bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of post-exposure prophylaxis practices to improve the cost-effectiveness of rabies control in human cases potentially exposed to rabies in southern Bhutan
Authors: Penjor Kinley , Marquetoux Nelly , Dorji Chendu , Penjor Kinley , Dorjee Sithar , Dorjee Chencho , Jolly P. D. , Morris R. S. , McKenzie J. S. 
Published: March 2020

Abstract
Background
Rabies is endemic in southern Bhutan, associated with 1–2 human deaths and high post exposure prophylaxis (PEP) costs annually. Evaluation of clinicians’ management of human cases potentially exposed to rabies could contribute to improving PEP prescribing practices to both reduce unnecessary costs associated with PEP and reach the target of zero human deaths due to rabies by 2023.

Methods
A cross-sectional survey of 50 clinicians’ management of human cases potentially exposed to rabies was conducted in 13 health centers in high-rabies-risk areas of Bhutan during February–March 2016.

Results
Data were collected on clinicians’ management of 273 human cases potentially exposed to rabies. The 50 clinicians comprised health assistants or clinical officers (55%) and medical doctors (45%) with a respective median of 19, 21 and 2 years’ experience. There was poor agreement between clinicians’ rabies risk assessment compared with an independent assessment for each case based on criteria in the National Rabies Management Guidelines (NRMG). Of the 194 cases for which clinicians recorded a rabies risk category, only 53% were correctly classified when compared with the NRMG. Clinicians were more likely to underestimate the risk of exposure to rabies and appeared to prescribe PEP independently of their risk classification.. Male health assistants performed the most accurate risk assessments while female health assistants performed the least accurate. Clinicians in Basic Health Units performed less accurate risk assessments compared with those in hospitals.

Conclusions
This study highlights important discrepancies between clinicians’ management of human cases potentially exposed to rabies and recommendations in the NRMG. In particular, clinicians were not accurately assessing rabies risk in potentially exposed cases and were not basing their PEP treatment on the basis of their risk assessment. This has significant implications for achieving the national goal of eliminating dog-mediated human rabies by 2030 and may result in unnecessary costs associated with PEP. Recommendations to improve clinician’s management of human cases potentially exposed to rabies include: reviewing and updating the NRMG, providing clinicians with regular and appropriately targeted training about rabies risk assessment and PEP prescription, and regularly reviewing clinicians’ practices.
Furosemide stress test and interstitial fibrosis in kidney biopsies in chronic kidney disease
Authors: Rivero Jesús , Rodríguez Francisco , Soto Virgilia , Macedo Etienne , Chawla Lakhmir S. , Mehta Ravindra L. , Vaingankar Sucheta , Garimella Pranav S. , Garza Carlos , Madero Magdalena 
Published: March 2020

Abstract
Background
Interstitial fibrosis (IF) on kidney biopsy is one of the most potent risk factors for kidney disease progression. The furosemide stress test (FST) is a validated tool that predicts the severity of acute kidney injury (especially at 2 h) in critically ill patients. Since furosemide is secreted through the kidney tubules, the response to FST represents the tubular secretory capacity. To our knowledge there is no data on the correlation between functional tubular capacity assessed by the FST with IF on kidney biopsies from patients with chronic kidney disease (CKD). The aim of this study was to determine the association between urine output (UO), Furosemide Excreted Mass (FEM) and IF on kidney biopsies after a FST.

Methods
This study included 84 patients who underwent kidney biopsy for clinical indications and a FST. The percentage of fibrosis was determined by morphometry technique and reviewed by a nephropathologist. All patients underwent a FST prior to the biopsy. Urine volume and urinary sodium were measured in addition to urine concentrations of furosemide at different times (2, 4 and 6 h). We used an established equation to determine the FEM. Values were expressed as mean, standard deviation or percentage and Pearson Correlation.

Results
The mean age of the participants was 38 years and 44% were male. The prevalence of diabetes mellitus, hypertension and diuretic use was significantly higher with more advanced degree of fibrosis. Nephrotic syndrome and acute kidney graft dysfunction were the most frequent indications for biopsy. eGFR was inversely related to the degree of fibrosis. Subjects with the highest degree of fibrosis (grade 3) showed a significant lower UO at first hour of the FST when compared to lower degrees of fibrosis (p = 0.015). Likewise, the total UO and the FEM was progressively lower with higher degrees of fibrosis. An inversely linear correlation between FEM and the degree of fibrosis (r = − 0.245, p = 0.02) was observed.

Conclusions
Our findings indicate that interstitial fibrosis correlates with total urine output and FEM. Further studies are needed to determine if UO and FST could be a non-invasive tool to evaluate interstitial fibrosis.

Trial registration
ClinicalTrials.gov NCT02417883.
The association between symptoms of depression during pregnancy and low birth weight: a prospective study
Authors: Li Xiuxiu , Gao Rui , Dai Xiaowei , Liu Hong , Zhang Jinxin , Liu Xuemei , Si Dongmei , Deng Te , Xia Wei 
Published: March 2020

Abstract
Background
Most studies have showed that maternal depression is associated with pregnancy complications. However, there were limited evidences in Chinese population. We examined the associations of antenatal depression symptoms with pregnancy outcomes, especially for low birth weight.

Methods
A total of 1377 singleton pregnant women were recruited from Nanshan Maternity & Child Healthcare Hospital of Shenzhen in this prospective cohort study. Depression symptoms were assessed by the Edinburgh postnatal depression scale (EPDS) questionnaire in the second trimester of gestation; cut-points for the indication of antenatal depression were ≧12 scores in this study. Socio-demographic data, life-style and pregnancy outcomes were collected through Shenzhen Maternity & Child Healthcare database. The risks of adverse outcomes in pregnant women with antenatal depression were determined by multivariate logistic regression and represented as odds ratio(OR) and 95% confidence interval (CI).

Results
Of the 1377 subjects, the prevalence of antenatal depression was 19.1%. The EPDS scores were 13.8 ± 2.0 and 6.5 ± 2.9 (P < 0.001) in subjects with and without antenatal depression, respectively. After adjustment for maternal age, education, parity, pre-pregnancy body mass index (BMI), residential area, fetal gender, an EPDS score ≥ 12 (versus. < 12) was associated with an increased risk for low birth weight (odds ratio: 2.05, 95% CI: 1.12–4.64), but not for preterm birth, large for gestational age, small for gestational age or macrosomia.

Conclusion
Pregnant women presenting antenatal depressive symptoms are at elevated risk of low birth weight. Mental health problems of pregnancy should be addressed for the prevention of low birth weight.
Accuracy of detecting residual disease after neoadjuvant chemoradiotherapy for esophageal squamous cell carcinoma (preSINO trial): a prospective multicenter diagnostic cohort study
Authors: Zhang Xiaobin , Eyck Ben M. , Yang Yang , Liu Jun , Chao Yin-Kai , Hou Ming-Mo , Hung Tsung-Min , Pang Qingsong , Yu Zhen-Tao , Jiang Hongjing , Law Simon , Wong Ian , Lam Ka-On , van der Wilk Berend J. , van der Gaast Ate , Spaander Manon C. W. , Valkema Roelf , Lagarde Sjoerd M. , Wijnhoven Bas P. L. , van Lanschot J. Jan B. , Li Zhigang 
Published: March 2020

Abstract
Background
After neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer, high pathologically complete response (pCR) rates are being achieved especially in patients with squamous cell carcinoma (SCC). An active surveillance strategy has been proposed for SCC patients with clinically complete response (cCR) after nCRT. To justify omitting surgical resection, patients with residual disease should be accurately identified. The aim of this study is to assess the accuracy of response evaluations after nCRT based on the preSANO trial, including positron emission tomography with computed tomography (PET-CT), endoscopy with bite-on-bite biopsies and endoscopic ultrasonography (EUS) with fine-needle aspiration (FNA) in patients with potentially curable esophageal SCC.

Methods
Operable esophageal SCC patients who are planned to undergo nCRT according to the CROSS regimen and are planned to undergo surgery will be recruited from four Asian centers. Four to 6 weeks after completion of nCRT, patients will undergo a first clinical response evaluation (CRE-1) consisting of endoscopy with bite-on-bite biopsies. In patients without histological evidence of residual tumor (i.e. without positive biopsies), surgery will be postponed another 6 weeks. A second clinical response evaluation (CRE-2) will be performed 10–12 weeks after completion of nCRT, consisting of PET-CT, endoscopy with bite-on-bite biopsies and EUS with FNA. Immediately after CRE-2 all patients without evidence of distant metastases will undergo esophagectomy. Results of CRE-1 and CRE-2 as well as results of the three single diagnostic modalities will be correlated to pathological response in the resection specimen (gold standard) for calculation of sensitivity, specificity, negative predictive value and positive predictive value.

Discussion
If the current study shows that major locoregional residual disease (> 10% residual carcinoma or any residual nodal disease) can be accurately (i.e. with sensitivity of 80.5%) detected in patients with esophageal SCC, a prospective trial will be conducted comparing active surveillance with standard esophagectomy in patients with a clinically complete response after nCRT (SINO trial).

Trial registration
The preSINO trial has been registered at ClinicalTrials.gov as NCT03937362 (May 3, 2019).
BMI modified the association of current smoking with the incidence of hypertension in Chinese population: a 22-year cohort study
Authors: Yao Feifei , Liu Wenfeng , Zhao Rencheng , Li Guangxiao , Huang Xiaojuan , Chen Yongjie 
Published: March 2020

AbstractBackgroundThere was little known on how the interaction effect between obesity and current smoking affected the incidence of hypertension. The aim of this study was to investigate how body mass index (BMI) modified the effect of current smoking on the incidence of hypertension.MethodsData were obtained from the China Health and Nutrition Survey (CHNS). According to the WHO recommendations for Chinese people, the normal weight, overweight, and obesity were defined using the BMI cutoff values 18.5 kg/m2, 23.0 kg/m2, and 27.5 kg/m, respectively. Current smokers were defined as having smoked at least 100 cigarettes or electronic cigarettes, 20 cigars, or 20 tobacco pipes and other type of tobacco in the last 30 days preceding the survey. Hypertension was defined as systolic blood pressure (SBP)/ diastolic blood pressure (DBP) ≥ 140/90 mmHg, use of anti-hypertensive medications, or a self-reported diagnosis.ResultsThis study included 12,900 subjects. There were interaction effects between obesity and current smoking in females (P = 0.030) and the 50–59 years group (P = 0.049). Current smoking was a significant predictor of incident hypertension only in the total and female populations with normal weight (HR: 1.119 and 1.274;HR95%CI: 1.013–1.236 and 1.143–1.415; andP = 0.027 and 0.040, respectively). Stratified by age, current smoking affected the development of hypertension only in the 50–59 years subjects with the normal weight (HR: 1.356;HR95%CI: 1.084–1.697; andP = 0.008).ConclusionsCurrent smoking was a significant predictor of incident hypertension only in the female and middle-age populations with normal weight but not in the overweight and obesity as well as the younger and elder populations.
The assessment of spiritual well-being in cancer patients with advanced disease: which are its meaningful dimensions?
Authors: Rabitti Elisa , Cavuto Silvio , Iani Luca , Ottonelli Simona , De Vincenzo Francesco , Costantini Massimo 
Published: March 2020

Abstract
Background
Spirituality is particularly important for patients suffering from life-threatening illness. Despite research showing the benefits of spiritual assessment and care for terminally ill patients, their spiritual needs are rarely addressed in clinical practice. This study examined the factor structure and reliability of the Functional Assessment of Chronic Illness Therapy-Spiritual (FACIT-Sp) in patients with advanced cancer. It also examined the clinical meaning and reference intervals of FACIT-Sp scores in cancer patients subgroups through a literature review.

Methods
A forward-backward translation procedure was adopted to develop the Italian version of the FACIT-Sp, which was administered to 150 terminally ill cancer patients. Exploratory factor analysis was used for construct validity, while Cronbach’s α was used to assess the reliability of the scale.

Results
This study replicates previous findings indicating that the FACIT-Sp distinguish well between features of meaning, peace, and faith. In addition, the internal consistency of the FACIT-Sp was acceptable. The literature review also showed that terminal cancer patients have the lowest scores on the Faith and Meaning subscales, whereas cancer survivors have the highest scores on Faith.

Conclusions
The Italian version of the FACIT-Sp has good construct validity and acceptable reliability. Therefore, it can be used as a tool to assess spiritual well-being in Italian terminally ill cancer patients. This study provides reference intervals of FACIT-Sp scores in newly diagnosed cancer patients, cancer survivors, and terminally ill cancer patients and further highlights the clinical meaning of such detailed assessment.
Underlying goals of advance care planning (ACP): a qualitative analysis of the literature
Authors: Fleuren Nienke , Depla Marja F. I. A. , Janssen Daisy J. A. , Huisman Martijn , Hertogh Cees M. P. M. 
Published: March 2020

Abstract
Background
Since the introduction of the concept of advance care planning (ACP), many studies have been conducted exploring beneficial effects. These studies show a heterogeneity in clinical endpoints, which reflects diversity of goals connected to ACP. This study aims to get insight in the range of underlying goals that comprise the legitimacy of ACP.

Methods
Systematic literature search in PubMed, EMBASE, PsychInfo, CINAHL and Cochrane Library. Articles on normative aspects of ACP were included, based on title and abstract. Due to the quantity of inclusions, of which many had similar content, purposive sampling was used to select articles for full text document analysis. Analysis stopped once saturation was reached.

Results
In total, 6497 unique articles were found of which 183 were included. Saturation was reached after document analysis of 55 articles (30%); this yielded 141 codes concerning goals of ACP and also 70 codes about objections against ACP, which shed light on the underlying goals of ACP as well. We identified five underlying goals: respecting individual patient autonomy, improving quality of care, strengthening relationships, preparing for end-of-life, reducing overtreatment.

Conclusions
Five distinctive underlying goals of ACP were identified, each with corresponding objections that need to be considered. Specifying underlying goals of ACP may direct the debate on definitions, methods and preferred outcomes of ACP.
This study was funded by the Netherlands Organisation for Health Research and Development, grant 839120002.
Hepatoprotective effects of gamma-aminobutyric acid-enriched fermented Hovenia dulcis extract on ethanol-induced liver injury in mice
Authors: Park Na-Hye , Lee Seung-Jin , Mechesso Abraham Fikru , Boby Naila , Yixian Quah , Yoon Woong-Kyu , Lee Sam-Pin , Lee Jong-Suk , Park Seung-Chun 
Published: March 2020

Abstract
Background
Various extracts of Hovenia dulcis have been commonly used in Asia for cases of alcohol-related disorders. Fermentation is reported to enhance the level and biological activities of various bio-constituents of plant extracts. Therefore, this study was undertaken to evaluate the effects of fermented H. dulcis extract (FHDE) on ethanol-induced liver injury in mice.

Methods
FHDE was prepared using Bacillus subtilis and Lactobacillus plantarum. The effects of FHDE on ethanol-induced liver injury were evaluated in C57BL/6 N CrSlc mice. A mixed feed preparation containing the fermented extract with and without ethanol was given to mice for 29 days, according to its group. At the end of the experiment, blood and liver samples were collected from all mice in the group. Plasma biochemical analysis and histopathological investigation were performed to evaluate the impacts of treatment on the biomarkers of hepatic damage and inflammatory changes. Besides, the expression of genes that regulate the activities of enzymes associated with alcohol metabolism, antioxidant activity, and fatty acid oxidation was assessed using a quantitative real-time polymerase chain reaction. Moreover, the amino acid contents and the active ingredients of the extract were evaluated before and after fermentation.

Results
Fermentation resulted in a marked increase and decrease in the amount of Gamma-Amino-n-butyric acid (GABA) and glutamic acid, respectively. FHDE enhanced the body weight gain of mice compared to ethanol. Besides, plasma levels of triglyceride, low-density lipoprotein, the activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were significantly (P < 0.05) reduced in the FHDE-treated groups relative to the ethanol-treated control. FHDE upregulated the expression of genes associated with enzymes involved in alcohol dehydrogenation (Adh1 and Aldh2), antioxidant activity (SOD and CAT), and fatty acid oxidation (PPAR-α and PGC-1α). However, the expressions of Cytochrome peroxidase Cyp2E1 and genes related to lipogenesis (SREBP-1c, FAS, SCD-1, and ACC) were significantly (P < 0.05) downregulated following treatment with the FHDE. Histopathological investigation demonstrated a slight degree of inflammatory cell infiltration and occasional fatty changes in the FHDE-treated groups.

Conclusion
The GABA-enriched fermented H. dulcis extract prevented ethanol-induced hepatic damage by enhancing the antioxidant defense system, fatty acid oxidation, and reducing lipogenesis.
Protection from hydrogen peroxide stress relies mainly on AhpCF and KatA2 in Stenotrophomonas maltophilia
Authors: Li Li-Hua , Shih Yung-Luen , Huang Jing-Yun , Wu Chao-Jung , Huang Yi-Wei , Huang Hsin-Hui , Tsai Yu-Chieh , Yang Tsuey-Ching 
Published: March 2020

Abstract
Background
Aerobically-grown bacteria can be challenged by hydrogen peroxide stress from endogenous aerobic metabolism and exogenously generated reactive oxygen species. Catalase (Kat), alkyl hydroperoxidase (Ahp), and glutathione peroxidase (Gpx) systems are major adaptive responses to H2O2 stress in bacteria. Stenotrophomonas maltophilia is a ubiquitous Gram-negative bacterium equipped with four Kats (KatA1, KatA2, KatMn, and KatE), one Ahp (AhpCF), and three Gpxs (Gpx1, Gpx2, and Gpx3). Here, we systematically investigated how the eight H2O2 scavenging genes differentially contribute to the low-micromolar levels of H2O2 generated from aerobic metabolism and high-millimolar levels of H2O2 from exogenous sources.

Methods
Gene expression was assessed and quantified by reverse transcription-PCR (RT-PCR) and real time quantitative PCR (qRT-PCR), respectively. The contribution of these enzymes to H2O2 stress was assessed using mutant construction and functional investigation.

Results
Of the eight genes, katA2, ahpCF, and gpx3 were intrinsically expressed in response to low-micromolar levels of H2O2 from aerobic metabolism, and the expression of katA2 and ahpCF was regulated by OxyR. AhpCF and KatA2 were responsible for alleviating aerobic growth-mediated low concentration H2O2 stress and AhpCF played a critical role for stationary-phase cells. KatA2 was upregulated to compensate for AhpCF in the case of ahpCF inactivation. After exposure to millimolar levels of H2O2, katA2 and ahpCF were upregulated in an OxyR-dependent manner. KatA2 was the critical enzyme for dealing with high concentration H2O2. Loss-of-function of KatA2 increased bacterial susceptibility to high concentration H2O2.

Conclusions
AhpCF and KatA2 are key enzymes protecting S. maltophilia from hydrogen peroxide stress.
Expression regulation of multiple key genes to improve l-threonine in Escherichia coli
Authors: Zhao Lei , Lu Ying , Yang Jun , Fang Yu , Zhu Lifei , Ding Zhixiang , Wang Chenhui , Ma Wenjian , Hu Xiaoqing , Wang Xiaoyuan 
Published: March 2020

AbstractBackgroundEscherichia coliis an important strain forl-threonine production. Genetic switch is a ubiquitous regulatory tool for gene expression in prokaryotic cells. To sense and regulate intracellular or extracellular chemicals, bacteria evolve a variety of transcription factors. The key enzymes required forl-threonine biosynthesis inE. coliare encoded by thethroperon. Thethroperon could coordinate expression of these genes whenl-threonine is in short supply in the cell.ResultsThethrLleader regulatory elements were applied to regulate the expression of genesiclR,arcA,cpxR,gadE,fadRandpykF, while the threonine-activating promotersPcysH,PcysJandPcysDwere applied to regulate the expression of geneaspC, resulting in the increase ofl-threonine production in anl-threonine producingE. colistrain TWF001. Firstly, different parts of the regulatorthrLwere inserted in theiclRregulator region in TWF001, and the best resulting strain TWF063 produced 16.34 gl-threonine from 40 g glucose after 30 h cultivation. Secondly, the geneaspCfollowing different threonine-activating promoters was inserted into the chromosome of TWF063, and the best resulting strain TWF066 produced 17.56 gl-threonine from 40 g glucose after 30 h cultivation. Thirdly, the effect of expression regulation ofarcA,cpxR,gadE,pykFandfadRwas individually investigated onl-threonine production in TWF001. Finally, using TWF066 as the starting strain, the expression of genesarcA,cpxR,gadE,pykFandfadRwas regulated individually or in combination to obtain the best strain forl-threonine production. The resulting strain TWF083, in which the expression of seven genes (iclR,aspC,arcA,cpxR,gadE,pykF,fadRandaspC) was regulated, produced 18.76 gl-threonine from 30 g glucose, 26.50 gl-threonine from 40 g glucose, or 26.93 gl-threonine from 50 g glucose after 30 h cultivation. In 48 h fed-batch fermentation, TWF083 could produce 116.62 g/Ll‐threonine with a yield of 0.486 g/g glucose and productivity of 2.43 g/L/h.ConclusionThe genetic engineering through the expression regulation of key genes is a better strategy than simple deletion of these genes to improvel-threonine production inE. coli. This strategy has little effect on the intracellular metabolism in the early stage of the growth but could increasel-threonine biosynthesis in the late stage.