bluuebunny/crossref_metadata_2025_split huggingface dataset:
Health workforce demography: a framework to improve understanding of the health workforce and support achievement of the Sustainable Development Goals
Authors: Szabo Sylvia , Nove Andrea , Matthews Zoë , Bajracharya Ashish , Dhillon Ibadat , Singh Devendra Raj , Saares Aurora , Campbell James 
Published: January 2020

AbstractThe ambition of universal health coverage entails estimation of the number, type and distribution of health workers required to meet the population need for health services. The demography of the population, including anticipated or estimated changes, is a factor in determining the ‘universal’ needs for health and well-being. Demography is concerned with the size, breakdown, age and gender structure and dynamics of a population. The same science, and its robust methodologies, is equally applicable to the demography of the health workforce itself. For example, a large percentage of the workforce close to retirement will impact availability, a geographically mobile workforce has implications for health coverage, and gender distribution in occupations may have implications for workforce acceptability and equity of opportunity. In a world with an overall shortage of health workers, and the expectation of increasing need as a result of both population growth in the global south and population ageing in the global north, studying and understanding demographic characteristics of the workforce can help with future planning. This paper discusses the dimensions of health worker demography and considers how demographic tools and techniques can be applied to the analysis of the health labour market. A conceptual framework is introduced as a step towards the application of demographic principles and techniques to health workforce analysis and planning exercises as countries work towards universal health coverage, the reduction of inequities and national development targets. Some illustrative data from Nepal and Finland are shown to illustrate the potential of this framework as a simple and effective contribution to health workforce planning.
Lycopene and bone: an in vitro investigation and a pilot prospective clinical study
Authors: Russo Cristina , Ferro Yvelise , Maurotti Samantha , Salvati Maria Antonietta , Mazza Elisa , Pujia Roberta , Terracciano Rosa , Maggisano Giuseppina , Mare Rosario , Giannini Sandro , Romeo Stefano , Pujia Arturo , Montalcini Tiziana 
Published: January 2020

AbstractBackgroundThere are several effective therapies for osteoporosis but these agents might cause serious adverse events. Lycopene intake could prevent bone loss, however studies on its effects on bone are scarce. Our aim was to investigate the effects of lycopene on osteoblast cells as well as bone mineral density and bone turnover markers in postmenopausal women.MethodsWe investigated the effect of lycopene on the Wnt/β-catenin and ERK 1/2 pathways, RUNX2, alkaline phosphatase, RANKL and COL1A of Saos-2. We also carried out a pilot controlled clinical study to verify the feasibility of an approach for bone loss prevention through the intake of a lycopene-rich tomato sauce in 39 postmenopausal women.ResultsLycopene 10 µM resulted in higher β-catenin and phERK1/2 proteinVsthe vehicle (p = 0.04 and p = 0.006). RUNX2 and COL1A mRNA was induced by both 5 and 10 µM doses (p = 0.03; p = 0.03 and p = 0.03; p = 0.05) while RANKL mRNA was reduced (p < 0.05). A significant bone density loss was not detected in women taking the tomato sauce while the control group had bone loss (p = 0.002). Tomato sauce intake resulted in a greater bone alkaline phosphatase reduction than the control (18% vs 8.5%, p = 0.03).ConclusionsLycopene activates the WNT/β-catenin and ERK1/2 pathways, upregulates RUNX2, alkaline phosphatase, COL1A and downregulates RANKL Saos-2. These processes contributed to prevent bone loss in postmenopausal women.
Effects of PM2.5 and gases exposure during prenatal and early-life on autism–like phenotypes in male rat offspring
Authors: Emam Baharan , Shahsavani Abbas , Khodagholi Fariba , Zarandi Saeed Motesaddi , Hopke Philip K. , Hadei Mostafa , Behbahani Hamidreza , Yarahmadi Maryam 
Published: January 2020

Abstract
Background
Epidemiological studies have reported associations between elevated air pollution and autism spectrum disorders (ASD). However, we hypothesized that exposure to air pollution that mimics real world scenarios, is a potential contributor to ASD. The exact etiology and molecular mechanisms underlying ASD are not well understood. Thus, we assessed whether changes in OXTR levels may be part of the mechanism linking PM2.5/gaseous pollutant exposure and ASD. The current in-vivo study investigated the effect of exposure to fine particulate matter (PM2.5) and gaseous pollutants on ASD using behavioral and molecular experiments. Four exposure groups of Wistar rats were included in this study: 1) particulate matter and gaseous pollutants exposed (PGE), 2) gaseous pollutants only exposed (GE), 3) autism-like model (ALM) with VPA induction, and 4) clean air exposed (CAE) as the control. Pregnant dams and male pups were exposed to air pollutants from embryonic day (E0) to postnatal day (PND21).

Results
The average ± SD concentrations of air pollutants were: PM2.5: 43.8 ± 21.1 μg/m3, CO: 13.5 ± 2.5 ppm, NO2: 0.341 ± 0.100 ppm, SO2: 0.275 ± 0.07 ppm, and O3: 0.135 ± 0.01 ppm. The OXTR protein level, catalase activity (CAT), and GSH concentrations in the ALM, PGE, and GE rats were lower than those in control group (CAE). However, the decrements in the GE rats were smaller than other groups. Also in behavioral assessments, the ALM, PGE, and GE rats demonstrated a repetitive /restricted behavior and poor social interaction, but the GE rats had weaker responses compared to other groups of rats. The PGE and GE rats showed similar trends in these tests compared to the VPA rats.

Conclusions
This study suggested that exposure to ambient air pollution contributed to ASD and that OXTR protein may serve as part of the mechanism linking them.
The protective effects of PI3K/Akt pathway on human nucleus pulposus mesenchymal stem cells against hypoxia and nutrition deficiency
Authors: Tian DaSheng , Liu Jianjun , Chen Lei , Zhu Bin , Jing Juehua 
Published: January 2020

Abstract
Background
To study the effects of hypoxia and nutrition deficiency mimicking degenerated intervertebral disc on the biological behavior of human nucleus-derived pulposus mesenchymal stem cells (hNP-MSCs) and the role of PI3K/Akt pathway in the process in vitro.

Methods
hP-MSCs were isolated from lumbar disc and were further identified by their immunophenotypes and multilineage differentiation. Then, cells were divided into the control group, hypoxia and nutrition deficiency group, the LY294002 group, and insulin-like growth factor 1 (IGF-1) group. Then cell apoptosis, the cell viability, the caspase 3 activity, and the expression of PI3K, Akt, and functional genes (aggrecan, collagen I, and collagen II) were evaluated.

Result
Our work showed that isolated cells met the criteria of International Society for cellular Therapy. Therefore, cells obtained from degenerated nucleus pulposus were definitely hNP-MSCs. Our results showed that hypoxia and nutrition deficiency could significantly increase cell apoptosis, the caspase 3 activity, and inhibit cell viability. Gene expression results demonstrated that hypoxia and nutrition deficiency could increase the relative expression of PI3K and Akt gene and inhibit the expression of functional genes. However, when the PI3K/Akt pathway was inhibited by LY294002, the cell apoptosis and caspase 3 activity significantly increased while the cell viability was obviously inhibited. Quantitative real-time PCR results showed that the expression of functional genes was more significantly inhibited. Our study further verified that the above-mentioned biological activities of hNP-MSCs could be significantly improved by IGF1.

Conclusions
PI3K/Akt signal pathway may have protective effects on human nucleus pulposus-derived mesenchymal stem cells against hypoxia and nutrition deficiency.
Paradigm shift in the diagnosis of peste des petits ruminants: scoping review
Authors: Kinimi Edson , Odongo Steven , Muyldermans Serge , Kock Richard , Misinzo Gerald 
Published: January 2020

AbstractPeste des petits ruminants viruscauses a highly contagious disease, which poses enormous economic losses in domestic animals and threatens the conservation of wild herbivores. Diagnosis remains a cornerstone to the Peste des petits ruminants Global Control and Eradication Strategy, an initiative of the World Organisation for Animal Health and the Food and Agriculture Organisation. The present review presents the peste des petits ruminants diagnostic landscape, including the practicality of commercially available diagnostic tools, prototype tests and opportunities for new technologies. The most common peste des petits ruminants diagnostic tools include; agar gel immunodiffusion, counter-immunoelectrophoresis, enzyme-linked immunosorbent assays, reverse transcription polymerase chain reaction either gel-based or real-time, reverse transcription loop-mediated isothermal amplification, reverse transcription recombinase polymerase amplification assays, immunochromatographic lateral flow devices, luciferase immunoprecipitation system and pseudotype-based assays. These tests vary in their technical demands, but all require a laboratory with exception of immunochromatographic lateral flow and possibly reverse transcription loop-mediated isothermal amplification and reverse transcription recombinase polymerase amplification assays. Thus, we are proposing an efficient integration of diagnostic tests for rapid and correct identification of peste des petits ruminants in endemic zones and to rapidly confirm outbreaks. Deployment of pen-side tests will improve diagnostic capacity in extremely remote settings and susceptible wildlife ecosystems, where transportation of clinical samples in the optimum cold chain is unreliable.
Chromoanagenesis: a piece of the macroevolution scenario
Authors: Pellestor Franck , Gatinois Vincent 
Published: January 2020

AbstractOver the last decade, new types of massive and complex chromosomal rearrangements based on the chaotic shattering and restructuring of chromosomes have been identified in cancer cells as well as in patients with congenital diseases and healthy individuals. These unanticipated phenomena are named chromothripsis, chromoanasynthesis and chromoplexy, and are grouped under the term of chromoanagenesis. As mechanisms for rapid and profound genome modifications in germlines and early development, these processes can be regarded as credible pathways for genomic evolution and speciation process. Their discovery confirms the importance of genome-centric investigations to fully understand organismal evolution.Because they oppose the model of progressive acquisition of driver mutations or rearrangements, these phenomena conceptually give support to the concept of macroevolution, known through the models of “Hopeful Monsters” and the “Punctuated Equilibrium”. In this review, we summarize mechanisms underlying chromoanagenesis processes and we show that numerous cases of chromosomal speciation and short-term adaptation could be correlated to chromoanagenesis-related mechanisms.In the frame of a modern and integrative analysis of eukaryote evolutionary processes, it seems important to consider the unexpected chromoanagenesis phenomena.
TRPC1 mediates slow excitatory synaptic transmission in hippocampal oriens/alveus interneurons
Authors: Kougioumoutzakis André , Pelletier Joe Guillaume , Laplante Isabel , Khlaifia Abdessattar , Lacaille Jean-Claude 
Published: January 2020

AbstractHippocampal GABAergic interneurons play key roles in regulating principal cell activity and plasticity. Interneurons located in stratum oriens/alveus (O/A INs) receive excitatory inputs from CA1 pyramidal cells and express a Hebbian form of long-term potentiation (LTP) at their excitatory input synapses. This LTP requires the activation of metabotropic glutamate receptors 1a (mGluR1a) and Ca2+ entry via transient receptor potential (TRP) channels. However, the type of TRP channels involved in synaptic transmission at these synapses remains largely unknown. Using patch-clamp recordings, we show that slow excitatory postsynaptic currents (EPSCs) evoked in O/A INs are dependent on TRP channels but may be independent of phospholipase C. Using reverse transcription polymerase chain reaction (RT-PCR) we found that mRNA for TRPC 1, 3–7 was present in CA1 hippocampus. Using single-cell RT-PCR, we found expression of mRNA for TRPC 1, 4–7, but not TRPC3, in O/A INs. Using co-immunoprecipitation assays in HEK-293 cell expression system, we found that TRPC1 and TRPC4 interacted with mGluR1a. Co-immunoprecipitation in hippocampus showed that TRPC1 interacted with mGluR1a. Using immunofluorescence, we found that TRPC1 co-localized with mGluR1a in O/A IN dendrites, whereas TRPC4 localization appeared limited to O/A IN cell body. Down-regulation of TRPC1, but not TRPC4, expression in O/A INs using small interfering RNAs prevented slow EPSCs, suggesting that TRPC1 is an obligatory TRPC subunit for these EPSCs. Our findings uncover a functional role of TRPC1 in mGluR1a-mediated slow excitatory synaptic transmission onto O/A INs that could be involved in Hebbian LTP at these synapses.
Determinants of preterm birth among mothers who gave birth in East Africa: systematic review and meta-analysis
Authors: Laelago Tariku , Yohannes Tadele , Tsige Gulima 
Published: January 2020

Abstract
Background
Preterm birth (PTB) can be caused by different factors. The factors can be classified into different categories: socio demographic, obstetric, reproductive health, medical, behavioral and nutritional related. The objective of this review was identifying determinants of PTB among mothers who gave birth in East African countries.

Methods
We have searched the following electronic bibliographic databases: PubMed, Google scholar, Cochrane library, AJOL (African journal online). Cross sectional, case control and cohort study published in English were included. There was no restriction on publication period. Studies with no abstracts and or full texts, editorials, and qualitative in design were excluded. Funnel plot was used to check publication bias. I-squared statistic was used to check heterogeneity. Pooled analysis was done by using fixed and random effect model. The Joanna Briggs Critical Appraisal Tools for review and meta-analysis was used to check the study quality.

Results
A total of 58 studies with 134,801 participants were used to identify determinants of PTB. On pooled analysis, PTB was associated with age < 20 years (AOR 1.76, 95% CI: 1.33–2.32), birth interval less than 24 months (AOR 2.03, 95% CI 1.57–2.62), multiple pregnancy (AOR 3.44,95% CI: 3.02–3.91), < 4 antenatal care (ANC) visits (AOR 5.52, 95% CI: 4.32–7.05), and absence of ANC (AOR 5.77, 95% CI: 4.27–7.79). Other determinants of PTB included: Antepartum hemorrhage (APH) (AOR 4.90, 95% CI: 3.48–6.89), pregnancy induced hypertension (PIH) (AOR 3.10, 95% CI: 2.34–4.09), premature rupture of membrane (PROM) (AOR 5.90, 95% CI: 4.39–7.93), history of PTB (AOR 3.45, 95% CI: 2.72–4.38), and history of still birth/abortion (AOR 3.93, 95% CI: 2.70–5.70). Furthermore, Anemia (AOR 4.58, 95% CI: 2.63–7.96), HIV infection (AOR 2.59, 95% CI: 1.84–3.66), urinary tract infection (UTI) (AOR 5.27, 95% CI: 2.98–9.31), presence of vaginal discharge (AOR 5.33, 95% CI: 3.19–8.92), and malaria (AOR 3.08, 95% CI: 2.32–4.10) were significantly associated with PTB.

Conclusions
There are many determinants of PTB in East Africa. This review could provide policy makers, clinicians, and program officers to design intervention on preventing occurrence of PTB.
Effects of endovascular and surface cooling on resuscitation in patients with cardiac arrest and a comparison of effectiveness, stability, and safety: a systematic review and meta-analysis
Authors: Liao Xueli , Zhou Ziyu , Zhou Manhong , Tang Hui , Feng Menglong , Kou Bujin , Zhu Ni , Liao Futuan , Wu Liaozhang 
Published: January 2020

AbstractObjectivesThis study conducted a meta-analysis to assess the effectiveness, stability, and safety of mild therapeutic hypothermia (TH) induced by endovascular cooling (EC) and surface cooling (SC) and its effect on ICU, survival rate, and neurological function integrity in adult CA patients.MethodsWe developed inclusion criteria, intervention protocols, results, and data collection. The results included outcomes during target temperature management as well as ICU stay, survival rate, and neurological functional integrity. The characteristics of the included population and each study were analyzed.ResultsFour thousand nine hundred thirteen participants met the inclusion criteria. Those receiving EC had a better cooling efficiency (cooling rates MD = 0.31[0.13, 0.50],p < 0.01; induced cooling times MD = − 90.45[− 167.57, − 13.33],p = 0.02; patients achieving the target temperature RR = 1.60[1.19, 2.15],p < 0.01) and thermal stability during the maintenance phase (maintenance time MD = 2.35[1.22, 3.48],p < 0.01; temperature fluctuation MD = − 0.68[− 1.03, − 0.33],p < 0.01; overcooling RR = 0.33[0.23, 0.49],p < 0.01). There were no differences in ICU survival rate (RR = 1.22[0.98, 1.52],p = 0.07,I2 = 0%) and hospital survival rate (RR = 1.02 [0.96, 1.09],p = 0.46,I2 = 0%), but EC reduced the length of stay in ICU (MD = − 1.83[− 3.45, − 0.21],p = 0.03,I2 = 49%) and improved outcome of favorable neurological function at discharge (RR = 1.15[1.04, 1.28],p < 0.01,I2 = 0%). EC may delay the hypothermia initiation time, and there was no significant difference between the two cooling methods in the time from the start of patients’ cardiac arrest to achieve the target temperature (MD = − 46.64[− 175.86, 82.58]). EC was superior to non-ArcticSun in terms of cooling efficiency. Although there was no statistical difference in ICU survival rate, ICU length of stay, and hospitalization survival rate, in comparison to non-ArcticSun, EC improved rates of neurologically intact survival (RR = 1.16 [1.01, 1.35],p = 0.04,I2 = 0%).ConclusionsAmong adult patients receiving cardiopulmonary resuscitation, although there is no significant difference between the two cooling methods in the time from the start of cardiac arrest to achieve the target temperature, the faster cooling rate and more stable cooling process in EC shorten patients’ ICU hospitalization time and help more patients obtain good neurological prognosis compared with patients receiving SC. Meanwhile, although EC has no significant difference in patient outcomes compared with ArcticSun, EC has improved rates of neurologically intact survival.
A deep learning image-based intrinsic molecular subtype classifier of breast tumors reveals tumor heterogeneity that may affect survival
Authors: Jaber Mustafa I. , Song Bing , Taylor Clive , Vaske Charles J. , Benz Stephen C. , Rabizadeh Shahrooz , Soon-Shiong Patrick , Szeto Christopher W. 
Published: January 2020

Abstract
Background
Breast cancer intrinsic molecular subtype (IMS) as classified by the expression-based PAM50 assay is considered a strong prognostic feature, even when controlled for by standard clinicopathological features such as age, grade, and nodal status, yet the molecular testing required to elucidate these subtypes is not routinely performed. Furthermore, when such bulk assays as RNA sequencing are performed, intratumoral heterogeneity that may affect prognosis and therapeutic decision-making can be missed.

Methods
As a more facile and readily available method for determining IMS in breast cancer, we developed a deep learning approach for approximating PAM50 intrinsic subtyping using only whole-slide images of H&E-stained breast biopsy tissue sections. This algorithm was trained on images from 443 tumors that had previously undergone PAM50 subtyping to classify small patches of the images into four major molecular subtypes—Basal-like, HER2-enriched, Luminal A, and Luminal B—as well as Basal vs. non-Basal. The algorithm was subsequently used for subtype classification of a held-out set of 222 tumors.

Results
This deep learning image-based classifier correctly subtyped the majority of samples in the held-out set of tumors. However, in many cases, significant heterogeneity was observed in assigned subtypes across patches from within a single whole-slide image. We performed further analysis of heterogeneity, focusing on contrasting Luminal A and Basal-like subtypes because classifications from our deep learning algorithm—similar to PAM50—are associated with significant differences in survival between these two subtypes. Patients with tumors classified as heterogeneous were found to have survival intermediate between Luminal A and Basal patients, as well as more varied levels of hormone receptor expression patterns.

Conclusions
Here, we present a method for minimizing manual work required to identify cancer-rich patches among all multiscale patches in H&E-stained WSIs that can be generalized to any indication. These results suggest that advanced deep machine learning methods that use only routinely collected whole-slide images can approximate RNA-seq-based molecular tests such as PAM50 and, importantly, may increase detection of heterogeneous tumors that may require more detailed subtype analysis.
Hc-hrg-2, a glutathione transferase gene, regulates heme homeostasis in the blood-feeding parasitic nematode Haemonchus contortus
Authors: Zhou Jing-Ru , Bu Dan-Ru , Zhao Xian-Feng , Wu Fei , Chen Xue-Qiu , Shi Heng-Zhi , Yao Chao-Qun , Du Ai-Fang , Yang Yi 
Published: January 2020

Abstract
Background
Haemonchus contortus, a blood-feeding parasite, is constantly surrounded by large quantities of heme released from the catabolism of host red blood cells. To cope with the toxicity of free heme, H. contortus needs to uptake and detoxify the heme, a process believed to be paramount for parasite survival.

Methods
A heme-responsive gene Hc-hrg-2 was identified which is the homologue of Ce-hrg-2. The transcriptional levels in all developmental stages and heme-responsive ability of Hc-hrg-2 were analyzed by qRT-PCR. Immunofluorescence analysis and cell transfections were performed to analyze the expression pattern of Hc-HGR-2. Statistical analyses were performed with GraghPad Prism 6.0 using Student’s t-test.

Results
To investigate the heme homeostasis of H. contortus, we first identified a heme-responsive gene Hc-hrg-2, a homolog of Ce-hrg-2 that is involved in heme transport in the hypodermis of Caenorhabditis elegans. Using qRT-PCR, we showed that Hc-hrg-2 mRNA was expressed throughout all life-cycle stages of H. contortus with the highest level in the third-stage larvae (L3s). Notably, transcription of Hc-hrg-2 in the exsheathed L3s was significantly upregulated in the presence of high concentration of heme. We found that Hc-HRG-2 protein was mainly located in the hypodermal tissues of adult H. contortus in vivo and the endoplasmic reticulum in the transfected mammalian cells. Our in vitro assay demonstrated that Hc-HRG-2 is a heme-binding protein with glutathione S-transferase activity and heme had a significant effect on its enzymatic activity when a model substrate 1-chloro-2, 4-dinitrobenzene (CDNB) was used.

Conclusions
Hc-hrg-2 is a heme-responsive gene and engaged in heme homeostasis regulation in hypodermal tissues during the free-living stages of H. contortus.