for platelet activation
Authors: Salzmann Manuel , Bleichert Sonja , Moser Bernhard , Mussbacher Marion , Haase Mildred , Hoesel Bastian , Schrottmaier Waltraud C. , Kral-Pointner Julia B. , Itakura Makoto , Schmidt Katy , Assinger Alice , Schmid Johannes A. 
Published: February 2020

Abstract
Platelets are small anucleate cells that release a plethora of molecules to ensure functional hemostasis. It has been reported that IκB kinase 2 (IKK2), the central enzyme of the inflammatory NF-κB pathway, is involved in platelet activation, because megakaryocyte/platelet-specific deletion of exons 6 and 7 of IKK2 resulted in platelet degranulation defects and prolonged bleeding. We aimed to investigate the role of IKK2 in platelet physiology in more detail, using a platelet-specific IKK2 knockout via excision of exon 3, which makes up the active site of the enzyme. We verified the deletion on genomic and transcriptional levels in megakaryocytes and were not able to detect any residual IKK2 protein; however, platelets from these mice did not show any functional impairment in vivo or in vitro. Bleeding time and thrombus formation were not affected in platelet-specific IKK2-knockout mice. Moreover, platelet aggregation, glycoprotein GPIIb/IIIa activation, and degranulation were unaltered. These observations were confirmed by pharmacological inhibition of IKK2 with TPCA-1 and BMS-345541, which did not affect activation of murine or human platelets over a wide concentration range. Altogether, our results imply that IKK2 is not essential for platelet function.
Fulminant central nervous system varicella-zoster virus infection unexpectedly diagnosed by metagenomic next-generation sequencing in an HIV-infected patient: a case report
Authors: Fang Mingxia , Weng Xing , Chen Liyun , Chen Yaling , Chi Yun , Chen Wei , Hu Zhiliang 
Published: February 2020

Abstract
Background
Varicella-zoster virus (VZV) infection can be diagnosed clinically once classical rash occurs but the diagnosis is challenging when typical rash is absent. We reported a case of fulminant central nervous system (CNS) VZV infection in a human immunodeficiency virus (HIV)-infected patient without typical VZV-related rash. CNS VZV infection was unexpected identified by metagenomic next-generation sequencing (mNGS).

Case presentation
A 28-year-old HIV-infected patient presented with neurological symptoms for 3 days. The patient, who was not suspected of VZV infection at admission, quickly progressed to deep coma during the first 24 h of hospitalization. An unbiased mNGS was performed on DNA extract from 300 μL cerebrospinal fluid (CSF) with the BGISEQ-50 platform. The sequencing detection identified 97,248 (out of 38,561,967) sequence reads uniquely aligned to the VZV genome, and these reads covered a high percentage (99.91%) of the VZV. Presence of VZV DNA in CSF was further verified by VZV-specific polymerase chain reaction and Sanger sequencing. Altogether, those results confirmed CNS VZV infection.

Conclusions
This study suggests that mNGS may be a useful diagnostic tool for CNS VZV infection. As mNGS could identify all pathogens directly from CSF sample in a single run, it has the promise of strengthening our ability to diagnose CNS infections in HIV-infected patients.
Prevalence and factors associated with intestinal parasitic infections among food handlers working at higher public University student’s cafeterias and public food establishments in Ethiopia: a systematic review and meta-analysis
Authors: Alemnew Birhan , Gedefaw Getnet , Alen Gedefaw Diress , Bizuneh Asmamaw Demis 
Published: February 2020

Abstract
Background
Intestinal infection is still an important public health problem in low-income countries. Food handlers may be infected by a wide range of enteropathogens and have been implicated in the transmission of many infections to the public. Therefore, the aim of this review was to produce the pooled prevalence and factors associated with intestinal parasitic infections among food handlers working at higher public University student’s cafeterias and public food establishments in Ethiopia.

Methods
Articles published in PubMed/Medline, Hinari, Web of Science, Science Direct, and Google Scholar were used using a search strategy. Observational studies (cross-sectional) revealing the prevalence and factors associated with intestinal parasitic infections at higher public University student’s cafeterias and public food establishments were incorporated. Meta-analysis was computed using STATA version 14 statistical software. Heterogeneity of the study was assessed using Cochrane Q test statistics and I2 test. The pooled prevalence of the intestinal parasitic infection and associated factors among food handlers was calculated by the random-effect model.

Results
Out of 138 reviewed studies, 18 studies were included to estimate the pooled prevalence of intestinal parasitic infections among food handlers in Ethiopia. All the eighteen articles were included in the analysis. This study revealed that the pooled prevalence of intestinal parasitic infections was 28.5% (95% CI: 27.4, 29.7). E. hystolitica /E. dispar complex 6.38 (95% Cl: 5.73, 7.04), A.lumbricodes 4.12 (95% Cl: 3.56, 4.67), and G. lamblia 3.12(95% Cl: 2.65, 3.60) were the most common intestinal parasitic infections in this study. Untrimmed fingernail 3.04 (95% CI: 2.19, 4.22), do not washing hands after defecation 2.71 (95% CI: 1.93, 3.82), do not washing hands after touching any body parts 2.41 (95% CI: 1.64, 3.56), do not made medical checkup 2.26 (95% CI: 1.57, 3.25), and do not receive food safety training 1.79 (95% CI: 1.30, 2.45) were factors significantly and positively associated with intestinal parasitic infections.

Conclusion
Parasitic infections among food handlers were significantly high. Untrimmed fingernail, do not washing hands after defecation, do not washing hands after touching any body parts, do not made regular medical checkup and do not receive food safety training were factors that increase the prevalence of intestinal parasitic infections.
Addressing ethnic disparity in antenatal care: a qualitative evaluation of midwives’ experiences with the MAMAACT intervention
Authors: Johnsen Helle , Ghavami Kivi Nazila , Morrison Cecilie H. , Juhl Mette , Christensen Ulla , Villadsen Sarah F. 
Published: February 2020

Abstract
Background
In Denmark, 13% of all children are born by non-Western immigrant women. The public antenatal care has not adapted to this increased diversity of women. Compared to women coming from Western countries, non-Western immigrant women have an increased prevalence of severe maternal morbidity and higher risks of maternal death, stillbirth and infant death. Suboptimal care is a contributing factor to these ethnic disparities, and thus the provision of appropriate antenatal care services is pivotal to reducing these disparities and challenges to public health. Yet, little is known about the targeted interventions which have been developed to reduce these inequities in reproductive health. The MAMAACT intervention, which included a training course for midwives, a leaflet and a mobile application, as well as additional visit time, was developed and tested at a maternity ward to increase responses to pregnancy warning signs among midwives and non-Western immigrant women. Aim: To explore the feasibility and acceptability of the MAMAACT intervention among midwives and identify factors affecting midwives’ delivery of the intervention.

Methods
Eight mini-group interviews with midwives (n = 18) were undertaken. Systematic text condensation was used to analyse data.

Results
Three main categories were identified, which were ‘Challenges of working with non-Western immigrant women’, ‘Attitudes towards and use of the leaflet and mobile application’, and ‘Organisational factors affecting the use of the MAMAACT intervention’.

Conclusions
The MAMAACT intervention was found to be feasible as well as acceptable among midwives. Women turning to relatives for pregnancy-related advice, time constraints during midwifery visits, incomplete clinical records and lack of professional interpreter assistance impacted midwives’ delivery of the MAMAACT intervention. Midwives displayed a readiness for the MAMAACT intervention; however, there is a need to further examine how contextual factors may impact the use of the intervention in antenatal care.

Trial registration
ClinicalTrials.gov, Retrospective Registration (07/2/2020), registration number NCT04261400.
Unrestricted prevalence of sedentary behaviors from early childhood
Authors: Azabdaftari Fariba , Jafarpour Parisa , Asghari-Jafarabadi Mohammad , Shokrvash Behjat , Reyhani Parvin 
Published: February 2020

Abstract
Background
Light and sedentary behaviors impose heavy challenges on societies. The objectives of this study are to identify child sedentary behaviors, and to examine the relationship between parent knowledge and behavioral style on children’s sedentary time in Iran.

Methods
This cross-sectional study was done among children and their parents selected randomly using multi-stage method, from 12 urban districts in Tabriz, Iran;2017. Data were collected through designing a multi-sectional questionnaire adopted from the Bjelland and previous studies to assess the time spent on sedentary behaviors among children/adolescents along with parent knowledge and behavioral style.

Results
From 480 children/adolescents and their parents 54.6% came from middle class families, and 55.62% were boys aged 2 to18. The percentage of time spent more than 120 min per day (min/d) on weekdays was for watching television (TV): (girls 24.4%, boys 21.0%), for playing computer and video games: (girls 38.7%, boys 54.7%), for electronic media communication (EMC): (girls 52.8%, boys 60.2%). The associated factors for watching TV: child age [12 years and above OR = 1.37; 95% CI = 0.53–3.54], parent knowledge [OR = 0.59, 95% CI = 0.35–0.99], and communicative styles [OR = 1.43, 95%CI = 1.11–1.86], and for playing computer and EMC: child age [5 years old and above OR = 4.83,95% CI =1.52–15.38, 12 years old and above OR = 13.76, 95% CI= 4.22–24.91], family socio-economic status [middle class OR = 2.52, 95% CI = 1.54–4.11, high class OR = 5.53, 95%CI = 1.80–15.89].

Conclusion
There is an urgent need to combat the unrestricted prevalence of sedentary behaviors among Iranian children/ adolescents who use computers and other electronic devices more than the recommended time every day from early childhood.
Parents should be provided with appropriate information about adverse effects of using electronic devices longer than recommended time by children. It is also essential to teach them beneficial communicative styles to monitor their children’s sedentary behaviors.
Testing for Mycobacterium tuberculosis infection using the QuantiFERON-TB GOLD assay in patients with comorbid conditions in a tertiary care endemic setting
Authors: Masood Kiran Iqbal , Jamil Bushra , Akber Alnoor , Hassan Maheen , Islam Muniba , Hasan Zahra 
Published: February 2020

Abstract
Introduction
There were 10 million new cases of tuberculosis (TB) in 2017. To eliminate TB, it is necessary to diagnose active TB and latent tuberculosis infection (LTBI). Diagnosis of paucibacillary disease and in extrapulmonary TB (EPTB) remains challenging; low mycobacterial load can be missed by microbiological or molecular based confirmation; EPTB, can be misdiagnosed due to absence of site specific specimens for testing. Interferon gamma release assays (IGRA) use T cell-based Interferon-gamma (IFN-γ) to identify infection with M. tuberculosis (MTB) but cannot discriminate between active and LTBI. We investigated how IGRA was being used in a high burden low resource setting.

Methods
We conducted a retrospective review of 149 consecutive cases received for QuantiFERON-TB Gold In-Tube Assay (QFT-GIT) testing in routine clinical service.

Results
Fifty-six cases were QFT-GIT positive and 93 were QFT-GIT negative. Thirty-six per cent of QFT-GIT tested cases had active TB. Of QFT-GIT positive cases, 59% patients had active TB; 10 with pulmonary and 23 with extra-pulmonary TB. The remaining 41% QFT-positive cases were LTBI. Of the QFT-GIT negative cases, 22% had active TB. Co-morbid conditions were present in 37% of QFT-GIT positive and 60% of QFT-GIT negative cases.

Conclusions
Our study shows that IGRA is being used as an adjunct test for active TB in this population. It highlights the complexity of interpreting QFT-GIT results particularly for QFT-GIT negative cases when ruling out MTB infection.
Single-tree influence of Tectona grandis Linn. f. on plant distribution and soil characteristics in a planted forest
Authors: Ikhajiagbe Beckley , Ogwu Matthew Chidozie , Lawrence Adebayo Emmanuel 
Published: February 2020

Abstract
Background
Little is known about the single-tree influence of Tectona grandis Linn. f. on plant distribution and soil characteristics in Benin City, Nigeria. We investigated the possible single-tree effect of T. grandis on understory plants in an 8-year-old teak plantation at the Moist Forest Research Station. An area of 36.57 m by 60.96 m was marked out and divided into 15 equal-sized subplots containing 10 trees per subplot. Marked distances from the base of a randomly selected tree per subplot were made (0–0.5 m, 0.5–1.0 m and 1.0–1.5 m).

Results
Single-tree influence of T. grandis was observed in the soil total organic carbon, total nitrogen and soluble phosphorus, where concentrations were higher with 1.5-m radius from the tree than beyond. Moreover, the pH of the topsoil within 1.5 m from the base of the tree was lower (pH 4.4) than beyond 1.5 m from the base of the tree (pH 5.4). Species-specific single-tree effect was also observed on the understory plant distribution likely due to diverse ecophysiological interactions. Within 1.5 m from the tree, plant species abundance, especially of Sida garckeana, Reisantia indica, Momordica charantia and Tridax procumbens were negatively affected. However, the distribution of Eleusine indica around the tree was not negatively influenced. Plant abundance was generally suppressed in Cynodon dactylon, Axonopus compressus, Andropogon gayanus, Commelina diffusa and Euphorbia hirta. Generally, there were more plant species beyond the canopy fringes than within the canopy, indicating inhibitory single-tree effects.

Conclusion
Not all plant species in close proximity to T. grandis are affected. This is important considering that plant-plant associations affect the quality of forest soils. Generally, more plant species were recorded outside the 1.5-m demarcation than within, an increase in soil organic matter may further enhance such plant species abundance. The impact of T. grandis in forest soil quality is possibly a factor of the outcome of its association with neighbouring plant species. Diverse mechanisms at play may be responsible for the observed effects on soil chemistry. However, a reduction in the soil organic matter and variations in other environmental factors also contributed to observed single-tree effect.
Planning of Food-Energy-Water-Waste (FEW2) nexus for sustainable development
Authors: Feng Bowen , van Dam Koen H. , Guo Miao , Shah Nilay , Passmore Stephen , Wang Xiaonan 
Published: February 2020

AbstractIt is critical for reliable infrastructure planning to address the Food-Energy-Water-Waste (FEW2) nexus at system level. This paper presents the applicability of resilience.io platform across water, energy and waste sectors (including food and agricultural waste) with focus on waste-to-energy pathway, aiming to establish the optimal FEW2 nexus based on economic and environmental indicators. A rich array of technology options, including water production facilities, clean energy technologies and waste-to-energy conversions are evaluated to meet the demand of water and energy (mainly gas and electricity), and the treatment requirement of waste and wastewater. A case study of Hunter Region, the largest region in Australia, is presented in this study, featuring the supply and demand context of developed countries. A full set of scenarios, including business-as-usual (BAU), water and wastewater, power plant decommission, waste-to-energy and policy intervention, is created to present FEW2 nexus from the perspective of individual nodes and the whole system. The results signal the benefits of biogas and syngas generation from anaerobic digestion and gasification for waste-to-energy pathway, alongside findings in water and energy sectors. The outcome of this analysis can then form the foundation of regional planning involving relevant stakeholders, with the modelling tools supporting scenario evaluation and collaborative learning to reach consensus in view of different performance indicators including financial and environmental metrics.
Awareness of analgesics complications in Saudi Arabia: a cross-sectional study
Authors: Siddig Amal I. , Alqahtani Abdulhadi M. , AlShalawi Alia , Turkistani Marwah , Binbaz Sarah , Altowairqi Amal 
Published: February 2020

Abstract
Background
All over the world, analgesics are considered one of the most widely used and abused medications. Painkillers such as paracetamol (acetaminophen), non-steroidal anti-inflammatory drugs (NSAIDs), and aspirin currently represent the principal means of pain management. Unfortunately, paracetamol and NSAIDs have dangerous side effects primarily when they are used improperly and without respect to safety rules. This study aims to assess the awareness of the indications, complications, and contraindications of commonly used analgesics.

Results
A total of 1554 participants responded to the survey, and the findings indicated that the main analgesic used is paracetamol. A proportion of 68.1% of the total number of respondents received their information about analgesic medications from a physician or pharmacist; 95.7% used analgesics when needed, and 70.9% mentioned that they would consult a physician or pharmacist if the pain was not relieved after the use of over-the-counter medications. Nearly 29% were not aware of the possibility of adverse effects of analgesic use.

Conclusion
The most commonly used analgesic is paracetamol, and most of the participants had a poor level of awareness regarding the complications and side effects of analgesics in general. Our recommendation is to conduct a continuous health education campaign about the use of analgesics.
Targeting NFE2L2/KEAP1 mutations in advanced NSCLC with the TORC1/2 inhibitor TAK-228.
Authors: Paik Paul K. , Ahn Linda Su Hyun , Ginsberg Michelle S. , Plodkowski Andrew J. , Kim Rachel , Doyle L. Austin , Rudin Charles M. 
Published: February 2020

9085 Background: Despite efforts over the past decade, no targeted therapy options exist for SQCLC pts. We have identified a heretofore untargeted oncogene (NFE2L2)/tumor suppressor (KEAP1) pair, each mutated in ~20% of patients with SQCLC. NFE2L2 encodes Nrf2, a transcription factor involved in the oxidative stress response which is targeted for degradation by Keap1. NFE2L2 mutations occur exclusively in an exon 2 hotspot that encodes the Neh2 domain (aa.1-86), which is the binding site for Keap1. Mutations in this region disrupt Keap1 binding, leading to Nrf2 nuclear translocation and increased mTOR signaling through RagD (Shibata Cancer Res 2010). We report translational studies and results from an ongoing phase 2 trial of the oral TORC1/2 inhibitor TAK-228. Methods: Cytotoxicity, signaling, and xenograft experiments were performed using LK-2 SQCLC cells (NFE2L2 E79K mut) treated with TAK-228, everolimus, rapamycin, or deforolimus. Pts with stage IV SQCLC harboring NFE2L2 or KEAP1 mutations and NSCLC harboring KRAS + NFE2L2 or KEAP1 co-mutations are treated on an NCI CTEP phase 2 study of TAK228 3mg po qd (continuous 28 day cycles; NCT02417701). Primary endpoint: ORR. Secondary endpoints: PFS. The study utilizes a Simon 2-stage design for each cohort with H0 = 5% (N≥1/5 responses), HA = 40% (N≥2/10 responses). Results: TAK-228 exhibited increased anti-tumor activity over TORC1 rapalogs in LK-2 cells. TAK-228 alone was cytotoxic at sub-[μM] (IC50 68nM); all other rapalogs exhibited IC50s > 10μM. This was associated with marked decrease in pS6, pAKT, and pERK. Tumor response (-55%) was seen in an LK-2 xenograft treated with TAK228. No anti-tumor/growth inhibitory response was seen with any other rapalog. N = 15 evaluable pts have been treated on study (7 NFE2L2, 3 KEAP1, 5 KRAS + NFE2L2 or KEAP1). 2 related-SAEs (G3 hyperglycemia, G3 confusion) were seen; there were no unexpected AEs. Within SQCLC NFE2L2 pts ORR = 29% (2/7 PR) and DCR = 100%. Prolonged duration of response is present, with PFS = 10.5mo, 11.4mo (18.2mo tx beyond PD), 6mo (8mo tx beyond PD), 5.5mo+, 4.5mo, and 1.5mo+. Within SQCLC KEAP1 pts DCR = 66% (2SD, 1PD) with PFS = 7.4mo+, 3mo+, 1mo. Data for the KRAS + NFE2L2/KEAP1 arm will be presented. Conclusions: TAK228 is tolerable with evidence of pre-clinical activity, radiographic responses, and prolonged DOR in biomarker-selected NSCLC pts. Accrual is ongoing. Clinical trial information: NCT02417701.
Determination of the ability of a novel, long-acting subcutaneous GnRH antagonist, VERU-100, to castrate without a testosterone surge in a rat model.
Authors: Getzenberg Robert H. , Lin Jui-Chen , Cerro Andrew , Rhodes Christopher A. , Steiner Mitchell S. 
Published: February 2020

128 Background: Androgen deprivation therapy (ADT) is the mainstay for the treatment of advanced prostate cancer. LHRH agonists are frequently used for ADT but these agents often result in initial surges in testosterone (T) levels. Although they do not result in initial T surges, current injectable GnRH antagonists are short term (1 month) subcutaneous (sc) depots that require a high volume loading dose followed by monthly maintenance dosing. VERU-100 is a novel GnRH decapeptide antagonist for long term suppression of T to castrate levels and is administered as a low volume sc injection without the requirement of a loading dose. Eight distinct formulations were evaluated in rats in order to select the best formulation, VERU-100. Methods: Male Sprague Dawley rats (n=3 per group) were injected sc through a 21G needle, with approximately 200 μl of each formulation at a dose level of 20 mg/kg. Eight groups consisting of the distinct test formulations were evaluated. Blood samples were drawn at weekly intervals until week 4 and then bi-weekly for pharmacokinetic (PK) (Integrated Analytical Solutions) and testosterone (T) level determinations (Cornell University Animal Health Diagnostic Center). Results: Within approximately 24 hours after administration of the GHRH antagonist formulations, testosterone levels in the rats went from a mean of 7.36 ng/ml to undetectable. The T levels resulting from a single injection of the lead formulation in these studies, VH-030-002, remained undetectable for greater than 26 weeks (6 months) as did the other formulations tested. The corresponding PK analysis demonstrated that the GnRH antagonist levels were detectable for greater than 26 weeks and remained above 1 ng/ml for almost all of the study points. The T levels correlated to the exposure from the formulations, and PKPD was as consistent for GnRH antagonists. Conclusions: VERU-100 is a novel GnRH antagonist formulation that in this rodent study, with a low injection volume, resulted in undetectable T for at least six months. No surge of T is observed after administration. An IND submission is anticipated in early 2020 for the dose finding Phase 2 trial in men with advanced prostate cancer.