bluuebunny/crossref_metadata_2025_split huggingface dataset:
Toward Understanding the Occurrence of Both Wet and Dry Sahel Seasons during El Niño: The Modulating Role of the Global Ocean
Authors: Pomposi Catherine , Kushnir Yochanan , Giannini Alessandra , Biasutti Michela 
Published: November 2019

AbstractPrior research has shown that dry conditions tend to persist in the Sahel when El Niño develops. Yet, during the historic 2015 El Niño, Sahel summer precipitation was anomalously high, particularly in the second half of the season. This seeming inconsistency motivates a reexamination of the variability of precipitation during recent El Niño years. We identify and composite around two different outcomes for Sahel summer season: an anomalously wet season or an anomalously dry season as El Niño develops to its peak conditions over the observational record spanning 1950–2015. We find consistently cool temperatures across the global tropics outside the Niño-3.4 region when the Sahel is anomalously wet during El Niño years and a lack of cooling throughout the tropics when the Sahel is anomalously dry. The striking differences in oceanic surface temperatures between wet years and dry years are consistent with a rearrangement of the entire global circulation in favor of increased rainfall in West Africa despite the presence of El Niño.
The long-term survival of patients with III-IVb stage nasopharyngeal carcinoma treated with IMRT with or without Nimotuzumab: a propensity score-matched analysis
Authors: Zhi-Qiang Wang , Qi Mei , Ji-Bin Li , Rui You , You-Ping Liu , Rui Sun , Guang-Yuan Hu , Ming-Yuan Chen , Yi-Jun Hua 
Published: November 2019

AbstractBackgroundTo assess the efficacy of Nimotuzumab in combination with first-line chemoradiotherapy treatment in Chinese patients with primary III-IVb stage nasopharyngeal carcinoma.MethodsPatients with primary locoregionally advanced nasopharyngeal carcinoma who were treated with intensity-modulated radiotherapy (IMRT) and concurrent cisplatin-based chemotherapy between January 2008 and December 2013 at a single institution were retrospectively reviewed. Group A received at least 6 doses of Nimotuzumab, while Group B did not receive Nimotuzumab. A propensity score matching method was used to match patients from each group in a 1:3 ratio.ResultsIn total, 730 eligible patients were propensity matched, with 184 patients in Group A and 546 patients in Group B. Significant differences were not observed in the patient and tumor characteristics between Group A and Group B. At a median follow-up of 74.78 months (range 3.53–117.83 months), locoregional recurrence, distant failure and death were observed in 10.68, 11.10 and 16.03% of all patients, respectively. The estimated 5-year locoregional relapse–free survival, distant metastasis–free survival, progression-free survival and overall survival in the Group A versus Group B were 85.34% versus 89.79% (P = 0.156), 93.09% versus 85.61% (P = 0.012), 79.96% versus 77.99% (P = 0.117) and 88.91% versus 78.30% (P = 0.006), respectively.ConclusionsThis nimotuzumab-containing regimen resulted in improved long-term survival of III-IVb stage NPC patients and warrants further prospective evaluation.
The oncogene Gankyrin is expressed in testicular cancer and contributes to cisplatin sensitivity in embryonal carcinoma cells
Authors: Camacho-Moll Maria E. , Macdonald Joni , Looijenga L. H. J. , Rimmer Michael P. , Donat Roland , Marwick John A. , Shukla C. J. , Carragher Neil , Jørgensen Anne , Mitchell Rod T. 
Published: November 2019

Abstract
Background
Testicular germ cell cancer (TGCC) develops from pre-malignant germ neoplasia in situ (GCNIS) cells. GCNIS originates from fetal gonocytes (POU5F1+/MAGE-A4−), which fail to differentiate to pre-spermatogonia (POU5F1−/MAGE-A4+) and undergo malignant transformation. Gankyrin is an oncogene which has been shown to prevent POU5F1 degradation and specifically interact with MAGE-A4 in hepatocellular carcinoma (HCC) cells. We aimed to investigate the role of Gankyrin in progression from gonocyte to pre-invasive GCNIS and subsequent invasive TGCC.

Methods
We determined Gankyrin expression in human fetal testicular tissue (gestational weeks 9–20; n = 38), human adult testicular tissue with active spermatogenesis (n = 9), human testicular tissue with germ cell maturation delay (n = 4), testicular tissue from patients with pre-invasive GCNIS (n = 6), and invasive TGCC including seminoma (n = 6) and teratoma (n = 7). Functional analysis was performed in-vitro by siRNA knock-down of Gankyrin in the NTera2 cells (derived from embryonal carcinoma).

Results
Germ cell expression of Gankyrin was restricted to a sub-population of prespermatogonia in human fetal testes. Nuclear Gankyrin was also expressed in GCNIS cells of childhood and adult pre-invasive TGCC patients, and in GCNIS from seminoma and non-seminoma patients. Cytoplasmic expression was observed in seminoma tumour cells and NTera2 cells. Gankyrin knock-down in NTera2 cells resulted in an increase in apoptosis mediated via the TP53 pathway, whilst POU5F1 expression was unaffected. Furthermore, Gankyrin knock-down in NTera2 cells increased cisplatin sensitivity with an increase in cell death (13%, p < 0.05) following Gankyrin knock-down, when compared to cisplatin treatment alone, likely via BAX and FAS. Our results demonstrate that Gankyrin expression changes in germ cells during normal transition from gonocyte to prespermatogonia. In addition, changes in Gankyrin localisation are associated with progression of pre-invasive GCNIS to invasive TGCC. Furthermore, we found that Gankyrin is involved in the regulation of NTera2 cell survival and that a reduction in Gankyrin expression can modulate cisplatin sensitivity.

Conclusions
These results suggest that manipulation of Gankyrin expression may reduce the cisplatin dose required for the treatment of TGCC, with benefits in reducing dose-dependent side effects of chemotherapy. Further studies are required in order to assess the effects of modulating Gankyrin on GCNIS/TGCC using in vivo models.
Protective effect of Shenmai injection on doxorubicin-induced cardiotoxicity via regulation of inflammatory mediators
Authors: Zhang Sheng , You Zhen-Qiang , Yang Lin , Li Li-Li , Wu You-Ping , Gu Li-Qiang , Xin Yan-Fei 
Published: November 2019

Abstract
Background
Doxorubicin (DOX) is a chemotherapy drug for malignant tumors. The clinical application of DOX is limited due to its dosage relative cardiotoxicity. Oxidative damage and cardiac inflammation appear to be involved in DOX-related cardiotoxicity. Shenmai injection (SMI), which mainly consists of Panax ginsengC.A.Mey.and Ophiopogon japonicus (Thunb.) Ker Gawl, is widely used for the treatment of atherosclerotic coronary heart disease and viral myocarditis in China. In this study, we investigated the protective effect of Shenmai injection on doxorubicin-induced acute cardiac injury via the regulation of inflammatory mediators.

Methods
Male ICR mice were randomly divided into seven groups: control, DOX (10 mg/kg), SMI (5 g/kg), DOX with pretreatment with SMI (0.5 g/kg, 1.5 g/kg or 5 g/kg) and DOX with post-treatment with SMI (5 g/kg). Forty-eight hours after the last DOX administration, all mice were anesthetized for ultrasound echocardiography. Then, serum was collected for biochemical and inflammatory cytokine detection, and heart tissue was collected for histological and Western blot detection.

Results
A cumulative dose of DOX (10 mg/kg) induced acute cardiotoxicity in mice manifested by altered echocardiographic outcome, and increased tumor necrosis factor, interleukin 6 (IL-6), monocyte chemotactic protein 1, interferon-γ, and serum AST and LDH levels, as well as cardiac cytoplasmic vacuolation and myofibrillar disarrangement. DOX also caused the increase in the expression of IKK-α and iNOS and produced a large amount of NO, resulting in the accumulation of nitrotyrosine in the heart tissue. Pretreatment with SMI elicited a dose-dependent cardioprotective effect in DOX-dosed mice as evidenced by the normalization of serum inflammatory mediators, as well as improve dcardiac function and myofibril disarrangement.

Conclusions
SMI could recover inflammatory cytokine levels and suppress the expression of IKK-α and iNOS in vivo, which was increased by DOX. Overall, there was evidence that SMI could ameliorate DOX-induced cardiotoxicity by inhibiting inflammation and recovering heart dysfunction.
Mathematical modelling for health systems research: a systematic review of system dynamics and agent-based models
Authors: Cassidy Rachel , Singh Neha S. , Schiratti Pierre-Raphaël , Semwanga Agnes , Binyaruka Peter , Sachingongu Nkenda , Chama-Chiliba Chitalu Miriam , Chalabi Zaid , Borghi Josephine , Blanchet Karl 
Published: November 2019

Abstract
Background
Mathematical modelling has been a vital research tool for exploring complex systems, most recently to aid understanding of health system functioning and optimisation. System dynamics models (SDM) and agent-based models (ABM) are two popular complementary methods, used to simulate macro- and micro-level health system behaviour. This systematic review aims to collate, compare and summarise the application of both methods in this field and to identify common healthcare settings and problems that have been modelled using SDM and ABM.

Methods
We searched MEDLINE, EMBASE, Cochrane Library, MathSciNet, ACM Digital Library, HMIC, Econlit and Global Health databases to identify literature for this review. We described papers meeting the inclusion criteria using descriptive statistics and narrative synthesis, and made comparisons between the identified SDM and ABM literature.

Results
We identified 28 papers using SDM methods and 11 papers using ABM methods, one of which used hybrid SDM-ABM to simulate health system behaviour. The majority of SDM, ABM and hybrid modelling papers simulated health systems based in high income countries. Emergency and acute care, and elderly care and long-term care services were the most frequently simulated health system settings, modelling the impact of health policies and interventions such as those targeting stretched and under resourced healthcare services, patient length of stay in healthcare facilities and undesirable patient outcomes.

Conclusions
Future work should now turn to modelling health systems in low- and middle-income countries to aid our understanding of health system functioning in these settings and allow stakeholders and researchers to assess the impact of policies or interventions before implementation. Hybrid modelling of health systems is still relatively novel but with increasing software developments and a growing demand to account for both complex system feedback and heterogeneous behaviour exhibited by those who access or deliver healthcare, we expect a boost in their use to model health systems.
Improving the efficiency of soybean breeding with high-throughput canopy phenotyping
Authors: Moreira Fabiana Freitas , Hearst Anthony Ahau , Cherkauer Keith Aric , Rainey Katy Martin 
Published: November 2019

AbstractBackgroundIn the early stages of plant breeding programs high-quality phenotypes are still a constraint to improve genetic gain. New field-based high-throughput phenotyping (HTP) platforms have the capacity to rapidly assess thousands of plots in a field with high spatial and temporal resolution, with the potential to measure secondary traits correlated to yield throughout the growing season. These secondary traits may be key to select more time and most efficiently soybean lines with high yield potential. Soybean average canopy coverage (ACC), measured by unmanned aerial systems (UAS), is highly heritable, with a high genetic correlation with yield. The objective of this study was to compare the direct selection for yield with indirect selection using ACC and using ACC as a covariate in the yield prediction model (Yield|ACC) in early stages of soybean breeding. In 2015 and 2016 we grew progeny rows (PR) and collected yield and days to maturity (R8) in a typical way and canopy coverage using a UAS carrying an RGB camera. The best soybean lines were then selected with three parameters, Yield, ACC and Yield|ACC, and advanced to preliminary yield trials (PYT).ResultsWe found that for the PYT in 2016, after adjusting yield for R8, there was no significant difference among the mean performances of the lines selected based on ACC and Yield. In the PYT in 2017 we found that the highest yield mean was from the lines directly selected for yield, but it may be due to environmental constraints in the canopy growth. Our results indicated that PR selection using Yield|ACC selected the most top-ranking lines in advanced yield trials.ConclusionsOur findings emphasize the value of aerial HTP platforms for early stages of plant breeding. Though ACC selection did not result in the best performance lines in the second year of selections, our results indicate that ACC has a role in the effective selection of high-yielding soybean lines.
Nourseothricin N-acetyl transferase (NAT), a new selectable marker for nuclear gene expression in Chlamydomonas
Authors: Yang Xinjia , Peng Jialin , Pan Junmin 
Published: November 2019

AbstractBackgroundChlamydomonas reinhardtiiis a unicellular green alga, which is a most commonly used model organism for basic research and biotechnological applications. Generation of transgenic strains, which usually requires selectable markers, is instrumental in such studies/applications. Compared to other organisms, the number of selectable markers is limited in this organism. Nourseothricin (NTC) N-acetyl transferase (NAT) has been reported as a selectable marker in a variety of organisms but not includingC. reinhardtii. Thus, we investigated whetherNATwas useful and effective for selection of transgenic strains inC. reinhardtii. The successful use ofNATwould provide alterative choice for selectable markers in this organism and likely in other microalgae.ResultsC. reinhardtiiwas sensitive to NTC at concentrations as low as 5 µg/ml. There was no cross-resistance to nourseothricin in strains that had been transformed with hygromycin B and/or paromomycin resistance genes. A codon-optimizedNATfromStreptomyces nourseiwas synthesized and assembled into different expression vectors followed by transformation intoChlamydomonas. Around 500 transformants could be obtained by using 50 ng DNA on selection with 10 µg/ml NTC. The transformants exhibited normal growth rate and were stable at least for 10 months on conditions even without selection. We successfully tested thatNATcould be used as a selectable marker for ectopic expression ofIFT54-HA in strains with paromomycin and hygromycin B resistance markers. We further showed that the selection rate forIFT54-HA positive clones was greatly increased by fusingIFT54-HA toNATand processing with the FMDV 2A peptide.ConclusionsThis work represents the first demonstration of stable expression ofNATin the nuclear genome ofC. reinhardtiiand provides evidence thatNATcan be used as an effective selectable marker for transgenic strains. It provides alterative choice for selectable markers inC. reinhardtii.NATis compatible with paromomycin and hygromycin B resistance genes, which allows for multiple selections.
SIRT4 silencing in tumor-associated macrophages promotes HCC development via PPARδ signalling-mediated alternative activation of macrophages
Authors: Li Zhi , Li He , Zhao Zhi-Bo , Zhu Wei , Feng Pan-Pan , Zhu Xi-Wen , Gong Jian-Ping 
Published: November 2019

Abstract
Background
The activation of tumour-associated macrophages (TAMs) contributes to the progression of hepatocellular carcinoma (HCC). SIRT4 acts as a tumour suppressor of tumour growth by regulating cell metabolism, inflammation, and anti-tumourigenesis. However, the involvement of SIRT4 in the activation of TAMs is unknown. Based on previous findings, the expression of SIRT4 in distinct groups of TAMs as well as the effect of SIRT4 silencing on macrophage polarization was investigated.

Methods
The expression of SIRT4 in HCC tissues and peritumour tissues was tested by qRT-PCR, western blotting and histological analysis. A Kaplan-Meier survival curve was generated based on the expression of SIRT4 in the HCC samples. Next, immunofluorescence staining was used to evaluate distinct groups of TAMs in human HCC samples, and the expression of SIRT4 in M1 and M2 TAMs was examined by flow cytometry. A homograft mouse model was used to assess the effect of SIRT4 silencing in TAMs on the development of HCC cells.

Results
SIRT4 was significantly downregulated in HCC tumour tissues, and the expression of SIRT4 in peritumour tissues was positively associated with survival in patients. We further found that downregulation of SIRT4 was associated with increased macrophage infiltration and a high ratio of M2/M1 macrophages in HCC peritumour tissues. Using gene interference, we found that SIRT4 silencing in TAMs significantly modulated the alternative activation of macrophages and promoted in vitro and in vivo HCC cell growth. Mechanistically, we revealed that HCM restricted the expression of SIRT4 in macrophages and promoted alternative activation of macrophages via the FAO-PPARδ-STAT3 axis. Furthermore, we also revealed that elevated MCP-1 expression induced by SIRT4 downregulation was responsible for increased TAM infiltration in peritumour tissues.

Conclusions
Overall, our results demonstrate that downregulation of SIRT4 in TAMs modulates the alternative activation of macrophages and promotes HCC development via the FAO-PPARδ-STAT3 axis. These results could provide a new therapeutic target for the treatment of HCC.
Room4Birth - the effect of an adaptable birthing room on labour and birth outcomes for nulliparous women at term with spontaneous labour start: study protocol for a randomised controlled superiority trial in Sweden
Authors: Berg Marie , Goldkuhl Lisa , Nilsson Christina , Wijk Helle , Gyllensten Hanna , Lindahl Göran , Uvnäs Moberg Kerstin , Begley Cecily 
Published: November 2019

Abstract
Background
An important prerequisite for optimal healthcare is a secure, safe and comfortable environment. There is little research on how the physical design of birthing rooms affects labour, birth, childbirth experiences and birthing costs. This protocol outlines the design of a randomised controlled superiority trial (RCT) measuring and comparing effects and experiences of two types of birthing rooms, conducted in one labour ward in Sweden.

Methods/design
Following ethics approval, a study design was developed and tested for feasibility in a pilot study, which led to some important improvements for conducting the study. The main RCT started January 2019 and includes nulliparous women presenting to the labour ward in active, spontaneous labour and who understand either Swedish, Arabic, Somali or English. Those who consent are randomised on a 1:1 ratio to receive care either in a regular room (control group) or in a newly built birthing room designed with a person-centred approach and physical aspects (such as light, silencer, media installation offering programmed nature scenes with sound, bathtub, birth support tools) that are changeable according to a woman’s wishes (intervention group). The primary efficacy endpoint is a composite score of four outcomes: no use of oxytocin for augmentation of labour; spontaneous vaginal births (i.e. no vaginal instrumental birth or caesarean section); normal postpartum blood loss (i.e. bleeding < 1000 ml); and a positive overall childbirth experience (7–10 on a scale of 1–10). To detect a difference in the composite score of 8% between the groups we need 1274 study participants (power of 80% with significance level 0.05). Secondary outcomes include: the four variables in the primary outcome; other physical outcomes of labour and birth; women’s self-reported experiences (the birthing room, childbirth, fear of childbirth, health-related quality of life); and measurement of costs in relation to the hospital stay for mother and neonate. Additionally, an ethnographic study with participant observations will be conducted in both types of birthing rooms.

Discussion
The findings aim to guide the design of birthing rooms that contribute to optimal quality of hospital-based maternity care.

Trial registration
ClinicalTrials.gov NCT03948815. Registered 13 May 2019—retrospectively registered.
Determinants of late antenatal care follow up among pregnant women in Easter zone Tigray, Northern Ethiopia, 2018: unmatched case–control study
Authors: Weldearegawi Gebrehiwot Gebremariam , Teklehaimanot Berhane Fseha , Gebru Hirut Teame , Gebrezgi Znabu Asfaw , Tekola Kidanemaryam Berhe , Baraki Mulu Ftiwi 
Published: November 2019

Abstract
Objective
The purpose of the study was to identify determinants of late antennal care at first visit in health facilities of eastern zone of Tigray, Northern Ethiopia 2018.

Result
Women with unplanned pregnancy (AOR = 4.03, 95%, CI 1.56–5.67), Participants whose previous first antenatal care was after 16 weeks (AOR = 3.9, 95% CI 1.98–7.68), Participants did not accompanied by their partner for antenatal visit (AOR = 1.29, 95%, CI 1.05–4.67), women recognized their current pregnancy at 3 months or late (AOR = 4.7, 95%, CI 2.49–9.04) and participants provided adequate time for their previous antenatal care by health professionals (AOR = 0.461, 95% CI 0.342–0.875) were found the determinant factors of late antenatal care at first Visit. Hence family planning utilization, times of first visit antenatal, information flow and supporting by partners have a great role in improving antenatal care at first visit. There for responsible bodies should give focuses on utilization of family planning, increasing awareness of pregnancy symptoms and health provisional provide adequate time during visits.