bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using health facility-based serological surveillance to predict receptive areas at risk of malaria outbreaks in elimination areas
Authors: Surendra Henry , Supargiyono  , Ahmad Riris A. , Kusumasari Rizqiani A. , Rahayujati Theodola B. , Damayanti Siska Y. , Tetteh Kevin K. A. , Chitnis Chetan , Stresman Gillian , Cook Jackie , Drakeley Chris 
Published: January 2020

Abstract
Background
In order to improve malaria burden estimates in low transmission settings, more sensitive tools and efficient sampling strategies are required. This study evaluated the use of serological measures from repeated health facility-based cross-sectional surveys to investigate Plasmodium falciparum and Plasmodium vivax transmission dynamics in an area nearing elimination in Indonesia.

Methods
Quarterly surveys were conducted in eight public health facilities in Kulon Progo District, Indonesia, from May 2017 to April 2018. Demographic data were collected from all clinic patients and their companions, with household coordinates collected using participatory mapping methods. In addition to standard microscopy tests, bead-based serological assays were performed on finger-prick bloodspot samples from 9453 people. Seroconversion rates (SCR, i.e. the proportion of people in the population who are expected to seroconvert per year) were estimated by fitting a simple reversible catalytic model to seroprevalence data. Mixed effects logistic regression was used to examine factors associated with malaria exposure, and spatial analysis was performed to identify areas with clustering of high antibody responses.

Results
Parasite prevalence by microscopy was extremely low (0.06% (95% confidence interval 0.03–0.14, n = 6) and 0 for P. vivax and P. falciparum, respectively). However, spatial analysis of P. vivax antibody responses identified high-risk areas that were subsequently the site of a P. vivax outbreak in August 2017 (62 cases detected through passive and reactive detection systems). These areas overlapped with P. falciparum high-risk areas and were detected in each survey. General low transmission was confirmed by the SCR estimated from a pool of the four surveys in people aged 15 years old and under (0.020 (95% confidence interval 0.017–0.024) and 0.005 (95% confidence interval 0.003–0.008) for P. vivax and P. falciparum, respectively). The SCR estimates in those over 15 years old were 0.066 (95% confidence interval 0.041–0.105) and 0.032 (95% confidence interval 0.015–0.069) for P. vivax and P. falciparum, respectively.

Conclusions
These findings demonstrate the potential use of health facility-based serological surveillance to better identify and target areas still receptive to malaria in an elimination setting. Further implementation research is needed to enable integration of these methods with existing surveillance systems.
Improving phytosterol biotransformation at low nitrogen levels by enhancing the methylcitrate cycle with transcriptional regulators PrpR and GlnR of Mycobacterium neoaurum
Authors: Zhang Yang , Zhou Xiuling , Wang Xuemei , Wang Lu , Xia Menglei , Luo Jianmei , Shen Yanbing , Wang Min 
Published: January 2020

Abstract
Background
Androstenedione (AD) is an important steroid medicine intermediate that is obtained via the degradation of phytosterols by mycobacteria. The production process of AD is mainly the degradation of the phytosterol aliphatic side chain, which is accompanied by the production of propionyl CoA. Excessive accumulation of intracellular propionyl-CoA produces a toxic effect in mycobacteria, which restricts the improvement of production efficiency. The 2-methylcitrate cycle pathway (MCC) plays a significant role in the detoxification of propionyl-CoA in bacterial. The effect of the MCC on phytosterol biotransformation in mycobacteria has not been elucidated in detail. Meanwhile, reducing fermentation cost has always been an important issue to be solved in the optimizing of the bioprocess.

Results
There is a complete MCC in Mycobacterium neoaurum (MNR), prpC, prpD and prpB in the prp operon encode methylcitrate synthase, methylcitrate dehydratase and methylisocitrate lyase involved in MCC, and PrpR is a specific transcriptional activator of prp operon. After the overexpression of prpDCB and prpR in MNR, the significantly improved transcription levels of prpC, prpD and prpB were observed. The highest conversion ratios of AD obtained by MNR-prpDBC and MNR-prpR increased from 72.3 ± 2.5% to 82.2 ± 2.2% and 90.6 ± 2.6%, respectively. Through enhanced the PrpR of MNR, the in intracellular propionyl-CoA levels decreased by 43 ± 3%, and the cell viability improved by 22 ± 1% compared to MNR at 96 h. The nitrogen transcription regulator GlnR repressed prp operon transcription in a nitrogen-limited medium. The glnR deletion enhanced the transcription level of prpDBC and the biotransformation ability of MNR. MNR-prpR/ΔglnR was constructed by the overexpression of prpR in the glnR-deleted strain showed adaptability to low nitrogen. The highest AD conversion ratio by MNR-prpR/ΔglnR was 92.8 ± 2.7% at low nitrogen level, which was 1.4 times higher than that of MNR.

Conclusion
Improvement in phytosterol biotransformation after the enhancement of propionyl-CoA metabolism through the combined modifications of the prp operon and glnR of mycobacteria was investigated for the first time. The overexpress of prpR in MNR can increase the transcription of essential genes (prpC, prpD and prpB) of MCC, reduce the intracellular propionyl-CoA level and improve bacterial viability. The knockout of glnR can enhance the adaptability of MNR to the nitrogen source. In the MNRΔglnR strain, overexpress of prpR can achieve efficient production of AD at low nitrogen levels, thus reducing the production cost. This strategy provides a reference for the economic and effective production of other valuable steroid metabolites from phytosterol in the pharmaceutical industry.
Ubiquitin-specific protease 7 is a drug-able target that promotes hepatocellular carcinoma and chemoresistance
Authors: Zhang Wei , Zhang Jingxin , Xu Chenzhou , Zhang Shiqing , Bian Saiyan , Jiang Feng , Ni Wenkai , Qu Lishuai , Lu Cuihua , Ni Runzhou , Fan Yihui , Xiao Mingbing , Liu Jinxia 
Published: January 2020

Abstract
Background
Ubiquitin-specific protease 7 (USP7) is a de-ubiquitin enzyme that plays an essential role in multiple cancers and becomes a target for treatment. However, the role of USP7 and its therapeutic value for HCC remains unclear.

Methods
USP7 expression was examined in HCC tissues by western blot and immunohistochemistry. The correlation of USP7 and HCC prognosis was analyzed by Kaplan–Meier survival method. Mass spectrometry was determined and cell proliferation and tumorigenicity assays were conducted in vitro and in vivo treated by P22077 and sgRNA-USP7.

Results
USP7 expression was significantly increased in HCC and associated with its progression. Interestingly, many HCC cells are sensitive to USP7 inhibition by using P22077. P22077 treatment not only induced cell death but also inhibited cell proliferation and migration in Huh7 and SK-Hep1 cells. In a xenograft model, P22077 efficiently inhibited tumor growth. In chemo-resistant HCC cells, P22077 decreased cell sensitivity to chemotherapy. In addition, mass spectrometry reveals 224 of significantly changed proteins upon P22077 treatment.

Conclusions
We demonstrate a critical role of USP7 in HCC devolvement and chemoresistance. Disruption of USP7 function results in dis-regulated several key biological processes and subsequently activates BAX. USP7 might be a novel and drug-able target in HCC.
Demonstration of anti-tumour bystander killing with prodrug-preloaded suicide gene-engineered tumour cells: a potential improvement for cancer therapeutics
Authors: Zweiri Jehad , Christmas Stephen E. 
Published: January 2020

Abstract
Background
Therapeutic approaches for cancer rely on careful consideration of finding the optimal way of delivering the pro-drug for cellular-based cancer treatment. Cell lines and cell cultures have been used in these studies to compare the in vitro and in vivo efficacy of autologous vs. allogeneic tumour cellular gene therapy. Here we have investigated and are reporting for the first time the effect of prodrug ganciclovir (GCV)-preloading (pre-treatment) in suicide gene therapy of cancer.

Methods
This study examines the effect of GCV-preloading (pre-treatment) on a range of tumour cell lines in conjunction with suicide gene therapy of cancer. To determine the efficacy of this modality, a series of in vitro and in vivo experiments were conducted using genetically modified and unmodified tumour cell lines.

Results
Following co-culture of herpes simplex virus thymidine kinase (HSV-TK) modified tumour cells and unmodified tumour cells both in vitro and in vivo, GCV-preloading (pre-treatment) of TK-modified human and mouse mesothelioma cells and ovarian tumour cells allowed them to mediate efficiently bystander killing of neighbouring unmodified tumour cells in vitro. In contrast, GCV-preloading of TK-modified human and mouse mesothelioma cells and ovarian tumour cells abolished their in vivo ability to induce bystander killing of unmodified tumour cells, although there was some tumour regression compared to control groups but this was not statistically significant. These results suggest that preloading TK modified tumour cells with GCV needs further study to define the most effective strategy for an in vivo application to retain their bystander killing potential after exposure to lethal doses of GCV in vitro.

Conclusions
This study highlights the promising possibility of improving the efficacy of pro-drug system to prevent any damage to the immune system and enhancing this type of suicide gene therapy of cancer, as well as the need for further studies to explore the discrepancies between in vitro and in vivo results.
Sustainable under nutrition reduction program and dietary diversity among children’s aged 6–23 months, Northwest Ethiopia: Comparative cross-sectional study
Authors: Worku Tigist , Gonete Kedir Abdela , Muhammad Esmael Ali , Atnafu Asmamaw 
Published: January 2020

Abstract
Introduction
Adequate dietary diversity is vital for the survival, growth and development of infants and children. Inadequate dietary diversity is the major cause of micronutrient deficiency in Sub-saharan Africa, including Ethiopia, where only less than one-fourth of the children aged 6–23 months obtain adequate diversified diet. Thus country implemented a strategy known as the Sustainable Undernutrtion Reduction (SUR) programs to alleviate the problem. However, empirical evidences are scarce on the impact of the program on children aged 6–23 months. Therefore, this study aimed to compare the level of dietary diversity among children aged 6–23 months in districts covered and not covered by SURE program in West Gojjam zone.

Methods
A community based comparative cross-sectional study was conducted in three districts of West Gojjam zone, Ethiopia, from February 29 to April 20, 2019. A total of 832 mother and child pairs were selected by the simple random sampling technique. A pretested and structured interviewer-administered questionnaire was used to collect data. A binary logistic regression model was fitted to identify factors associated with dietary diversity. Crude odds and adjusted odds ratios with 95% confidence intervals (CI) were calculated to assess the strength of associations and significance of the identified factors for dietary diversity score.

Result
The overall proportion of adequate dietary diversity among children aged 6–23 months was 29.9% (95% CI: 27.0–33.0), whereas in SURE covered and uncovered districts it was 33.4% (95%CI: 29.0–38.and 26.4%(95% CI: 22.0, 31.0), respectively. ANC (Antenatal care) (AOR = 1.7; 95% CI: 1.16, 2.55) and postnatal care services (AOR = 2.1; 95% CI: 1.38, 3.28), participating in food preparation programs (AOR = 1.9; 95% CI: 1.19, 2.96), GMP (AOR = 2.74,95%CI:1.80, 4.18), vitamin A supplementation (AOR = 2.10,95%CI:1.22, 3.61) and household visits by health extension workers (AOR = 2.0; 95% CI: 1.25, 3.21) were significantly associated with dietary diversity.

Conclusion
The proportion of adequate dietary diversity was higher among children in the program than those out of the program. ANC visits, PNC follow-ups, women’s participating in food preparation programs and household visits by health extension workers were significantly associated with dietary diversity. Therefore, and strengthening and scaling up the program to non covered districts and providing health and nutrition counseling on Infant and Young Child Feeding (IYCF) during ANC and PNC services are recommended for achieving the recommended dietary diversity.
The synthetic steroid tibolone exerts sex-specific regulation of astrocyte phagocytosis under basal conditions and after an inflammatory challenge
Authors: Crespo-Castrillo Andrea , Garcia-Segura Luis-Miguel , Arevalo Maria-Angeles 
Published: January 2020

Abstract
Background
Tibolone is a synthetic steroid used in clinical practice for the treatment of climacteric symptoms and osteoporosis. Active metabolites of tibolone, generated in target tissues, have an affinity for estrogen and androgen receptors. Astrocytes are direct targets for estrogenic compounds and previous studies have shown that tibolone protects brain cortical neurons in association with a reduction in reactive astrogliosis in a mouse model of traumatic brain injury. Since phagocytosis is a crucial component of the neuroprotective function exerted by astrocytes, in the present study, we have assessed whether tibolone regulates phagocytosis in primary astrocytes incubated with brain-derived cellular debris.

Methods
Male and female astrocyte cell cultures were obtained from newborn (P0-P2) female and male Wistar rats. Astrocytic phagocytosis was first characterized using carboxylate beads, Escherichia coli particles, or brain-derived cellular debris. Then, the effect of tibolone on the phagocytosis of Cy3-conjugated cellular debris was quantified by measuring the intensity of Cy3 dye-emitted fluorescence in a given GFAP immunoreactive area. Before the phagocytosis assays, astrocytes were incubated with tibolone in the presence or absence of estrogen or androgen receptor antagonists or an inhibitor of the enzyme that synthesizes estradiol. The effect of tibolone on phagocytosis was analyzed under basal conditions and after inflammatory stimulation with lipopolysaccharide.

Results
Tibolone stimulated phagocytosis of brain-derived cellular debris by male and female astrocytes, with the effect being more pronounced in females. The effect of tibolone in female astrocytes was blocked by a selective estrogen receptor β antagonist and by an androgen receptor antagonist. None of these antagonists affected tibolone-induced phagocytosis in male astrocytes. In addition, the inhibition of estradiol synthesis in the cultures enhanced the stimulatory effect of tibolone on phagocytosis in male astrocytes but blocked the effect of the steroid in female cells under basal conditions. However, after inflammatory stimulation, the inhibition of estradiol synthesis highly potentiated the stimulation of phagocytosis by tibolone, particularly in female astrocytes.

Conclusions
Tibolone exerts sex-specific regulation of phagocytosis in astrocytes of both sexes, both under basal conditions and after inflammatory stimulation.
Age-specific differences in the time-frequency representation of surface electromyographic data recorded during a submaximal cyclic back extension exercise: a promising biomarker to detect early signs of sarcopenia
Authors: Habenicht R. , Ebenbichler G. , Bonato P. , Kollmitzer J. , Ziegelbecker S. , Unterlerchner L. , Mair P. , Kienbacher T. 
Published: January 2020

Abstract
Purpose
Motivated by the goal of developing new methods to detect early signs of sarcopenia, we investigated if surface electromyographic (SEMG) data recorded during the performance of cyclic, submaximal back extensions are marked by age-specific differences in their time and frequency characteristics. Furthermore, day-to-day retest reliability of the EMG measures was examined.

Methods
A total of 86 healthy volunteers used a back dynamometer to perform a series of three maximal voluntary contractions (MVC) consisting of isometric back extensions, followed by an isometric back extension at 80% MVC, and finally 25 slow cyclic back extensions at 50% MVC. SEMG data was recorded bilaterally at L1, L2, and L5 from the iliocostalis lumborum, longissimus, and multifidus muscles, respectively. Tests were repeated two days and six weeks later. A linear mixed-effects model with fixed effects “age, sex, test number” and the random effect “person” was performed to investigate age-specific differences in both the initial value and the time-course (as defined by the slope of the regression line) of the root mean square (RMS-SEMG) values and instantaneous median frequency (IMDF-SEMG) values calculated separately for the shortening and lengthening phases of the exercise cycles. Generalizability Theory was used to examine reliability of the EMG measures.

Results
Back extensor strength was comparable in younger and older adults. The initial value of RMS-SEMG and IMDF-SEMG as well as the RMS-SEMG time-course did not significantly differ between the two age groups. Conversely, the IMDF-SEMG time-course showed more rapid changes in younger than in older individuals. Absolute and relative reliability of the SEMG time-frequency representations were comparable in older and younger individuals with good to excellent relative reliability but variable absolute reliability levels.

Conclusions
The IMDF-SEMG time-course derived from submaximal, cyclic back extension exercises performed at moderate effort showed significant differences in younger vs. older adults even though back extension strength was found to be comparable in the two age groups. We conclude that the SEMG method proposed in this study has great potential to be used as a biomarker to detect early signs of sarcopenic back muscle function.
Assessment of respiratory and systemic toxicity of Benzalkonium chloride following a 14-day inhalation study in rats
Authors: Choi Hye-Yeon , Lee Yong-Hoon , Lim Cheol-Hong , Kim Yong-Soon , Lee In-Seop , Jo Ji-Min , Lee Ha-Young , Cha Hyo-Geun , Woo Hee Jong , Seo Dong-Seok 
Published: January 2020

Abstract
Background
Although biocides at low concentrations have been used to control pests, they can be more harmful than industrial chemicals as humans are directly and frequently exposed to such biocides. Benzalkonium chloride (BAC or BKC) is a non-toxic substance used to control pests. Recently, BAC has been increasingly used as a component in humidifier disinfectants in Korea, raising a serious health concern. Moreover, it poses significant health hazards to workers handling the chemical because of direct exposure. In the present study, we aimed to evaluate the respiratory toxicity of BAC due to its inhalation at exposure concentrations of 0.8 (T1 group), 4 (T2 group) and 20 (T3 group) mg/m3.

Results
In our previous study on the acute inhalational toxicity of BAC, bleeding from the nasal cavity was observed in all the rats after exposure to 50 mg/m3 BAC. Therefore, in this study, 20 mg/m3 was set as the highest exposure concentration, followed by 4 and 0.8 mg/m3 as the medium and low concentrations for 6 h/day and 14 days, respectively. After exposure, recovery periods of 2 and 4 weeks were provided. Additionally, alveolar lavage fluid was analyzed in males of the BAC-exposed groups at the end of exposure and 2 weeks after exposure to evaluate oxidative damage.
In the T3 group exposed to BAC, deep breathing, hoarseness, and nasal discharge were observed along with a decline in feed intake and body weight, and nasal discharge was also observed in the T1 and T2 groups. ROS/RNS, IL-1β, IL-6, and MIP-2 levels decreased in a concentration-dependent manner in the bronchoalveolar lavage fluid. Histopathological examination showed cellular changes in the nasal cavity and the lungs of the TI, T2, and T3 groups.

Conclusions
As a result, it was confirmed that the target organs in the respiratory system were the nasal cavity and the lungs. The adverse effects were evaluated as reversible responses to oxidative damage. Furthermore, the no observed adverse effect level was found to be less than 0.8 mg/m3 and the lowest benchmark dose was 0.0031 mg/m3. Accordingly, the derived no-effect level of BAC was calculated as 0.000062 mg/m3.
Evaluating opportunities for improved orthopedics outpatient satisfaction: an analysis of Press Ganey® Outpatient Medical Practice Survey responses
Authors: Stephens Andrew R. , Rowberry Tyson J. , Tyser Andrew R. , Kazmers Nikolas H. 
Published: January 2020

AbstractIntroductionThe Press Ganey® Outpatient Medical Practice Survey (PGOMPS) is composed of 10 provider-specific and 15 non-provider-specific questions. Some healthcare systems link PGOMS overall scores to physician reimbursements. The aim of this study was to determine the frequency of patient satisfaction across individual PGOMPS question, the null hypothesis being that there was no variability between the frequency of satisfaction and similar questions.MethodsWe reviewed all new patient orthopedic PGOMPS scores between January 2014 and December 2017. Due to the large ceiling effect, satisfaction was defined as a perfect total score. The frequency of perfect scores for each question was calculated.ResultsFive thousand one hundred sixty-three patients met the inclusion criteria. Two thousand two hundred sixty-six (43.89%) provider-specific questions received perfect satisfaction versus 986 (19.10%) with perfect satisfaction for non-provider-specific questions (p <  0.001). The five questions most likely to receive perfect satisfaction were MD friendliness/courtesy (80.36), MD spoke using clear language (80.35%), likelihood to recommend practice (79.11%), likelihood to recommend MD (78.8%), and MD confidence (78.74%). The five least likely were convenience of office hours (60.44%), ease of getting on phone (59.72%), ability to get desired appointment (59.50%), wait time (54.63%), and information about delays (53.80%).ConclusionsOur results suggest that the majority of orthopedic patients are satisfied with their provider, demonstrating that room for improvement is limited with provider-specific areas. Leaders of health care teams should consider these results when seeking to improve patient satisfaction scores and determining how and if scores should be linked to reimbursements.