bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using data to support evidence-informed decisions about skilled birth attendants in fragile contexts: a situational analysis from Democratic Republic of the Congo
Authors: Baba Amuda , Martineau Tim , Theobald Sally , Sabuni Paluku , Raven Joanna 
Published: October 2020

Abstract

Background
Most low- and middle-income countries are experiencing challenges in maternal health in relation to accessing skilled birth attendants (SBA). The first step in addressing this problem is understanding the current situation. We aimed to understand SBA’s availability and distribution in Ituri Province, North Eastern Democratic Republic of the Congo (DRC) from 2013 to 2017.

Methods
We used available data on SBAs (doctors, nurses and midwives) from the Ituri Provincial Human Resource for Health Management Unit’s database from 2013 to 2017. The current distribution across and within three categories of district (rural, peri-urban and urban) and characteristics of SBAs as well as 5-year trends and vacancy trends were identified. Data on training outputs for SBA cadres was collected from training schools in the province. Descriptive analysis, disaggregating by district, cadre and gender where possible, was conducted using Excel.

Results
The national ratio of SBAs per 1000 population is four times less than the Sustainable Development Goals threshold (4.45) while the Ituri Province ratio is one of the lowest in DRC. There are more doctors and nurses in urban and peri-urban districts compared to posts, and shortages of midwives in all district categories, particularly in rural districts. From 2013 to 2017, occupied posts for doctors and nurses in all three categories of districts increase while midwives decrease in peri-urban and rural districts. There is clear gender and occupational segregation: doctors and nurses are more likely to be male, whereas midwives are more likely to be female. The projections of training outputs show a surplus against authorised posts of doctors and nursing increasing, while the shortfall for midwives remains above 75%.

Conclusion
This is the first study to use existing human resource data to analyse availability and distribution of SBAs in a DRC province. This has provided insight into the mismatch of supply and demand of SBAs, highlighting the extreme shortage of midwives throughout the province. Further investigations are needed to better understand the situation and develop strategies to ensure a more equitable distribution of SBAs throughout this province and beyond. Without this, DRC will continue to struggle to reduce maternal mortality.
The formyl peptide receptor agonist Ac2-26 alleviates neuroinflammation in a mouse model of pneumococcal meningitis
Authors: Rüger Marvin , Kipp Eugenia , Schubert Nadine , Schröder Nicole , Pufe Thomas , Stope Matthias B. , Kipp Markus , Blume Christian , Tauber Simone C. , Brandenburg Lars-Ove 
Published: October 2020

Abstract

Background
Bacterial meningitis is still a cause of severe neurological disability. The brain is protected from penetrating pathogens by the blood-brain barrier and the innate immune system. The invading pathogens are recognized by pattern recognition receptors including the G-protein-coupled formyl peptide receptors (FPRs), which are expressed by immune cells of the central nervous system. FPRs show a broad spectrum of ligands, including pro- and anti-inflammatory ones. Here, we investigated the effects of the annexin A1 mimetic peptide Ac2-26 in a mouse model of pneumococcal meningitis.

Methods
Wildtype (WT) and Fpr1- and Fpr2-deficient mice were intrathecally infected with Streptococcus pneumoniae D39 (type 2). Subsequently, the different mice groups were treated by intraperitoneal injections of Ac2-26 (1 mg/kg body weight) 2, 8, and 24 h post-infection. The extent of inflammation was analyzed in various brain regions by means of immunohistochemistry and real-time reverse transcription polymerase chain reaction (RT-PCR) 30 h post-infection.

Results
Ac2-26-treated WT mice showed less severe neutrophil infiltration, paralleled by a reduced induction of pro-inflammatory glial cell responses in the hippocampal formation and cortex. While meningitis was ameliorated in Ac2-26-treated Fpr1-deficient mice, this protective effect was not observed in Fpr2-deficient mice. Irrespective of Ac2-26 treatment, inflammation was more severe in Fpr2-deficient compared to Fpr1-deficient mice.

Conclusions
In summary, this study demonstrates anti-inflammatory properties of Ac2-26 in a model of bacterial meningitis, which are mediated via FPR2, but not FPR1. Ac2-26 and other FPR2 modulators might be promising targets for the development of novel therapies for Streptococcus pneumoniae-induced meningitis.
Urban gardening and neglected and underutilized species in Salvador, Bahia, Brazil
Authors: da Cunha Manuela Alves , Paraguassú Lidice Almeida Arlego , Assis José Geraldo de Aquino , Silva Arthur Benjamin de Paula Carvalho , Cardoso Ryzia de Cassia Vieira 
Published: October 2020

Abstract

Background
Urban agriculture has been evidenced as a food production and environmental sustainability strategy, although it faces many obstacles in Latin American countries. Additionally, in urban areas, low consumption of fruit and greenery is noticeable, along with loss in food diversity, including the neglected and underutilized species (NUS), which involve potential to strengthen local food systems. For this reason, this work has sought to map urban gardens in the city of Salvador, Bahia, Brazil, characterizing their gardeners, and to systematize information regarding food produced and the use of NUS.

Methods
The municipality’s urban gardens were mapped and data was collected from the gardeners. The study included two steps: (i) garden localization; (ii) on-site visits for interviews with gardeners and verification of cultivated food, destination of production, availability, and use of NUS.

Results
Eighteen active food gardens were located, seventeen of which participated in the study: eight (8) communal (UCG) and nine (9) private (UPG). Respondents were on average 55.76 years old, mostly (52.9%) male, working at UPG (88.9%). Women predominated in the UCG (87.5%), with higher levels of education. For 52.9% of the interviewees, the garden was their main source of income. Food produced at the urban gardens was consumed by 82.4% of the gardeners and their families. In 70.6% of the gardens, production was also sold, while 47.1% donated. During the survey, 59 NUS were found and 76.5% of respondents reported consuming 19 of the species. NUS leaves, fruits, and seeds were found to be eaten raw, boiled, or sautéed in various preparations, especially Coleus amboinicus Lour. (76.5%), Eryngium foetidum L. (35.3%), Talinum fruticosum (L.) Juss., and Pereskia aculeata Mill (both 29.4%). Occurrence and utilization of NUS did not present significant associations with the gardens or gardeners (p > 0.05).

Conclusions
Salvador urban gardens, even in small numbers and without government support, have produced affordable food for the local population, preserved food diversity, and the tradition of NUS cultivation and use. Thus, urban gardens are reaffirmed as relevant spaces that should be included in public policies in order to promote food and nutritional security, biodiversity, and urban environmental sustainability.
Implementing a multilevel intervention to accelerate colorectal cancer screening and follow-up in federally qualified health centers using a stepped wedge design: a study protocol
Authors: Kim Karen , Polite Blasé , Hedeker Donald , Liebovitz David , Randal Fornessa , Jayaprakash Manasi , Quinn Michael , Lee Sang Mee , Lam Helen 
Published: October 2020

Abstract

Background
Screening for colorectal cancer (CRC) not only detects disease early when treatment is more effective but also prevents cancer by finding and removing precancerous polyps. Because many of our nation’s most disadvantaged and vulnerable individuals obtain health care at federally qualified health centers, these centers play a significant role in increasing CRC screening among the most vulnerable populations. Furthermore, the full benefits of cancer screenings must include timely and appropriate follow-up of abnormal results. Thus, the purpose of this study is to implement a multilevel intervention to increase rates of CRC screening, follow-up, and referral-to-care in federally qualified health centers, as well as simultaneously to observe and to gather information on the implementation process to improve the adoption, implementation, and sustainment of the intervention. The multilevel intervention will target three different levels of influences: organization, provider, and individual. It will have multiple components, including provider and staff education, provider reminder, provider assessment and feedback, patient reminder, and patient navigation.

Methods
This study is a multilevel, three-phase, stepped wedge cluster randomized trial with four clusters of clinics from four different FQHC systems. In the first phase, there will be a 3-month waiting period during which no intervention components will be implemented. After the 3-month waiting period, we will randomize two clusters to cross from the control to the intervention and the remaining two clusters to follow 3 months later. All clusters will stay at the same phase for 9 months, followed by a 3-month transition period, and then cross over to the next phase.

Discussion
There is a pressing need to reduce disparities in CRC outcomes, especially among racial/ethnic minority populations and among populations who live in poverty. Single-level interventions are often insufficient to lead to sustainable changes. Multilevel interventions, which target two or more levels of changes, are needed to address multilevel contextual influences simultaneously. Multilevel interventions with multiple components will affect not only the desired outcomes but also each other. How to take advantage of multilevel interventions and how to implement such interventions and evaluate their effectiveness are the ultimate goals of this study.

Trial registration
This protocol is registered at clinicaltrials.gov (NCT04514341) on 14 August 2020.
The clonogenic assay: robustness of plating efficiency-based analysis is strongly compromised by cellular cooperation
Authors: Brix Nikko , Samaga Daniel , Hennel Roman , Gehr Katharina , Zitzelsberger Horst , Lauber Kirsten 
Published: October 2020

Abstract
Background
The clonogenic assay is a versatile and frequently used tool to quantify reproductive cell survival in vitro. Current state-of-the-art analysis relies on plating efficiency-based calculations which assume a linear correlation between the number of cells seeded and the number of colonies counted. The present study was designed to test the validity of this assumption and to evaluate the robustness of clonogenic survival results obtained.

Methods
A panel of 50 established cancer cell lines was used for comprehensive evaluation of the clonogenic assay procedure and data analysis. We assessed the performance of plating efficiency-based calculations and examined the influence of critical experimental parameters, such as cell density seeded, assay volume, incubation time, as well as the cell line-intrinsic factor of cellular cooperation by auto-/paracrine stimulation. Our findings were integrated into a novel mathematical approach for the analysis of clonogenic survival data.

Results
For various cell lines, clonogenic growth behavior failed to be adequately described by a constant plating efficiency, since the density of cells seeded severely influenced the extent and the dynamics of clonogenic growth. This strongly impaired the robustness of survival calculations obtained by the current state-of-the-art method using plating efficiency-based normalization. A novel mathematical approach utilizing power regression and interpolation of matched colony numbers at different irradiation doses applied to the same dataset substantially reduced the impact of cell density on survival results. Cellular cooperation was observed to be responsible for the non-linear clonogenic growth behavior of a relevant number of cell lines and the impairment of survival calculations. With 28/50 cell lines of different tumor entities showing moderate to high degrees of cellular cooperation, this phenomenon was found to be unexpectedly common.

Conclusions
Our study reveals that plating efficiency-based analysis of clonogenic survival data is profoundly compromised by cellular cooperation resulting in strongly underestimated assay-intrinsic errors in a relevant proportion of established cancer cell lines. This severely questions the use of plating efficiency-based calculations in studies aiming to achieve more than semiquantitative results. The novel approach presented here accounts for the phenomenon of cellular cooperation and allows the extraction of clonogenic survival results with clearly improved robustness.
Long noncoding RNA UPK1A-AS1 indicates poor prognosis of hepatocellular carcinoma and promotes cell proliferation through interaction with EZH2
Authors: Zhang Dong-Yan , Sun Qing-Can , Zou Xue-Jing , Song Yang , Li Wen-Wen , Guo Ze-Qin , Liu Shan-Shan , Liu Li , Wu De-Hua 
Published: October 2020

Abstract

Background
Dysregulation of long non-coding RNAs (lncRNAs) is responsible for cancer initiation and development, positioning lncRNAs as not only biomarkers but also promising therapeutic targets for cancer treatment. A growing number of lncRNAs have been reported in hepatocellular carcinoma (HCC), but their functional and mechanistic roles remain unclear.

Methods
Gene Set Enrichment Analysis was used to investigate the molecular mechanism of UPK1A antisense RNA 1 (UPK1A-AS1). Cell Counting Kit-8 assays, EdU assays, flow cytometry, western blotting, and xenograft assays were used to confirm the role of UPK1A-AS1 in the proliferation of HCC cells in vitro and in vivo. Bioinformatics analyses and quantitative polymerase chain reaction (qRT-PCR) were performed to explore the interplay between UPK1A-AS1 and enhancer of zeste homologue 2 (EZH2). RNA immunoprecipitation (RIP), RNA pull-down assays, western blotting, and qRT-PCR were conducted to confirm the interaction between UPK1A-AS1 and EZH2. The interaction between UPK1A-AS1 and miR-138-5p was examined by luciferase reporter and RIP assays. Finally, the expression level and prognosis value of UPK1A-AS1 in HCC were analyzed using RNA sequencing data from The Cancer Genome Atlas datasets.

Results
We showed that UPK1A-AS1, a newly identified lncRNA, promoted cellular proliferation and tumor growth by accelerating cell cycle progression. Cell cycle-related genes, including CCND1, CDK2, CDK4, CCNB1, and CCNB2, were significantly upregulated in HCC cells overexpressing UPK1A-AS1. Furthermore, overexpression of UPK1A-AS1 could protect HCC cells from cis-platinum toxicity. Mechanistically, UPK1A-AS1 interacted with EZH2 to mediate its nuclear translocation and reinforce its binding to SUZ12, leading to increased H27K3 trimethylation. Targeting EZH2 with specific small interfering RNA impaired the UPK1A-AS1-mediated upregulation of proliferation and cell cycle progression-related genes. Moreover, miR-138-5p was identified as a direct target of UPK1A-AS1. Additionally, UPK1A-AS1 was significantly upregulated in HCC, and the upregulation of UPK1A-AS1 predicted poor prognosis for patients with HCC.

Conclusions
Our study revealed that UPK1A-AS1 promotes HCC development by accelerating cell cycle progression through interaction with EZH2 and sponging of miR-138-5p, suggesting that UPK1A-AS1 possesses substantial potential as a novel biomarker for HCC prognosis and therapy.
Practicing outcome-based medical care using pragmatic care trials
Authors: Darsaut Tim E. , Raymond Jean 
Published: October 2020

Abstract
The current separation between medical research and care is an obstacle to essential aspects of good medical practice: the verification that care interventions actually deliver the good outcomes they promise, and the use of scientific methods to optimize care under uncertainty. Pragmatic care trials have been designed to address these problems. Care trials are all-inclusive randomized trials integrated into care. Every item of trial design is selected in the best medical interest of participating patients. Care trials can eventually show what constitutes good medical practice based on patient outcomes. In the meantime, care trials give clinicians and patients the scientific methods necessary for optimization of medical care when no one really knows what to do.
We report the progress of 9 randomized care trials that were used to guide the endovascular or surgical management of 1212 patients with acute stroke, intracranial aneurysms, and arteriovenous malformations in a single center in an elective or acute care context. Care trials were used to address long-standing dilemmas regarding rival medical, surgical, or endovascular management options or to offer innovative instead of standard treatments. The trial methodology, by replacing unrepeatable treatment decisions by 1:1 randomized allocation whenever reliable knowledge was not available, had an immediate impact, transforming unverifiable dogmatic medical practice into verifiable outcome-based medical care. We believe the approach is applicable to all medical or surgical domains, but widespread adoption may require the revision of many currently prevalent views regarding the role of research in clinical practice.
Challenges and opportunities for improving the landscape for Lewy body dementia clinical trials
Authors: Goldman Jennifer G. , Forsberg Leah K. , Boeve Bradley F. , Armstrong Melissa J. , Irwin David J. , Ferman Tanis J. , Galasko Doug , Galvin James E. , Kaufer Daniel , Leverenz James , Lippa Carol F. , Marder Karen , Abler Victor , Biglan Kevin , Irizarry Michael , Keller Bill , Munsie Leanne , Nakagawa Masaki , Taylor Angela , Graham Todd 
Published: October 2020

AbstractLewy body dementia (LBD), including dementia with Lewy bodies and Parkinson’s disease dementia, affects over a million people in the USA and has a substantial impact on patients, caregivers, and society. Symptomatic treatments for LBD, which can include cognitive, neuropsychiatric, autonomic, sleep, and motor features, are limited with only two drugs (cholinesterase inhibitors) currently approved by regulatory agencies for dementia in LBD. Clinical trials represent a top research priority, but there are many challenges in the development and implementation of trials in LBD. To address these issues and advance the field of clinical trials in the LBDs, the Lewy Body Dementia Association formed an Industry Advisory Council (LBDA IAC), in addition to its Research Center of Excellence program. The LBDA IAC comprises a diverse and collaborative group of experts from academic medical centers, pharmaceutical industries, and the patient advocacy foundation. The inaugural LBDA IAC meeting, held in June 2019, aimed to bring together this group, along with representatives from regulatory agencies, to address the topic of optimizing the landscape of LBD clinical trials. This review highlights the formation of the LBDA IAC, current state of LBD clinical trials, and challenges and opportunities in the field regarding trial design, study populations, diagnostic criteria, and biomarker utilization. Current gaps include a lack of standardized clinical assessment tools and evidence-based management strategies for LBD as well as difficulty and controversy in diagnosing LBD. Challenges in LBD clinical trials include the heterogeneity of LBD pathology and symptomatology, limited understanding of the trajectory of LBD cognitive and core features, absence of LBD-specific outcome measures, and lack of established standardized biologic, imaging, or genetic biomarkers that may inform study design. Demands of study participation (e.g., travel, duration, and frequency of study visits) may also pose challenges and impact trial enrollment, retention, and outcomes. There are opportunities to improve the landscape of LBD clinical trials by harmonizing clinical assessments and biomarkers across cohorts and research studies, developing and validating outcome measures in LBD, engaging the patient community to assess research needs and priorities, and incorporating biomarker and genotype profiling in study design.
Degos disease: a case report and review of the literature
Authors: Tummidi Santosh , Nagendran Prabhakaran , Gedela Swaroopa , Ramani Jami Rupa , Shankaralingappa Arundhathi 
Published: October 2020

Abstract

Background
Degos disease is a very rare syndrome with multisystem vasculopathy of unknown cause. It can affect the skin, gastrointestinal tract, and central nervous system. However, other organs such as the kidney, lungs, pleura, and liver can also be involved.

Case presentation
A 35-year-old Hindu woman presented to our dermatology outpatient department with complaints of depigmented painful lesions. A skin punch biopsy taken from the porcelain white atrophic papules which revealed features of Degos disease.

Conclusion
The diagnosis of Degos disease is usually based on the presence of the pathognomonic skin lesions and a tissue biopsy demonstrating a wedge-shaped area of necrosis with thrombotic occlusion of the small arterioles. No specific treatment is currently available for this disease.
Detection of CMY-type beta-lactamases in Escherichia coli isolates from paediatric patients in a tertiary care hospital in Mexico
Authors: Merida-Vieyra Jocelin , De Colsa-Ranero Agustín , Calderón-Castañeda Yair , Aquino-Andrade Alejandra 
Published: October 2020

Abstract

Background
The aim of this study was to detect CMY-type beta-lactamases in E. coli isolates obtained from paediatric patients.

Methods
In total, 404 infection-causing E. coli isolates resistant to third and fourth generation cephalosporins (3GC, 4GC) were collected from paediatric patients over a 2 years period. The identification and susceptibility profiles were determined with an automated microbiology system. Typing of blaCMY and other beta-lactamase genes (blaTEM, blaSHV, blaCTX-M, blaVIM, blaIMP, blaKPC, blaNDM, blaOXA and blaGES) was realized by PCR and sequencing. Phenotypic detection of AmpC-type enzymes was performed using boronic acid (20 mg/mL) and cloxacillin (20 mg/mL) as inhibitors, and the production of extended-spectrum beta-lactamases was determined with the double-disk diffusion test with cefotaxime (CTX) and ceftazidime (CAZ) discs alone and in combination with clavulanic acid. The CarbaNP test and modified carbapenem inhibition method (mCIM) were used for isolates with decreased susceptibility to carbapenems. The clonal origin of the isolates was established by pulsed-field gel electrophoresis (PFGE), phylotyping method and multilocus sequence typing.

Results
CMY-type beta-lactamases were detected in 18 isolates (4.5%). The allelic variants found were CMY-2 (n = 14) and CMY-42 (n = 4). Of the E. coli strains with CMY, the AmpC phenotypic production test was positive in 11 isolates with cloxacillin and in 15 with boronic acid. ESBL production was detected in 13 isolates. Coexistence with other beta-lactamases was observed such as CTX-M-15 ESBL and original spectrum beta-lactamases TEM-1 and TEM-190. In one isolate, the CarbaNP test was negative, the mCIM was positive, and OXA-48 carbapenemase was detected. Phylogroup A was the most frequent (n = 9) followed by B2, E and F (n = 2, respectively), and through PFGE, no clonal relationship was observed. Eleven different sequence types (ST) were found, with ST10 high-risk clone being the most frequent (n = 4). Seventy-two percent of the isolates were from health care-associated infections; the mortality rate was 11.1%.

Conclusions
This is the first report in Mexico of E. coli producing CMY isolated from paediatric patients, demonstrating a frequency of 4.5%. In addition, this is the first finding of E. coli ST10 with CMY-2 and OXA-48.