bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiplex nucleotide editing by high-fidelity Cas9 variants with improved efficiency in rice
Authors: Xu Wen , Song Wei , Yang Yongxing , Wu Ying , Lv Xinxin , Yuan Shuang , Liu Ya , Yang Jinxiao 
Published: November 2019

Abstract
Background
Application of the CRISPR/Cas9 system or its derived base editors enables targeted genome modification, thereby providing a programmable tool to exploit gene functions and to improve crop traits.

Results
We report that PmCDA1 is much more efficient than rAPOBEC1 when fused to CRISPR/Cas9 nickase for the conversion of cytosine (C) to thymine (T) in rice. Three high-fidelity SpCas9 variants, eSpCas9(1.1), SpCas9-HF2 and HypaCas9, were engineered to serve with PmCDA1 (pBEs) as C-to-T base editors. These three high-fidelity editors had distinct multiplex-genome editing efficiencies. To substantially improve their base-editing efficiencies, a tandemly arrayed tRNA-modified single guide RNA (sgRNA) architecture was applied. The efficiency of eSpCas9(1.1)-pBE was enhanced up to 25.5-fold with an acceptable off-target effect. Moreover, two- to five-fold improvement was observed for knock-out mutation frequency by these high-fidelity Cas9s under the direction of the tRNA-modified sgRNA architecture.

Conclusions
We have engineered a diverse toolkit for efficient and precise genome engineering in rice, thus making genome editing for plant research and crop improvement more flexible.
Does depressed persons with non-cardiovascular morbidity have a higher risk of CVD? A population-based cohort study in Sweden
Authors: Almas Aysha , Moller Jette , Iqbal Romaina , Lundin Andreas , Forsell Yvonne 
Published: November 2019

Abstract
Background
Depression often co-exists with non-cardiovascular morbid conditions. Whether this comorbidity increases the risk of cardiovascular disease has so far not been studied. Thus, the aim of this study was to determine if non-cardiovascular morbidity modifies the effect of depression on future risk of CVD.

Methods
Data was derived from the PART study (acronym in Swedish for: Psykisk hälsa, Arbete och RelaTioner: Mental Health, Work and Relationships), a longitudinal cohort study on mental health, work and relations, including 10,443 adults (aged 20–64 years). Depression was assessed using the Major Depression Inventory (MDI) and self-reported data on non-cardiovascular morbidity was assessed in 1998–2000. Outcomes of CVD were assessed using the National Patient Register during 2001–2014.

Results
Both depression (HR 1.5 (95% CI, 1.1, 2.0)) and non-cardiovascular morbidity (HR 2.0 (95% CI, 1.8, 2.6)) were associated with an increased future risk of CVD. The combined effect of depression and non-cardiovascular comorbidity on future CVD was HR 2.1 (95%, CI 1.3, 3.4) after adjusting for age, gender and socioeconomic position. Rather similar associations were seen after further adjustment for hypertension, diabetes and unhealthy lifestyle factors.

Conclusion
Persons affected by depression in combination with non-cardiovascular morbidity had a higher risk of CVD compared to those without non-cardiovascular morbidity or depression alone.
Changes in primary care provider utilization by phase of care for women diagnosed with breast cancer: a CanIMPACT longitudinal cohort study
Authors:   for the Canadian Team to Improve Community-Based Cancer Care Along the Continuum (CanIMPACT), Decker K. , Moineddin R. , Kendell C. , Urquhart R. , Biswanger N. , Groome P. , McBride M. L. , Winget M. , Whitehead M. , Grunfeld E. 
Published: November 2019

Abstract
Background
Primary care providers (PCPs) have always played an important role in cancer diagnosis. There is increasing awareness of the importance of their role during treatment and survivorship. We examined changes in PCP utilization from pre-diagnosis to survival for women diagnosed with breast cancer, factors associated with being a high user of primary care, and variation across four Canadian provinces.

Methods
The cohorts included women 18+ years of age diagnosed with stage I-III invasive breast cancer in years 2007–2012 in British Columbia (BC), Manitoba (MB), Ontario (ON), and Nova Scotia (NS) who had surgery plus adjuvant chemotherapy and were alive 30+ months after diagnosis (N = 19,589). We compared the rate of PCP visits in each province across phases of care (pre-diagnosis, diagnosis, treatment, and survival years 1 to 4).

Results
PCP use was greatest during treatment and decreased with each successive survival year in all provinces. The unadjusted difference in PCP use between treatment and pre-diagnosis was most pronounced in BC where PCP use was six times higher during treatment than pre-diagnosis. Factors associated with being a high user of primary care during treatment included comorbidity and being a high user of care pre-diagnosis in all provinces. These factors were also associated with being a higher user of care during diagnosis and survival.

Conclusions
Contrary to the traditional view that PCPs focus primarily on cancer prevention and early detection, we found that PCPs are involved in the care of women diagnosed with breast cancer across all phases of care.
Elevated serum triglyceride and low-density lipoprotein cholesterol promotes the formation of colorectal polyps
Authors: Xie Chenxi , Wen Pingwu , Su Jingling , Li Qin , Ren Yandan , Liu Yueyu , Shen Renze , Ren Jianlin 
Published: November 2019

Abstract
Background
Hyperlipidaemia may be a potential risk factor for the occurrence of intestinal polyps. This study aimed to evaluate correlation between lipidaemia and the formation of colorectal polyps.

Methods
One hundred and fourteen patients with colorectal polyps and forty-eight healthy controls were included in this study. Colonoscopies were performed for all patients and controls within 1 week before blood samples were taken. The concentrations of serum lipids and lipoproteins were measured simultaneously using an automatic biochemical analyser. The colorectal lesions were classified based on pathological characteristics, and four types were identified in the study: hyperplastic polyp (HP), tubular adenoma (TA), tubulovillous adenoma (TVA) and adenoma with high-grade dysplasia (A-HGD). Advanced adenoma was classified according to the number, size and histological type of polyps.

Results
The value of low-density lipoprotein cholesterol (LDL-C) was significantly higher in the group with advanced adenoma than in the controls (p < 0.05). Moreover, the LDL-C values in the HP and TA groups were higher when compared to that of controls (p < 0.05). Obesity, age, and increased TG and LDL-C were independent risk factors for the formation of colorectal polyps. The cut-off values of triglyceride (TG) and LDL-C to distinguish polyp patients from healthy controls were 0.96 mmol/L (AUC = 0.604, p = 0.036) and 3.05 mmol/L (AUC = 0.654, p = 0.002). The combined use of increased LDL-C and TG levels to distinguish polyp patients was effective, with a sensitivity of 50.0% and a specificity of 89.6% (AUC = 0.733, p < 0.01).

Conclusions
Colorectal polyps are more often found in obese and older patients. Increased LDL-C and TG were correlated with the occurrence of polyps. Combination of the two serum indicators was useful to assess risk of colorectal lesions, maybe more effective in screening hyperplastic polyp, tubular adenoma and advanced adenoma.
Validation of the clinical frailty score (CFS) in French language
Authors: Abraham Paul , Courvoisier Delphine S. , Annweiler Cedric , Lenoir Cliff , Millien Thomas , Dalmaz Francoise , Flaatten Hans , Moreno Rui , Christensen Steffen , de Lange Dylan W. , Guidet Bertrand , Bendjelid Karim , Walder Bernhard , Bollen Pinto Bernardo 
Published: November 2019

AbstractBackgroundVery old critical ill patients are a rapid expanding group. To better understand the magnitude of the challenges involved in intensive care practice for an ageing population and discuss a rational allocation of resources, healthcare practitioners need a reliable evaluation of frailty. In order to promote the adequate use of the Clinical Frailty Scale (CFS) in a wider panel of countries, we aimed to develop, validate and characterise a French (FR) version from the original English (EN) CFS.MethodsWe included participants recruited prospectively for the observational “The very old intensive care patient: A multinational prospective observation study” (VIP Study) at Geneva University Hospitals (FR speaking hospital). A FR version of the CFS was obtained by translation (EN- > FR) and back translation (FR- > EN). The final CFS-FR was then evaluated twice on the same participants with at least a 2-week interval by FR-speaking doctors and nurses.ResultsInter-rater reliability was 0.87 (95%CI: 0.76–0.93) between doctors for the original CFS version and 0.76 (95%CI: 0.57–0.87) between nurses for the FR version. Inter-rater variability between doctor and nurse was 0.75 (95%CI: 0.56–0.87) for the original version, and 0.73 (95%CI: 0.52–0.85) for the FR version.Test-retest (stability) with the original vs the FR version was 0.86 (95%CI: 0.72–0.93) for doctors and 0.87 (95%CI: 0.76–0.93) for nurses.Differences between the evaluations of the CFS-EN and CSF-FR were not different from 0, with a mean difference of 0.06 (95%CI -0.24, 0.36) for the EN version and − 0.03 (95%CI -0.47, 0.41) for the FR version. Average original version ratings were slightly lower than FR version ratings, though this difference did not reach significance: -0.29 (95%CI -0.54, 0.04).ConclusionIn this prospective cohort of very old intensive care participants we developed and tested the basic psychometric properties (internal consistency, reproducibility) of a French version of the CFS. This manuscript provides clinically meaningful psychometric properties that have not been previously reported in any other language, including in the original EN version.The French cultural adaptation of this CFS has adequate psychometric properties for doctors or nurses to evaluate frailty in very old intensive care patients.
Being the next of kin of an older person living in a nursing home: an interview study about quality of life
Authors: Rosén Helena , Behm Lina , Wallerstedt Birgitta , Ahlström Gerd 
Published: November 2019

AbstractBackgroundThe length of stay in nursing homes before death in Sweden has significantly decreased, and nearly one-third of people die within 6 weeks of entering a nursing home. Support for the next of kin is one of the cornerstones of palliative care, but the principles are not always adhered to as recommended when caring for the elderly, which can affect the quality of life of their next of kin. The aim of this study was to explore the experiences of quality of life among the next of kin of older persons who live in nursing homes before an educational intervention of palliative care.MethodsThis is an explorative qualitative interview study with 40 next of kin using qualitative content analysis performed at baseline before the implementation of the principles of palliative care in nursing homes.ResultsThe next of kin’s experiences of quality of life were expressed in three themes: Orientation to the new life situation, Challenges in their relationship and the Significance of the quality of care in the nursing home. The next of kin experienced a sense of relief, although the older person was constantly on their minds, and they could feel lonely. The difference in the couple’slife situations was experienced as burdensome by the next of kin. The challenges in the relationship were described as stressful, related to a guilty conscience and the older person’s vulnerability. The nursing home could be a context facilitating good relations. The perceptions of quality of care in terms of person-centredness affected the quality of life of the next of kin.ConclusionsThe findings show that four factors are decisive for the quality of life of next of kin: the relationships within the family, the degree of relief that nursing home care entails as compared to home care, the older person’s health status and whether the care is person-centred. Increased knowledge and education regarding palliative care in nursing homes are needed to better meet the needs of next of kin. Implementation of palliative care should take into account the need for support for next of kin.Trial registrationNCT02708498, 15 March 2016.
Disability incidence and functional decline among older adults with major chronic diseases
Authors: Fong Joelle H. 
Published: November 2019

AbstractBackgroundMore than 80% of elderly Americans have at least one chronic disease. While past studies have shown that hierarchical patterns of functional loss may differ by gender and institutional settings, little is known about whether such patterns differ in relation to chronic health condition. The aim of this study is to investigate the pattern of functional loss among older adults with major chronic illnesses, and to compare their onset and ordering of incident ADL disability with those of persons without such conditions.MethodsWe use a nationally representative sample of persons aged 80+ from the 1998–2014 Asset and Health Dynamics of the Oldest Old survey. The group with major noncommunicable diseases (including cardiovascular disease, cancer, chronic respiratory disease, and diabetes) comprises 3,514,052 subjects, while the comparison group comprises 1,073,263 subjects. Self-reports of having difficulty with six distinct ADLs are used to estimate disability incidence rate. Nonparametric statistical methods are used to derive median onset ages and ADL loss sequence separately for each group.ResultsOlder adults with major chronic diseases have higher rates of incident disability across all ADL items. Estimated median onset ages of ADL disabilities for the full sample range from 91.5 to 95.6. Disability occurs earlier for chronically ill persons (onset ages 91.1–95.0) than for those in the comparison group (onset ages 93.5–98.1). Among those with major chronic diseases, the ADL loss sequence ordered by median ages of disability onset is bathing, walking, dressing, toileting, transferring and eating. The activities are also distinctly separated into an early-loss cluster and a late-loss cluster. Although the loss sequence derived for the comparison group is largely similar, disability progression for those with major chronic diseases is compressed within a shorter timeframe and the timing gaps between adjacent disabilities are smaller.ConclusionsOlder Americans with major noncommunicable diseases face an earlier and steeper slope of functional decline. Chronic care delivery programs should adapt to dynamic changes in older patients’ functional status. Health interventions to help patients delay disability onset and optimize functional autonomy within emerging models of chronic care should especially target early-loss activities such as bathing, dressing, and walking.
Magnitude of Rotavirus A and Campylobacter jejuni infections in children with diarrhea in Twin cities of Rawalpindi and Islamabad, Pakistan
Authors: Sadiq Asma , Bokhari Habib , Noreen Zobia , Asghar Rai Muhammad , Bostan Nazish 
Published: November 2019

Abstract
Background
Acute diarrhea is a leading cause of morbidity and mortality in children particularly in developing countries of Asia and Africa. The present study was conducted to detect the two most important pathogens, rotavirus and Campylobacter Jejuni in children suffering with diarrhea in Rawalpindi and Islamabad, Pakistan in 2014. The clinical and epidemiological aspects of the disease were also investigated.

Methods
A total of 500 stool samples were collected from children presented with clinical signs and symptoms of acute diarrhea. The samples were initially screened for the presence of rotavirus A (RVA) via ELISA (Enzyme-linked immunosorbent assay) and RT-PCR (Reverse Transcriptase PCR) and then were analysed for C. jejuni by using species specific PCR assay.

Results
The detection rate of RVA was 26.4% (132/500) while, Campylobacter was detected in 52% (260/500) of samples with C. jejuni accounted for 48.2% (241/500) of all study cases. Co-infection of C. jejuni with RVA was identified in 21.8% of all cases. Children with RVA and C. jejuni co-infection showed a higher probability (p = 0.01) to be dehydrated. A significant association (p = 0.02) was found between C. jejuni positive status and fever in children. The median age of children with both RVA and C. jejuni infection was 6–11 months. The RVA detection rate was high in winter months of the year while, C. jejuni infections were documented high in summer over 1 year study period.

Conclusions
The overall results have demonstrated the high prevalence of C. jejuni in Rawalpindi, Islamabad, Pakistan in 2014. The results of present study will not only help to calculate disease burden caused by C. jejuni and rotavirus but also will provide critical information to health authorities in planning public health care strategies against these pathogens.
Assessment of a health facility based active case finding system for Ebola virus disease in Mbandaka, Democratic Republic of the Congo, June–July 2018
Authors: Kunkel Amber , Keita Mory , Diallo Boubacar , le Polain de Waroux Olivier , Subissi Lorenzo , Wague Bocar , Molala Roger , Lonfandjo Pierre , Bokete Sébastien Bokoo , Perea William , Djingarey Mamoudou Harouna 
Published: November 2019

Abstract
Background
The ninth outbreak of Ebola Virus Disease (EVD) in the Democratic Republic of the Congo occurred in Équateur Province from 8 May-24 July 2018. A system of health facility (HF)-based active case finding (ACF) was implemented in Mbandaka, a regional capital with four confirmed EVD cases, following completion of contact tracing. The goal of this HF-based ACF system was to look for undetected EVD cases among patients that visited HFs beginning one week prior to the system’s implementation.

Methods
From 23 June – 24 July 2018, ACF teams visited HFs in Mbandaka and reviewed all medical records as far back as 17 June for any consultations meeting the suspected EVD case definition. The teams then assessed whether to validate these as suspected EVD cases based on factors such as recovery, epidemiological links, and their clinical judgement. ACF teams also assessed HFs’ awareness of EVD symptoms and the process for alerting suspected cases. We calculated descriptive statistics regarding the characteristics of reviewed consultations, alert cases, and visited HFs. We also used univariate and multivariate random effects logistic regression models to evaluate the impact of repeated ACF visits to the same HF on the staff’s awareness of EVD.

Results
ACF teams reviewed 37,746 consultations, of which 690 met the definition of a suspected case of EVD. Two were validated as suspected EVD cases and transferred to the Ebola Treatment Unit for testing; both tested negative. Repeated ACF visits to the same HF were significantly associated with improved EVD awareness (p < 0.001) in univariate and multivariate analyses.

Conclusion
HF-based ACF during EVD outbreaks may improve EVD awareness and reveal many individuals meeting the suspected case definition. However, many who meet this definition may not have EVD, depending on the population size covered by ACF and amount of ongoing EVD transmission. Given the burdensome procedure of testing suspected EVD cases, future HF-based ACF systems would benefit from improved clarity on which patients require further testing.
Intra-abdominal infections: the role of different classifications on the selection of the best antibiotic treatment
Authors: Silva-Nunes João , Cardoso Teresa 
Published: November 2019

Abstract
Background
Intra-abdominal infections (IAIs) represent a most frequent gastrointestinal emergency and serious cause of morbimortality. A full classification, including all facets of IAIs, does not exist. Two classifications are used to subdivide IAIs: uncomplicated or complicated, considering infection extent; and community-acquired, healthcare-associated or hospital-acquired, regarding the place of acquisition. Adequacy of initial empirical antibiotic therapy prescribed is an essential need. Inadequate antibiotic therapy is associated with treatment failure and increased mortality. This study was designed to determine accuracy of different classifications of IAIs to identify infections by pathogens sensitive to current treatment guidelines helping the selection of the best antibiotic therapy.

Methods
A retrospective cohort study including all adult patients discharged from hospital with a diagnosis of IAI between 1st of January and 31st of October, 2016. All variables potentially associated with pre-defined outcomes: infection by a pathogen sensitive to non-pseudomonal cephalosporin or ciprofloxacin plus metronidazole (ATB 1, primary outcome), sensitive to piperacillin-tazobactam (ATB 2) and hospital mortality (secondary outcomes) were studied through logistic regression. Accuracy of the models was assessed by area under receiver operating characteristics (AUROC) curve and calibration was tested using the Hosmer-Lemeshow goodness-of-fit test.

Results
Of 1804 patients screened 154 met inclusion criteria. Sensitivity to ATB 1 was independently associated with male gender (adjusted OR = 2.612) and previous invasive procedures in the last year (adjusted OR = 0.424) (AUROC curve = 0,65). Sensitivity to ATB 2 was independently associated with liver disease (adjusted OR = 3.580) and post-operative infections (adjusted OR = 2.944) (AUROC curve = 0.604). Hospital mortality was independently associated with age ≥ 70 (adjusted OR = 4.677), solid tumour (adjusted OR = 3.127) and sensitivity to non-pseudomonal cephalosporin or ciprofloxacin plus metronidazole (adjusted OR = 0.368).
The accuracy of pre-existing classifications to identify infection by a pathogen sensitive to ATB 1 was 0.59 considering place of acquisition, 0.61 infection extent and 0.57 local of infection, for ATB 2 it was 0.66, 0.50 and 0.57, respectively.

Conclusion
None of existing classifications had a good discriminating power to identify IAIs caused by pathogens sensitive to current antibiotic treatment recommendations. A new classification, including patients’ individual characteristics like those included in the current model, might have a higher potential to distinguish IAIs by resistant pathogens allowing a better choice of empiric antibiotic therapy.