bluuebunny/crossref_metadata_2025 huggingface dataset:
Prediction of fecal indicator organism concentrations in rivers: the shifting role of environmental factors under varying flow conditions
Authors: Herrig Ilona , Seis Wolfgang , Fischer Helmut , Regnery Julia , Manz Werner , Reifferscheid Georg , Böer Simone
Published: September 2019

Background

Fecal indicator organisms such as Escherichia coli, enterococci, and coliphages are important to assess, monitor, and predict microbial water quality in natural freshwater ecosystems. To improve predictive modelling of fecal indicators in surface waters, it is vital to assess the influence of autochthonous and allochthonous environmental factors on microbial water quality in riverine systems. To better understand how environmental conditions influence the fate of fecal indicators under varying weather conditions, the interdependencies of environmental parameters and concentrations of E. coli, intestinal enterococci, and somatic coliphages were studied at two rivers (Rhine and Moselle in Rhineland-Palatinate, Germany) over a period of 2 years that exhibited contrasting hydrological conditions. Both riverine sampling sites were subject to similar meteorological conditions based on spatial proximity, but differed in hydrodynamics and hydrochemistry, thus providing further insight into the role of river-specific determinants on fecal indicator concentrations. Furthermore, a Bayesian multiple linear regression approach that complies with the European Bathing Water Directive was applied to both rivers’ datasets to test model transferability and the validity of microbial water quality predictions in riverine systems under varying flow regimes.

Results

According to multivariate statistical analyses, rainfall events and high water discharge favored the input and dissemination of fecal indicators in both rivers. As expected, concentrations declined with rising global solar irradiance, water temperature, and pH. While variations in coliphage concentrations were predominantly driven by hydro-meteorological factors, bacterial indicator concentrations were strongly influenced by autochthonous biotic factors related to primary production. This was more pronounced under low flow conditions accompanied by strong phytoplankton blooms. Strong seasonal variations pointed towards bacterial indicator losses due to grazing activities. The Bayesian linear regression approach provided appropriate water quality predictions at the Rhine sampling site based on discharge, global solar irradiance, and rainfall as fecal indicator distributions were predominantly driven by hydro-meteorological factors.

Conclusions

Assessment of microbial water quality predictions implied that rivers characterized by strong hydrodynamics qualify for multiple linear regression models using readily measurable hydro-meteorological parameters. In rivers where trophic interactions exceed hydrodynamic influences, such as the Moselle, viral indicators may pose a more reliable response variable in statistical models.
Overlapping transcriptional expression response of wheat zinc-induced facilitator-like transporters emphasize important role during Fe and Zn stress
Authors: Sharma Shivani , Kaur Gazaldeep , Kumar Anil , Meena Varsha , Kaur Jaspreet , Pandey Ajay Kumar
Published: September 2019

Background

Hexaploid wheat is an important cereal crop that has been targeted to enhance grain micronutrient content including zinc (Zn) and iron (Fe). In this direction, modulating the expression of plant transporters involved in Fe and Zn homeostasis has proven to be one of the promising approaches. The present work was undertaken to identify wheat zinc-induced facilitator-like (ZIFL) family of transporters. The wheat ZIFL genes were characterized for their transcriptional expression response during micronutrient fluctuations and exposure to multiple heavy metals.

Results

The genome-wide analyses resulted in identification of fifteen putative TaZIFL-like genes, which were distributed only on Chromosome 3, 4 and 5. Wheat ZIFL proteins subjected to the phylogenetic analysis showed the uniform distribution along with rice, Arabidopsis and maize. In-silico analysis of the promoters of the wheat ZIFL genes demonstrated the presence of multiple metal binding sites including those which are involved in Fe and heavy metal homeostasis. Quantitative real-time PCR analysis of wheat ZIFL genes suggested the differential regulation of the transcripts in both roots and shoots under Zn surplus and also during Fe deficiency. Specifically, in roots, TaZIFL2.3, TaZIFL4.1, TaZIFL4.2, TaZIFL5, TaZIFL6.1 and TaZIFL6.2 were significantly up-regulated by both Zn and Fe. This suggested that ZIFL could possibly be regulated by both the nutrient stress in a tissue specific manner. When exposed to heavy metals, TaZIFL4.2 and TaZIFL7.1 show significant up-regulation, whereas TaZIFL5 and TaZIFL6.2 remained almost unaffected.

Conclusion

This is the first report for detailed analysis of wheat ZIFL genes. ZIFL genes also encode for transporter of mugineic acid (TOM) proteins, that are involved in the release of phytosiderophores to enhance Fe/Zn uptake. The detailed expression analysis suggests the varying expression patterns during development of wheat seedlings and also against abiotic/biotic stresses. Overall, this study will lay foundation to prioritize functional assessment of the candidate ZIFL as a putative TOM protein in wheat.
Mouse corticospinal system comprises different functional neuronal ensembles depending on their hodology
Authors: Olivares-Moreno Rafael , López-Hidalgo Mónica , Altamirano-Espinoza Alain , González-Gallardo Adriana , Antaramian Anaid , Lopez-Virgen Verónica , Rojas-Piloni Gerardo
Published: September 2019

Background

Movement performance depends on the synaptic interactions generated by coherent parallel sensorimotor cortical outputs to different downstream targets. The major outputs of the neocortex to subcortical structures are driven by pyramidal tract neurons (PTNs) located in layer 5B. One of the main targets of PTNs is the spinal cord through the corticospinal (CS) system, which is formed by a complex collection of distinct CS circuits. However, little is known about intracortical synaptic interactions that originate CS commands and how different populations of CS neurons are functionally organized. To further understand the functional organization of the CS system, we analyzed the activity of unambiguously identified CS neurons projecting to different zones of the same spinal cord segment using two-photon calcium imaging and retrograde neuronal tracers.

Results

Sensorimotor cortex slices obtained from transgenic mice expressing GCaMP6 funder the Thy1 promoter were used to analyze the spontaneous calcium transients in layer 5 pyramidal neurons. Distinct subgroups of CS neurons projecting to dorsal horn and ventral areas of the same segment show more synchronous activity between them than with other subgroups.

Conclusions

The results indicate that CS neurons projecting to different spinal cord zones segregated into functional ensembles depending on their hodology, suggesting that a modular organization of CS outputs controls sensorimotor behaviors in a coordinated manner.
Four-color multiplex real-time PCR assay prototype targeting azithromycin resistance mutations in Mycoplasma genitalium
Authors: Thellin Olivier , Elmoualij Benaïssa , Zorzi Willy , Jensen Jorgen S. , Close Renaud , Deregowski Valerie , Le Guern Fellous Muriel , Quatresooz Pascale
Published: September 2019

Background

The worldwide expansion of macrolide-resistant Mycoplasma genitalium (MG) in cases of genital infections has led to an increased recurrence rate of these infections after first-line azithromycin treatment. By detecting the presence of azithromycin-resistant MG, the patient’s antibiotic treatment can be targeted and the spread of resistance prevented. With this aim in mind, macrolide-resistance detection kits are helpful tools for the physician.

Methods

Azithromycin resistance mutations in MG are targeted using a four-color multiplex real-time RT-PCR assay. Tested targets include plasmid DNA (as positive controls) as well as macrolide-sensitive and macrolide-resistant genomic DNA from characterized cell lines and clinical samples.

Results

The analytical data presented here were generated from plasmid DNA and genomic RNA/DNA and include adaptation to an internal control, specificity between targets, specificity vs non-MG species, limit of detection (LoD) and interference studies (co-infection and endogenous substances). The clinical data were based on the application of the assay to clinical samples characterized by sequencing.

Conclusions

A new NAAT (nucleic acid amplification test) prototype has been developed in collaboration with the Diagenode s.a. company, this prototype targets MG and azithromycin-resistance mutations in that pathogen.
How to develop a sustainable telemedicine service? A Pediatric Telecardiology Service 20 years on - an exploratory study
Authors: Maia Mélanie Raimundo , Castela Eduardo , Pires António , Lapão Luís Velez
Published: September 2019

Background

Telemedicine services are promoting more access to healthcare. Portugal was an early adopter of telemedicine to overcome both its geological barriers and the shortage of healthcare professionals. The Pediatric Cardiology Service (PCS) at Coimbra University Hospital Centre (CHUC) has been using telemedicine to increase access and coverage since 1998. Their Pediatric Telecardiology Service has been daily connecting CHUC with 13 other Portuguese national hospitals, and regularly connecting with Portuguese-speaking African countries, through a teleconsultation platform.

Methods

This study aims at exploring the Pediatric Telecardiology Service’s evolution, through a comprehensive assessment of the PCS’s development, evolution and impact in public health, to better understand the critical factors for implementation and sustainability of telemedicine, in the context of healthcare services digitalization. A case study was performed, with cost-benefit, critical factors and organizational culture assessment. Finally, the Kingdon’s framework helped to understand the implementation and scale-up process and the role of policy-making.

Results

With the total of 32,685 out-patient teleconsultations, growing steadily from 1998 to 2016, the Pediatric Telecardiology Service has reached national and international recognition, being a pioneer and an active promotor of telemedicine. This telemedicine service has saved significant resources, about 1.1 million euros for the health system (e.g. in administrative and logistic costs) and approximately 419 euros per patient (considering an average of 1777 patients per year).

PCS presents a dominant “Clan” culture. The Momentum’s critical factors for telemedicine service implementation enabled us to understand how barriers were overcome (e.g. political forces). Willingness, perseverance and teamwork, allied with partnership with key stakeholders, were the foundation for professionals’ engagement and service networking development. Its positive results, new regulations and the increasing support from the hospital board, set up a window of opportunity to establish a sustainable telemedicine service.

Conclusion

The Pediatric Telecardiology Service enables real-time communication and the sharing of clinical information, overcoming many barriers (from geographical ones to shortage of healthcare professionals), improving access to specialized care both in Portugal and Africa.

Motivation and teamwork, and perseverance, were key for the Pediatric Telecardiology Service to tackle the window of opportunity which created conditions for sustainability.
Alpha-Terpineol production from an engineered Saccharomyces cerevisiae cell factory
Authors: Zhang Chuanbo , Li Man , Zhao Guang-Rong , Lu Wenyu
Published: September 2019

Background

Alpha-Terpineol (α-Terpineol), a C10 monoterpenoid alcohol, is widely used in the cosmetic and pharmaceutical industries. Construction Saccharomyces cerevisiae cell factories for producing monoterpenes offers a promising means to substitute chemical synthesis or phytoextraction.

Results

α-Terpineol was produced by expressing the truncated α-Terpineol synthase (tVvTS) from Vitis vinifera in S. cerevisiae. The α-Terpineol titer was increased to 0.83 mg/L with overexpression of the rate-limiting genes tHMG1, IDI1 and ERG20F96W-N127W. A GSGSGSGSGS linker was applied to fuse ERG20F96W-N127W with tVvTS, and expressing the fusion protein increased the α-Terpineol production by 2.87-fold to 2.39 mg/L when compared with the parental strain. In addition, we found that farnesyl diphosphate (FPP) accumulation by down-regulation of ERG9 expression and deletion of LPP1 and DPP1 did not improve α-Terpineol production. Therefore, ERG9 was overexpressed and the α-Terpineol titer was further increased to 3.32 mg/L. The best α-Terpineol producing strain LCB08 was then used for batch and fed-batch fermentation in a 5 L bioreactor, and the production of α-Terpineol was ultimately improved to 21.88 mg/L.

Conclusions

An efficient α-Terpineol production cell factory was constructed by engineering the S. cerevisiae mevalonate pathway, and the metabolic engineering strategies could also be applied to produce other valuable monoterpene compounds in yeast.
A signature of hypoxia-related factors reveals functional dysregulation and robustly predicts clinical outcomes in stage I/II colorectal cancer patients
Authors: Zou Yi-feng , Rong Yu-ming , Tan Ying-xin , Xiao Jian , Yu Zhao-liang , Chen Yu-feng , Ke Jia , Li Cheng-hang , Chen Xi , Wu Xiao-jian , Lan Ping , Lin Xu-tao , Gao Feng
Published: September 2019

Background

The hypoxic tumor microenvironment accelerates the invasion and migration of colorectal cancer (CRC) cells. The aim of this study was to develop and validate a hypoxia gene signature for predicting the outcome in stage I/II CRC patients that have limited therapeutic options.

Methods

The hypoxic gene signature (HGS) was constructed using transcriptomic data of 309 CRC patients with complete clinical information from the CIT microarray dataset. A total of 1877 CRC patients with complete prognostic information in six independent datasets were divided into a training cohort and two validation cohorts. Univariate and multivariate analyses were conducted to evaluate the prognostic value of HGS.

Results

The HGS consisted of 14 genes, and demarcated the CRC patients into the high- and low-risk groups. In all three cohorts, patients in the high-risk group had significantly worse disease free survival (DFS) compared with those in the low risk group (training cohort—HR = 4.35, 95% CI 2.30–8.23, P < 0.001; TCGA cohort—HR = 2.14, 95% CI 1.09–4.21, P = 0.024; meta-validation cohort—HR = 1.91, 95% CI 1.08–3.39, P = 0.024). Compared to Oncotype DX, HGS showed superior predictive outcome in the training cohort (C-index, 0.80 vs 0.65) and the validation cohort (C-index, 0.70 vs 0.61). Pathway analysis of the high- and low-HGS groups showed significant differences in the expression of genes involved in mTROC1, G2-M, mitosis, oxidative phosphorylation, MYC and PI3K–AKT–mTOR pathways (P < 0.005).

Conclusion

Hypoxic gene signature is a satisfactory prognostic model for early stage CRC patients, and the exact biological mechanism needs to be validated further.
Evaluation of Plasmodium falciparum MSP10 and its development as a serological tool for the Peruvian Amazon region
Authors: Bendezu Jorge , Villasis Elizabeth , Morales Ruiz Sandra , Garro Katherine , Infante Berónica , Gutierrez-Loli Renzo , Rodríguez Pamela , Fernández-Díaz Manolo , Gamboa Dionicia , Torres Katherine
Published: September 2019

Background

Different antigens are needed to characterize Plasmodium falciparum infection in terms of seroreactivity and targets for invasion inhibition, in order to guide and identify the proper use of such proteins as tools for the development of serological markers and/or as vaccine candidates.

Methods

IgG responses in 84 serum samples from individuals with P. falciparum infection [classified as symptomatic (Sym) or asymptomatic (Asym)], or acute Plasmodium vivax infection, from the Peruvian Amazon region, were evaluated by enzyme-linked immunosorbent assays specific for a baculovirus-produced recombinant protein P. falciparum Merozoite Surface Protein 10 (rMSP10) and for non-EGF region selected peptides of PfMSP10 selected by a bioinformatics tool (PfMSP10-1, PfMSP10-2 and PfMSP10-3). Monoclonal antibodies against the selected peptides were evaluated by western blotting, confocal microscopy and inhibition invasion assays.

Results

Seroreactivity analysis of the P. falciparum Sym- and Asym-infected individuals against rMSP10 showed a higher response as compared to the individuals with P. vivax acute infection. IgG responses against peptide PfMSP10-1 were weak. Interestingly high IgG response was found against peptide PfMSP10-2 and the combination of peptides PfMSP10-1 + PfMSP10-2. Monoclonal antibodies were capable of detecting native PfMSP10 on purified schizonts by western blot and confocal microscopy. A low percentage of inhibition of merozoite invasion of erythrocytes in vitro was observed when the monoclonal antibodies were compared with the control antibody against AMA-1 antigen. Further studies are needed to evaluate the role of PfMSP10 in the merozoite invasion.

Conclusions

The rMSP10 and the PfMSP10-2 peptide synthesized for this study may be useful antigens for evaluation of P. falciparum malaria exposure in Sym and Asym individuals from the Peruvian Amazon region. Moreover, these antigens can be used for further investigation of the role of this protein in other malaria-endemic areas.
Differential expression of var subgroups and PfSir2a genes in afebrile Plasmodium falciparum malaria: a matched case–control study
Authors: Gupta Himanshu , Galatas Beatriz , Matambisso Gloria , Nhamussua Lidia , Cisteró Pau , Bassat Quique , Casellas Aina , Macete Eusébio , Aponte John J. , Sacoor Charfudin , Alonso Pedro , Saúte Francisco , Guinovart Caterina , Aide Pedro , Mayor Alfredo
Published: September 2019

Background

Poor knowledge on the afebrile Plasmodium falciparum biology limits elimination approaches to target asymptomatic malaria. Therefore, the association of parasite factors involved in cytoadhesion, parasite multiplication and gametocyte maturation with afebrile malaria was assessed.

Methods

Plasmodium falciparum isolates were collected from febrile (axillary temperature ≥ 37.5 °C or a reported fever in the previous 24 h) and afebrile (fever neither at the visit nor in the previous 24 h) individuals residing in Southern Mozambique. var, PfSir2a and Pfs25 transcript levels were determined by reverse transcriptase quantitative PCRs (RT-qPCRs) and compared among 61 pairs of isolates matched by parasite density, age and year of sample collection.

Results

The level of varC and PfSir2a transcripts was higher in P. falciparum isolates from afebrile individuals (P ≤ 0.006), while varB and DC8 genes (P ≤ 0.002) were higher in isolates from individuals with febrile infections. After adjusting the analysis by area of residence, doubling the relative transcript unit (RTU) of varC and PfSir2a was associated with a 29.7 (95% CI 4.6–192.3) and 8.5 (95% CI 1.9–32.2) fold increases, respectively, of the odds of being afebrile. In contrast, doubling the RTU of varB and DC8 was associated with a 0.8 (95% CI 0.05–0.6) and 0.2 (95% CI 0.04–0.6) fold changes, respectively, of the odds of being afebrile. No significant differences were found for Pfs25 transcript levels in P. falciparum isolates from afebrile and febrile individuals.

Conclusions

var and gametocyte-specific transcript patterns in febrile and afebrile infections from southern Mozambique matched by age, parasite density and recruitment period suggest similar transmissibility but differential expression of variant antigens involved in cytoadhesion and immune-evasion.
Understanding and using patient experiences as evidence in healthcare priority setting
Authors: Rand Leah , Dunn Michael , Slade Ingrid , Upadhyaya Sheela , Sheehan Mark
Published: September 2019

Background

In many countries, committees make priority-setting decisions in order to control healthcare costs. These decisions take into account relevant criteria, including clinical effectiveness, cost-effectiveness, and need, and are supported by evidence usually drawn from clinical and economic studies. These sources of evidence do not include the specific perspective and information that patients can provide about the condition and treatment.

Methods

Drawing on arguments from political philosophy and ethics that are the ethical basis for many priority-setting bodies, the authors argue that criteria like need and its effects on patients and caregivers are best supported by evidence generated from patients’ experiences. Social sciences and mixed-methods research support the generation and collection of robust evidence.

Results

Patient experience is required for a decision-making process that considers all relevant evidence. For fair priority-setting, decision-makers should consider relevant evidence and reasons, so patient experience evidence should not be ignored. Patient experience must be gathered in a way that generates high quality and methodologically rigorous evidence. Established quantitative and qualitative methods can assure that evidence is systematic, adherent to quality standards, and valid. Patient, like clinical, evidence should be subject to a transparent review process.

Discussion

Considering all relevant evidence gives each person an equal opportunity at having their treatment funded. Patient experience gives context to the clinical evidence and also directly informs our understanding of the nature of the condition and its effects, including patients’ needs, how to meet them, and the burden of illness. Such evidence also serves to contextualise reported effects of the treatment. The requirement to include patient experience as evidence has important policy implications for bodies that make priority-setting decisions since it proposes that new types of evidence reviews are commissioned and considered.
WBNPMD: weighted bipartite network projection for microRNA-disease association prediction
Authors: Xie Guobo , Fan Zhiliang , Sun Yuping , Wu Cuiming , Ma Lei
Published: September 2019

Background

Recently, numerous biological experiments have indicated that microRNAs (miRNAs) play critical roles in exploring the pathogenesis of various human diseases. Since traditional experimental methods for miRNA-disease associations detection are costly and time-consuming, it becomes urgent to design efficient and robust computational techniques for identifying undiscovered interactions.

Methods

In this paper, we proposed a computation framework named weighted bipartite network projection for miRNA-disease association prediction (WBNPMD). In this method, transfer weights were constructed by combining the known miRNA and disease similarities, and the initial information was properly configured. Then the two-step bipartite network algorithm was implemented to infer potential miRNA-disease associations.

Results

The proposed WBNPMD was applied to the known miRNA-disease association data, and leave-one-out cross-validation (LOOCV) and fivefold cross-validation were implemented to evaluate the performance of WBNPMD. As a result, our method achieved the AUCs of 0.9321 and$$0.9173 \pm 0.0005$$0.9173±0.0005in LOOCV and fivefold cross-validation, and outperformed other four state-of-the-art methods. We also carried out two kinds of case studies on prostate neoplasm, colorectal neoplasm, and lung neoplasm, and most of the top 50 predicted miRNAs were confirmed to have an association with the corresponding diseases based on dbDeMC, miR2Disease, and HMDD V3.0 databases.

Conclusions

The experimental results demonstrate that WBNPMD can accurately infer potential miRNA-disease associations. We anticipated that the proposed WBNPMD could serve as a powerful tool for potential miRNA-disease associations excavation.
The role of radiotherapy in metaplastic breast cancer: a propensity score-matched analysis of the SEER database
Authors: Li Yongfeng , Chen Meng , Pardini Barbara , Dragomir Mihnea P. , Lucci Anthony , Calin George A.
Published: September 2019

Background

Only few studies, with small patient cohorts, have evaluated the effect of radiotherapy (RT) for metaplastic breast cancer (MBC). Hence, it is important to investigate the role of RT in MBC survival using a large population-database.

Methods

A retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER) from 1973 to 2015 was performed. We compared MBC patients with or without RT for overall survival (OS) and breast cancer-specific survival (BCSS) using univariate and multivariate Cox proportional hazard regressions before and after propensity score matching (PSM).

Results

From a total of 2267 patients diagnosed with MBC between 1998 and 2015, 1086 (47.9%) received RT. In the multivariate analysis before PSM, RT provided a better OS (HR 0.73; 95% CI 0.61–0.88; p = 0.001) and BCSS (HR 0.71; 95% CI 0.58–0.88; p = 0.002). Multivariate analyses after PSM (n = 1066) confirmed that patients receiving RT (n = 506) survived longer than those without RT (OS, HR 0.64; 95% CI 0.51–0.80; p < 0.001 and BCSS, HR 0.64; 95% CI 0.50–0.83; p = 0.001). A longer OS was observed when RT was given to older patients (p = 0.001) and in case of large tumor size (p = 0.002). Intriguingly, patients with N0 stage showed better OS after RT (HR 0.69, P = 0.012).

Conclusions

Our findings support the beneficial effect of RT for MBC patients. In particular, older patients or with large tumor size have a greater survival benefit from RT. In conclusion, we have assessed the importance of the use of RT in MBC as survival factor and this could lead to the development of guidelines for this rare sub-type of tumors.
RNA editing in the forefront of epitranscriptomics and human health
Authors: Christofi Theodoulakis , Zaravinos Apostolos
Published: September 2019

Post-transcriptional modifications have been recently expanded with the addition of RNA editing, which is predominantly mediated by adenosine and cytidine deaminases acting on DNA and RNA. Here, we review the full spectrum of physiological processes in which these modifiers are implicated, among different organisms. Adenosine to inosine (A-to-I) editors, members of the ADAR and ADAT protein families are important regulators of alternative splicing and transcriptional control. On the other hand, cytidine to uridine (C-to-U) editors, members of the AID/APOBEC family, are heavily implicated in innate and adaptive immunity with important roles in antibody diversification and antiviral response. Physiologically, these enzymes are present in the nucleus and/or the cytoplasm, where they modify various RNA molecules, including miRNAs, tRNAs apart from mRNAs, whereas DNA editing is also possible by some of them. The expansion of next generation sequencing technologies provided a wealth of data regarding such modifications. RNA editing has been implicated in various disorders including cancer, and neurological diseases of the brain or the central nervous system. It is also related to cancer heterogeneity and the onset of carcinogenesis. Response to treatment can also be affected by the RNA editing status where drug efficacy is significantly compromised. Studying RNA editing events can pave the way to the identification of new disease biomarkers, and provide a more personalised therapy to various diseases.
Heterogeneity of cancer-associated fibroblasts and roles in the progression, prognosis, and therapy of hepatocellular carcinoma
Authors: Yin Zeli , Dong Chengyong , Jiang Keqiu , Xu Zhe , Li Rui , Guo Kun , Shao Shujuan , Wang Liming
Published: September 2019

Hepatocellular carcinoma (HCC) is a lethal disease, and recurrence and metastasis are the major causes of death in HCC patients. Cancer-associated fibroblasts (CAFs), a major stromal cell type in the HCC microenvironment, promote HCC progression, and have gradually become a hot research topic in HCC-targeted therapy. This review comprehensively describes and discusses the heterogeneous tissue distribution, cellular origin, phenotype, and biological functions of HCC-associated fibroblasts. Furthermore, the possible use of CAFs for predicting HCC prognosis and in targeted therapeutic strategies is discussed, highlighting the critical roles of CAFs in HCC progression, diagnosis, and therapy.
Knowledge, perceptions and practices regarding schistosomiasis among women living in a highly endemic rural district in Zimbabwe: implications on infections among preschool-aged children
Authors: Mutsaka-Makuvaza Masceline Jenipher , Matsena-Zingoni Zvifadzo , Tshuma Cremance , Katsidzira Agnes , Webster Bonnie , Zhou Xiao-Nong , Midzi Nicholas
Published: September 2019

Background

Schistosomiasis primarily affects poor and neglected communities due to their lack of safe water and sanitation facilities. In an effort to improve intervention strategies, the present study investigated the association of socio-demographic characteristics of women with their existing knowledge, perceptions and practices (KPP) in five urogenital schistosomiasis endemic rural communities in Zimbabwe.

Methods

In February 2016, a cross sectional study was conducted in which 426 women in rural Madziwa area, Shamva District were interviewed using a pretested structured questionnaire seeking their KPP and socio-demographic characteristics. Logistic regression analysis was performed to identify socio-demographic factors associated with the KPP variables.

Results

Among the 426 participants, 93.7% knew about schistosomiasis, while 97.7 and 87.5% understood the disease transmission and methods for prevention, respectively. A significantly higher percentage of women aged ≥ 30 years compared to those < 30 years indicated that infertility is a complication of untreated chronic schistosomiasis (OR: 1.7, 95% CI: 0.9–3.0). Compared to women who had no history of infection, those who had been infected before were more likely to think that they were currently infected (OR: 3.7, 95% CI: 2.4–6.0). Bathing in unsafe water sources was more common in non-apostolic compared to apostolic followers (OR: 2.1, 95% CI: 1.2–3.7). Sole use of unsafe water for domestic purposes was significantly higher in uneducated women compared to the educated (OR: 1.8, 95% CI: 1.0–3.1). Compared to women of the Chakondora community, those in Chihuri, Nduna and Kaziro were more likely to know that dysuria is a symptom of schistosomiasis while those in Chihuri were also likely to allow young children to perform water contact activities (OR: 2.9, 95% CI: 1.5–5.5).

Conclusions

Despite the high level of schistosomiasis awareness, some women had inadequate knowledge about the mode of transmission and preventive measures for schistosomiasis. Socio-demographic characteristics were associated with the KPP of women. Thus, disease control efforts should consider socio-demographic factors, which may influence the knowledge, perceptions and practices of occupants in a given setting.
Histone chaperones and the Rrm3p helicase regulate flocculation in S. cerevisiae
Authors: Rowlands Hollie , Shaban Kholoud , Foster Barret , Proteau Yannic , Yankulov Krassimir
Published: September 2019

Background

Biofilm formation or flocculation is a major phenotype in wild type budding yeasts but rarely seen in laboratory yeast strains. Here, we analysed flocculation phenotypes and the expression ofFLOgenes in laboratory strains with various genetic backgrounds.

Results

We show that mutations in histone chaperones, the helicaseRRM3and the Histone DeacetylaseHDA1de-repress theFLOgenes and partially reconstitute flocculation. We demonstrate that the loss of repression correlates to elevated expression of severalFLOgenes, to increased acetylation of histones at the promoter ofFLO1and to variegated expression ofFLO11. We show that these effects are related to the activity of CAF-1 at the replication forks. We also demonstrate that nitrogen starvation or inhibition of histone deacetylases do not produce flocculation inW303andBY4742strains but do so in strains compromised for chromatin maintenance. Finally, we correlate the de-repression ofFLOgenes to the loss of silencing at the subtelomeric and mating type gene loci.

Conclusions

We conclude that the deregulation of chromatin maintenance and transmission is sufficient to reconstitute flocculation in laboratory yeast strains. Consequently, we propose that a gain in epigenetic silencing is a major contributing factor for the loss of flocculation phenotypes in these strains. We suggest that flocculation in yeasts provides an excellent model for addressing the challenging issue of how epigenetic mechanisms contribute to evolution.
Characterization of SCCmec, spa types and Multi Drug Resistant of methicillin-resistant Staphylococcus aureus isolates among inpatients and outpatients in a referral hospital in Shiraz, Iran
Authors: Hashemizadeh Zahra , Hadi Nahal , Mohebi Samane , Kalantar-Neyestanaki Davood , Bazargani Abdollah
Published: September 2019

Objectives

Molecular typing such as spa typing is used to control and prevent Staphylococcus aureus widespread in hospitals and communities. Hence, the aim of this study was to find the most common types of S. aureus strain circulating in Shiraz via spa and SCCmec typing methods.

Results

Total of 159 S. aureus isolates were collected from two tertiary hospitals in Shiraz. Isolates were identified by biochemical tests. Antimicrobial susceptibility tests were performed by standard disk diffusion method and then genetic analysis of bacteria was performed using SCCmec and spa typing. In this study 31.4% of the isolates were methicillin-resistant S. aureus. The majority of isolates were SSCmec type III. Spa type t030 was the most prominent type among MRSA strains. For the first time in Iran, spa003, t386, t1877, t314, t186, t1816, t304, t325, t345 were reported in this study. It was shown that there is a possibility that these spa types are native to this region. Our findings showed that SCCmec II, III and IV disseminate from hospital to community and vice versa. Thus, effective monitoring of MRSA in hospital and community is necessary.
A randomized control trial of phototherapy and 20% albumin versus phototherapy and saline in Kilifi, Kenya
Authors: Magai Dorcas N. , Mwaniki Michael , Abubakar Amina , Mohammed Shebe , Gordon Anne L. , Kalu Raphael , Mwangi Paul , Koot Hans M. , Newton Charles R.
Published: September 2019

Objective

The study evaluated the efficacy of phototherapy and 20% albumin infusion to reduce total serum bilirubin (TSB) in neonates with severe hyperbilirubinemia. The primary outcome was a reduction of TSB at the end of treatment. The secondary outcomes were the need for exchange transfusion, inpatient mortality, neurological outcomes at discharge, and development outcomes at 12-months follow-up.

Results

One hundred and eighteen neonates were randomly assigned to phototherapy and 20% albumin (n = 59) and phototherapy and saline (n = 69). The median age at admission was 5 (interquartile range (IQR) 3–6) days, and the median gestation was 36 (IQR 36–38) weeks. No significant differences were found in the change in TSB (Mann–WhitneyU =609,p = 0.98) and rate of change in TSB per hour after treatment (Mann–WhitneyU = 540,p = 0.39) between the two groups. There were no significant differences between the two groups in the proportion of participants who required exchange transfusion (χ2(2) = 0.36, p = 0.546); repeat phototherapy (χ2(2) = 2.37, p = 0.123); and those who died (χ2(2) = 0.92, p = 0.337).Trial registrationThe trial was registered in the International Standardized Randomized Controlled Trial Number (ISRCTN); trial registration number ISRCTN89732754.
Knowledge of obstetric danger signs and its associated factors among pregnant women in Angolela Tera District, Northern Ethiopia
Authors: Woldeamanuel Gashaw Garedew , Lemma Gorems , Zegeye Betregiorgis
Published: September 2019

Objective

Knowledge of danger signs of obstetric complications is the first essential step in accepting appropriate and timely referral to maternal and newborn care units. The objective of this study was to assess the knowledge of obstetric danger signs and associated factors among pregnant women in Angolela Tera district, Northern Ethiopia. A community based cross sectional study was conducted among 563 pregnant women who were selected by multi-stage cluster sampling technique. Data were collected using a pre-tested and interviewer administered structured questionnaire. Descriptive statistics and binary logistic regression analysis were performed using statistical package for social sciences (SPSS) version 23.

Results

A total of 563 pregnant women were included in the study. About 211 (37.5%) women were knowledgeable about obstetric danger signs. Attending formal education, urban residence, time taken less than 20 min to reach health facility on foot, two or more history of pregnancies and receiving health education were found to be significantly associated with being knowledgeable about obstetric danger signs. A significant proportion of pregnant women in the study area were not knowledgeable about obstetric danger signs. Hence, continuous health education and appropriate counseling to pregnant mothers should be performed.
Labor pain control and associated factors among women who gave birth at Leku primary hospital, southern Ethiopia
Authors: Siyoum Melese , Mekonnen Shewangizaw
Published: September 2019

Objective

To assess labor pain control and associated factors among women who give birth at Leku primary hospital, southern Ethiopia, 2018/19. A systematic random sampling technique was used to select 404 mothers who gave birth at Leku hospital during the data collection period. Data were collected by two first degree midwives immediately after delivery using Labor Agentry Scale (LAS).

Results

In this study, 404 mothers were participated making the response rate of 100%. Among the participants, 104 (25.7%) of mothers reported Mild control of labor pain. Maternal age of 19 to 24 year AOR = 5.85 (95% CI 2.14, 15.98), being farmer AOR = 2.5 (1.14, 5.57), primi-para AOR = 0.13 (0.06, 0.3), good family support AOR = 2.8 (1.49, 5.3), short duration of labor (< 12 h) AOR = 3.2 (1.65, 6.23) and history of pregnancy loss AOR = 0.06 (0.03, 0.14) were significantly associated with greater control of labor pain. In general, compared to other studies, the level of labor pain control is good in this study area. Enhancing factors of labor pain control have to be strengthened to increase greater control of labor pain. Qualitative research is highly recommended to identify cultural factors related to labor pain control and management.
Predictors of very preterm births (born between 23 and 29 weeks’ gestation) at a tertiary care center in Karachi, Pakistan: additional multivariate analyses on data from primary cohort
Authors: Yakoob Mohammad Yawar
Published: September 2019

Objective

Previously, we have published univariate analyses on a cohort of all singleton, very preterm infants (N = 101) born between 23 and 29 weeks of gestation during January 01, 1998 to June 30, 2003 at The Aga Khan University Hospital in Karachi, Pakistan. Our main objective was to extend these analyses to multivariate logistic regression models and report odds ratios (ORs) for univariate and multivariate analyses. All variables in univariate were included in multivariate models.

Results

The survival incidences were 0% at 23, 16.7% at 24, 40.0% at 25, 30.0% at 26, 33.3% at 27, 68.8% at 28 and 83.9% at 29 weeks of gestation. In univariate analyses, gestational age, birth-weight and mode of delivery (cesarean-section had higher survival compared to vaginal) were statistically significant predictors of survival (P ≤ 0.001 each). Other variables that also included antenatal steroids did not achieve significance. However, in complete-case multivariate analyses, only gestational age (per week) was associated with survival (OR = 2.5, 95% CI 1.1–5.5, P = 0.03); birth-weight (per 100 g) and C-section were not associated-1.2, 0.88–1.6, P = 0.26 and 2.4, 0.48–12.2, P = 0.28. Antenatal steroid use, maternal age, year of birth, parity, history of preterm delivery, hemoglobin levels, complications and time of birth remained not associated.
Risk factors for mortality of patients with ceftriaxone resistant E. coli bacteremia receiving carbapenem versus beta lactam/beta lactamase inhibitor therapy
Authors: Nasir Nosheen , Ahmed Sara , Razi Samrah , Awan Safia , Mahmood Syed Faisal
Published: September 2019

Objective

Extended spectrum β-lactamases (ESBL) producing Enterobacteriaceae predominantly E. coli and K. pneumoniae bacteremia have limited treatment options and high mortality. The objective was to determine the risk factors for in-hospital mortality particularly treatment with carbapenem versus beta lactam/beta lactamase combination (BL/BLI) in patients with ceftriaxone resistant E. coli bacteremia. A retrospective cohort study was conducted at the Aga Khan University, Karachi, Pakistan. Adult patients with sepsis and monomicrobial ceftriaxone resistant E. coli bacteremia were enrolled. Factors associated with mortality in patients were determined using logistic regression analysis.

Results

Mortality rate was 37% in those empirically treated with carbapenem compared to 20% treated with BL/BLI combination therapy (p-value: 0.012) and was 21% in those treated with a carbapenem compared to 13% in patients definitively treated with BL/BLI combination therapy (p-value: 0.152). In multivariable logistic regression analysis, only Pitt bacteremia score of ≥ four was significantly associated with mortality (OR: 7.7 CI 2.6–22.8) while a urinary source of bacteremia was protective (OR: 0.26 CI 0.11–0.58). In-hospital mortality in patients with Ceftriaxone resistant E. coli bacteremia did not differ in patients treated with either a carbapenem or BL/BLI combination. However, Pitt bacteremia score of ≥ 4 was strongly associated with mortality.
Ki67 index in intrinsic breast cancer subtypes and its association with prognostic parameters
Authors: Hashmi Atif Ali , Hashmi Kashif Ali , Irfan Muhammad , Khan Saadia Mehmood , Edhi Muhammad Muzzammil , Ali Javaria Parwez , Hashmi Shumaila Kanwal , Asif Huda , Faridi Naveen , Khan Amir
Published: September 2019

Objectives

Ki67 is the most commonly used marker to evaluate proliferative index in breast cancer, however no cutoff values have been clearly defined for high ki67 index. Cancer management should be according to loco-regional profile; therefore, we aimed to determine ki67 index in 1951 cases of intrinsic breast cancer subtypes and its association with other prognostic parameters in our set up.

Results

Triple negative breast cancers showed highest ki67 index (mean 50.9 ± 23.7%) followed by Her2neu (mean 42.6 ± 21.6%) and luminal B cancers (mean 34.9 ± 20.05%). Metaplastic and medullary breast cancers significantly showed higher ki67 index as compared to ductal carcinoma, NOS. No significant association of ki67 index was noted with any of the histologic parameters in different subtypes of breast cancer expect for tumor grade. Although, ki67 index is a valuable biomarker in breast cancer, however no independent prognostic significance of ki67 could be established in our study.
Comparative analysis of IGFBP-3 gene sequence in Egyptian sheep, cattle, and buffalo
Authors: Saleh Ahmed. A. , Rashad Amr M. A. , Hassanine Nada. N. A. M. , Sharaby Mahmoud A. , Zhao Yongju
Published: September 2019

Objective

A total of 205 animals from four Egyptian livestock species; cattle (n = 18), buffaloes (n = 12), sheep (n = 150) and goats (n = 25) were used in this study to detect polymorphism and perform comparative analysis for IGFBP-3 gene using DNA sequencing and (PCR–RFLP).

Results

The amplified fragments were found to be of length 654 bp in sheep, 651 bp in cattle and 655 bp in buffalo. For Falahy goats, PCR was performed to amplify a 316 bp fragment from exon 2 of the IGFBP-3 gene. The digestion of 654 bp withHaeIIIrestriction enzyme yielded a single restriction pattern for goats, while for cattle, 3 genotypes were identified; (AA), (AB), and (BB). Moreover, for buffalo one genotype (AA) only was found withHaeIIIandTaqIrestriction enzymes, separately. Also, the digestion profile for goats withHaeIIIrevealed one pattern only. Nucleotide sequencing of the amplified fragments of IGFBP-3 gene in sheep, cattle, buffalo, and goat was submitted to the NCBI GenBank (Accession no. MG738671.1, MG738673.1, MG738674.1, and MG738672.1, respectively). The nucleotide sequencing analysis indicated similarity percentages in IGFBP-3 gene fragments of 88.54, 89.63 and 95.06% between “sheep and cattle”, “sheep and buffalo”, and “cattle and buffalo”, respectively.
Bacterial contamination and antimicrobial susceptibility patterns of intensive care units medical equipment and inanimate surfaces at Ayder Comprehensive Specialized Hospital, Mekelle, Northern Ethiopia
Authors: Darge Addis , Kahsay Atsebaha Gebrekidan , Hailekiros Haftamu , Niguse Selam , Abdulkader Mahmud
Published: September 2019

Objective

To determine bacterial contaminants and their antimicrobial susceptibility patterns from medical equipment and inanimate surfaces.

Results

Of 130 swabs, 115 (88.5%) swabs were culture positive, of which contaminated medical equipment and inanimate surfaces account 70 (83.3%) and 45 (97.8%), respectively. All the swabs collected from sphygmomanometer, bedside table, computer and computer standing tables were 100% contaminated with bacteria. From the culture-positive swabs, a total of 171 bacterial isolates were identified, out of which 117 (68.4%) and 54 (31.6%) isolates were gram-positive and gram-negative, respectively. Most isolates (82%) were resistant to ampicillin and 13%, 8.6%, and 14% was observed in ciprofloxacin, gentamicin, and tetracycline respectively. Multi-drug resistant was observed inEscherichia coli(72.7%) andStaphylococcus aureus(58.7%).
Objectively-measured physical activity patterns and longitudinal weight category status in a rural setting
Authors: Cook Ian
Published: September 2019

Objectives

To investigate the relationship between longitudinal weight-change and objectively-measured physical activity (PA) in a rural African setting in 143 adults (≥ 30 years), using data from two cross-sectional surveys, separated by approximately 10 years. Participants were categorised into three weight-change groups (Weight-loss: ≥ 25 kg m−2→ < 25 kg m−2; Weight-gain: < 25 kg m−2→ ≥ 25 kg m−2; Weight-stability: remained < 25 kg m−2 or ≥ 25 kg m−2). Daily ambulation and activity energy expenditure (AEE), measured in the 2005–2007 health survey, was examined across the weight-change groups. Using the daily AEE data, the proportion of those in the weight-change groups, meeting or not meeting two PA guidelines (150- and 420 min week−1), was examined.

Results

Weight-change was found in 18.2% of the sample. There was no significant overall body mass change (+ 1.2 kg, p = 0.1616). However, there was significant change in body mass in the weight-gain (+ 15.2 kg) and weight-loss (− 10.8 kg) groups (p ≤ 0.0011). Nearly 90% of those who gained weight met the 150 min week−1 guideline. A significantly greater proportion of the weight-stable group (< 25 kg m−2) met the 420 min week−1 guideline (p < 0.05). Ambulatory level was high irrespective of weight group, although the weight-stable group (< 25 kg m−2) approached 15,000 steps day−1. There was an inconsistent and weak association between PA and weight-change in this group.