bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of the impact of the Accelerate Pheno™ system on time to result for differing antimicrobial stewardship intervention models in patients with gram-negative bloodstream infections
Authors: Elliott Gerald , Malczynski Michael , Barr Viktorjia O. , Aljefri Doaa , Martin David , Sutton Sarah , Zembower Teresa R. , Postelnick Michael , Qi Chao 
Published: November 2019

Abstract

Background
Initiating early effective antimicrobial therapy is the most important intervention demonstrated to decrease mortality in patients with gram-negative bacteremia with sepsis. Rapid MIC-based susceptibility results make it possible to optimize antimicrobial use through both escalation and de-escalation.

Method
We prospectively evaluated the performance of the Accelerate Pheno™ system (AXDX) for identification and susceptibility testing of gram-negative species and compared the time to result between AXDX and routine standard of care (SOC) using 82 patient samples and 18 challenge organisms with various confirmed resistance mechanisms. The potential impact of AXDX on time to antimicrobial optimization was investigated with various simulated antimicrobial stewardship (ASTEW) intervention models.

Results
The overall positive and negative percent agreement of AXDX for identification were 100 and 99.9%, respectively. Compared to VITEK® 2, the overall essential agreement was 96.1% and categorical agreement was 95.4%. No very major or major errors were detected. AXDX reduced the time to identification by an average of 11.8 h and time to susceptibility by an average of 36.7 h. In 27 patients evaluated for potential clinical impact of AXDX on antimicrobial optimization, 18 (67%) patients could potentially have had therapy optimized sooner with an average of 18.1 h reduction in time to optimal therapy.

Conclusion
Utilization of AXDX coupled with simulated ASTEW intervention notification substantially shortened the time to potential antimicrobial optimization in this cohort of patients with gram-negative bacteremia. This improvement in time occurred when ASTEW support was limited to an 8-h coverage model.
Primary solid lung cancerous nodules with different sizes: computed tomography features and their variations
Authors: Chu Zhi-gang , Zhang Yan , Li Wang-jia , Li Qi , Zheng Yi-neng , Lv Fa-jin 
Published: November 2019

Abstract

Background
The computed tomography (CT) features of small solid lung cancers and their changing regularity as they grow have not been well studied. The purpose of this study was to analyze the CT features of solid lung cancerous nodules (SLCNs) with different sizes and their variations.

Methods
Between February 2013 and April 2018, a consecutive cohort of 224 patients (225 nodules) with confirmed primary SLCNs was enrolled. The nodules were divided into four groups based on tumor diameter (A: diameter ≤ 1.0 cm, 35 lesions; B: 1.0 cm < diameter ≤ 1.5 cm, 60 lesions; C: 1.5 cm < diameter ≤ 2.0 cm, 63 lesions; and D: 2.0 cm < diameter ≤ 3.0 cm, 67 lesions). CT features of nodules within each group were summarized and compared.

Results
Most nodules in different groups were located in upper lobes (groups A − D:50.8%–73.1%) and had a gap from the pleura (groups A − D:89.6%–100%). The main CT features of smaller (diameter ≤ 1 cm) and larger (diameter > 1 cm) nodules were significantly different. As nodule diameter increased, more lesions showed a regular shape, homogeneous density, clear but coarse tumor–lung interface, lobulation, spiculation, spinous protuberance, vascular convergence, pleural retraction, bronchial truncation, and beam-shaped opacity (p < 0.05 for all). The presence of halo sign in all groups was similar (17.5%–22.5%; p > 0.05).

Conclusions
The CT features vary among SLCNs with different sizes. Understanding their changing regularity is helpful for identifying smaller suspicious malignant nodules and early determining their nature in follow-up.
Prevalence of self-stigma and its association with self-esteem among psychiatric patients in a Nepalese teaching hospital: a cross-sectional study
Authors: Maharjan Shanta , Panthee Bimala 
Published: November 2019

Abstract

Background
Stigma against mental illness cuts across all age, religion, ethnic origin or socio-economic status. Similarly, self-stigma among psychiatric patients is also prevalent worldwide. The consequences of self-stigma are low self-esteem, increased severity of symptoms, low treatment adherence, increased rate of suicidality and decreased quality of life. Thus, this study aims to find the prevalence of self-stigma and its association with self-esteem of patients with mental illness in Nepal.

Methods
This was a cross-sectional study conducted among 180 patients with mental illness attending a psychiatric Outpatient Department (OPD). Non-probability purposive sampling technique was used for the study. The data was collected by face to face interview technique. Structured interview schedule questionnaire (brief version of internalized stigma scale and Rosenberg self-esteem scale) was used to collect the data. Descriptive statistics, inferential statistics and correlation analysis were used for data analysis. P value was set at 0.05.

Results
Overall prevalence of self-stigma was 54.44%. Among those who had self-stigma 48% had mild self-stigma, 34.7% had moderate self-stigma and 17.3% had severe self-stigma. Among the five components of self-stigma scale, the highest mean score was on stereotype endorsement, followed by discrimination experience, social withdrawal, stigma resistance, and the lowest for the component of alienation. Furthermore, strong negative correlation (r = − 0.74) was found between self-stigma and self-esteem. The correlation was still significant (r = − 0.69) after controlling for socio-demographic and clinical variables. Hospital admission and diagnostic category of respondents were significantly associated with self-stigma. However, no significant association was found between socio-demographic variables and self-stigma.

Conclusion
Based on the findings of this study, it can be concluded that self-stigma is prevalent among psychiatric patients in Nepal. Most of the respondents experienced stereotype endorsement. Also, higher self-stigma is significantly associated with poor self-esteem suggesting self-stigma reduction programs. Furthermore, strong negative relationship between self-stigma and self-esteem suggests some causal relationship studies to confirm if self-esteem enhancement program can be beneficial to reduce self-stigma among psychiatric patients.
Using epidemiological data to identify needs for child-rearing support among Chinese parents: a cross-sectional survey of parents of children aged 6 to 35 months in 15 Chinese cities
Authors: Zhang Yue , Sanders Matthew , Feng Weiwei , Tang He , Wang Huishan , Jin Xi , Wu Jieling , Huang Guangwen , Sun Jin , Luo Yan , Lv Lanqiu , Yan Shuangqin , Zhao Dongmei , Mu Lijuan , Yan Dongmei , Wang Hong , Gao Xueting , Yang Jing , Wang Hong , Wang Nianrong , Shao Jie , Yang Jinliuxing , Haslam Divna 
Published: November 2019

AbstractBackgroundThe quality of the family environment—in particular, the kind of parenting children receive in their early years—plays a critical role in influencing children’s growth and development. To facilitate the development and delivery of appropriate parenting and family interventions for Chinese parents, this study explores the prevalence of the difficulties that may arise in the course of child-rearing, the associated sociodemographic factors and parents’ help-seeking behavior.MethodsA cross-sectional self-reporting survey was conducted with a sample of 2229 parents of children between 6 and 35 months of age. Using a stratified random-digit design, parents from 15 Chinese cities were surveyed to determine their child-rearing difficulties, support-seeking behavior and their preferences for service delivery. The sociodemographic factors that influenced major child-rearing difficulties were analyzed using bivariate and logistic analyses.ResultsThe majority (87.5%) of Chinese parents of children aged 6–35 months reported experiencing child-rearing difficulties. Nearly one third (31.5%) of parents reported experiencing major difficulties. Feeding and sleep problems were most often reported. Regression analysis revealed that major child-rearing difficulties most often involved male children (OR = 1.35, 95% CI 1.11–1.64), single-child households (OR = 1.38, 95% CI 1.07–1.77), and households with financial problems (OR = 1.40, 95% CI 1.06–1.85). Just over one third of parents (33.44%) sought professional support, while 21.37% had attended a parenting course in the past year. Prefer ways of sourcing parental support included professional online platform (69.24%), self-help books (43.70%), face-to-face consultation (24.99%), and attending lectures (36.57%).ConclusionsChild-rearing difficulties are common among parents of children between 6 and 35 months of age in Chinese cities. The family with boys, single-child, financial problems, and father not joining in child-rearing may face the high risk to major child-rearing difficulties. The national initiative to provide more guidance and support for child-rearing difficulties is worthwhile, as is the development of online parenting programs.
Effective public-private partnerships for sustainable antiretroviral therapy: outcomes of the Right to Care health services GP down-referral program
Authors: Mokhele Idah , Mashamaite Sello , Majuba Pappie , Xulu Thembi , Long Lawrence , Onoya Dorina 
Published: November 2019

Abstract

Background
The recently increased access to antiretroviral therapy (ART) in South Africa has placed additional strain on human and infrastructure resources of the public health sector. Capacity from private-sector General Practitioners (GPs) could be leveraged to ease the current burden on the public health sector.

Methods
We conducted a retrospective record review of routine electronic medical record data on a systematic sample of HIV-infected adults (≥18 years old) initiated on ART at a tertiary hospital outpatient HIV clinic in Johannesburg, South Africa and down-referred to private-GPs for continued care after stabilization on ART. We compared these patients (“GP down-referred”) to a control-cohort who remained at the referring site (“Clinic A”) and patients from a regional hospital outpatient HIV clinic not offering down-referral to GPs (“Clinic B”). Study outcomes assessed are viral load suppression (VL < 50 copies/ml) and attrition from care (all-cause-mortality or > 90-days late for a last-scheduled visit) by 12 months of follow-up following down-referral or eligibility.

Results
A total of 3685 patients, comprising 373 (10.1%) GP down-referred, 2599 (70.5%) clinic A controls, and 713 (19.4%) clinic B controls were included in the analysis. Overall, 1535 patients (53.3%) had a suppressed viral load. A higher portion of GP down-referred patients had a suppressed viral load compared to clinic A and B patients (65.7% vs 49.1% vs 58.9%). After adjusting for demographic and baseline clinical covariates, we found no difference in viral load suppression between GP down-referred and control patients (adjusted relative risk [aRR] for clinic A vs GP down-referred 1.0; 95% CI: 0.9–1.1), (aRR for clinic B vs GP down-referred 1.0; 95% CI: 0.9–1.2).
Clinic B controls experienced the highest attrition compared to GP down-referred and clinic A controls (33.2% vs 11.3% vs 5.9%) and had a higher risk of attrition compared to GP down-referred patients (adjusted hazard ratio [aHR] 4.2; 95% CI: 2.8–6.5), whereas clinic B controls had a lower risk of attrition (aHR 0.5; 95% CI: 0.3–0.7).

Conclusions and recommendations
Our results show that private-GPs can contribute to caring for stabilized public sector HIV patients on life-long ART. However, they require special efforts to improve retention in care.
Effects of pain neuroscience education in hospitalized patients with high tibial osteotomy: a quasi-experimental study using propensity score matching
Authors: Deguchi Naoki , Hirakawa Yoshiyuki , Izawa Shota , Yokoyama Kazuhito , Muraki Keito , Oshibuti Ryouiti , Higaki Yasuki 
Published: November 2019

Abstract

Background
Pain neuroscience education (PNE) has been shown to reduce pain or psychological symptoms in patients with chronic pain and preoperative knee osteoarthritis; however, the evidence of its effectiveness in hospitalized patients who have undergone high tibial osteotomy (HTO) is unknown. This study was performed to determine whether the implementation of a newly developed hospital-time PNE provided by physical therapists to patients after HTO can result in meaningful improvements.

Methods
In total, 119 patients aged ≥45 years with knee osteoarthritis who were scheduled to undergo HTO were analyzed. Patients with a low Pain Catastrophizing Scale (PCS) score of < 21 were excluded. The patients were classified into two groups: those who underwent a combination of PNE and rehabilitation (intervention group, n = 67) and those who underwent rehabilitation only (control group, n = 52). The patients were pseudo-randomized by their baseline demographic factors using a propensity score-matching method. The PNE was based on a psychosocial model and began 1 week postoperatively in a group setting; five 1-h weekly sessions were conducted. The primary outcome was the walking pain score as measured by a numerical rating scale. The secondary outcomes were the pain catastrophizing scores as measured by the PCS, self-efficacy as measured by the Pain Self-Efficacy Questionnaire, and physical function. Measurements were taken at baseline (before surgery) and before discharge from the hospital (5 weeks postoperatively) to identify any intervention effects.

Results
After propensity score matching, 52 pairs of patients were extracted. In the intervention group, 46 (88.5%) patients completed the PNE. In total, 44 patients in the intervention group and 52 patients in the control group were analyzed. Five weeks following surgery, the rehabilitation itself had also significantly decreased catastrophizing, and the difference between the two groups had only a small effect size (d = 0.44).

Conclusions
These findings provide preliminary evidence that physical therapist-delivered PNE during hospitalization may help to at least slightly reduce pain catastrophizing in patients with catastrophizing prior to knee arthroplasty.

Trial registration
This trial was retrospectively registered with ClinicalTrials.gov (UMIN000037114) on 19 June 2019.
Preimplantation genetic testing for a family with usher syndrome through targeted sequencing and haplotype analysis
Authors: Luo Haining , Chen Chao , Yang Yun , Zhang Yinfeng , Yuan Yuan , Wang Wanyang , Wu Renhua , Peng Zhiyu , Han Ying , Jiang Lu , Yao Ruqiang , An Xiaoying , Zhang Weiwei , Le Yanqun , Xiang Jiale , Yi Na , Huang Hui , Li Wei , Zhang Yunshan , Sun Jun 
Published: November 2019

Abstract

Background
Preimplantation genetic testing for monogenic defects (PGT-M) has been available in clinical practice. This study aimed to validate the applicability of targeted capture sequencing in developing personalized PGT-M assay.

Methods
One couple at risk of transmitting Usher Syndrome to their offspring was recruited to this study. Customized capture probe targeted at USH2A gene and 350 kb flanking region were designed for PGT-M. Eleven blastocysts were biopsied and amplified by using multiple displacement amplification (MDA) and capture sequencing. A hidden Markov model (HMM) assisted haplotype analysis was performed to deduce embryo’s genotype by using single nucleotide polymorphisms (SNPs) identified in each sample. The embryo without paternal rare variant was implanted and validated by conventional prenatal or postnatal diagnostic means.

Results
Four embryos were diagnosed as free of father’s rare variant, two were transferred and one achieved a successful pregnancy. The fetal genotype was confirmed by Sanger sequencing of fetal genomic DNA obtained by amniocentesis. The PGT-M and prenatal diagnosis results were further confirmed by the molecular diagnosis of the baby’s genomic DNA sample. The auditory test showed that the hearing was normal.

Conclusions
Targeted capture sequencing is an effective and convenient strategy to develop customized PGT-M assay.
CDK5RAP3 inhibits angiogenesis in gastric neuroendocrine carcinoma by modulating AKT/HIF-1α/VEGFA signaling
Authors: Lin Jian-Xian , Weng Xiong-Feng , Xie Xin-Sheng , Lian Ning-Zi , Qiu Sheng-Liang , Wang Jia-Bin , Lu Jun , Chen Qi-Yue , Cao Long-Long , Lin Mi , Tu Ru-Hong , Yang Ying-Hong , Liu Si-Jia , Hu Min , Lin Yi-Ke , Huang Chang-Ming , Zheng Chao-Hui , Li Ping , Xie Jian-Wei 
Published: November 2019

Abstract

Background
Angiogenesis plays critical roles in the progression and metastasis of malignant tumors. Gastric neuroendocrine carcinoma is an uncommon stomach cancer that is rich in blood vessels and exhibits highly malignant biological behavior with a poor prognosis. The role of CDK5RAP3 in GNEC has not been reported to date.

Methods
Immunohistochemistry was used to assess the expression of CDK5RAP3 in GNEC tissues and adjacent non-tumor tissues. Cell lines with stable overexpression or knockdown of CDK5RAP3 were constructed using lentiviral transfection. Wound-healing assays, invasion and metastasis assays, tube formation assays, and tumor xenograft transplantation assays were performed to evaluate the effect of CDK5RAP3 on GNEC angiogenesis in vitro and in vivo. Real-time PCR, ELISA, western blot analysis, and confocal-immunofluorescence staining were used to explore the molecular mechanism of CDK5RAP3′s effect on angiogenesis.

Results
Compared with their respective adjacent non-tumor tissues, protein levels of CDK5RAP3 were significantly decreased in GNEC tissues. Furthermore, low expression of CDK5RAP3 was correlated with more advanced TNM stage, increased tumor microvessel density, and poor prognosis. Functionally, we found that GNEC cells with CDK5RAP3 knockdown promoted human umbilical vein endothelial cells migration and tube formation via activation of AKT/HIF-1α/VEGFA signaling, resulting in increased levels of VEGFA in GNEC cell supernatant. In addition, CDK5RAP3 overexpression in GNEC cells caused the opposing effect. Consistent with these results, nude mouse tumorigenicity assays showed that CDK5RAP3 expression downregulated angiogenesis in vivo. Lastly, patients with low CDK5RAP3 expression and high VEGFA expression exhibited the worst prognosis.

Conclusions
This study demonstrated that CDK5RAP3 inhibits angiogenesis by downregulating AKT/HIF-1α/VEGFA signaling in GNEC and improves patient prognosis, suggesting that CDK5RAP3 could be a potential therapeutic target for GNEC.
Left ventricular clefts – incidental finding or pathologic sign of Wilson’s disease?
Authors: Zhang Kun , Reuner Ulrike , Weidauer Marie , Speiser Uwe , Ibrahim Karim , Christoph Marian , Heinzel Frank R. , Pieske Burkert , Heidrich Felix M. , Quick Silvio 
Published: November 2019

Abstract

Background
Wilson’s disease is an inherited autosomal recessive multi-systemic disorder characterized by reduced excretion and consequently excessive accumulation of copper in different organs, such as the heart.

Results
In a prospective controlled trial, which is the largest to date, we evaluated 61 patients with Wilson’s disease, age- and sex-matched to 61 healthy patients, for cardiac manifestation using cardiac magnetic resonance imaging. Patients were under stable disease and had no signs of heart failure at the time of examination.
We detected a left ventricular cleft, an invagination penetrating more than 50% wall thickness of the adjoining compact myocardium in diastole, in 20% of the patients (12 out of 61) compared to 5% among control patients (3 out of 61, p = 0.013). No correlation between the incidence of cleft and a certain genotype of Wilson’s disease was found. All described cases were incidental findings and none of the patients showed other signs of cardiac involvement.

Conclusions
To conclude, the results of this study suggests that the increased occurrence of left ventricular clefts is due to Wilson’s disease. Large studies with a long observation period are needed for further evaluation.
Dysregulation of neuron differentiation in an autistic savant with exceptional memory
Authors: Song Jinjing , Yang Xiujuan , Zhou Ying , Chen Lei , Zhang Xu , Liu Zhuxi , Niu Weibo , Zhan Nengpeng , Fan Xuelian , Khan Abdul Aziz , Kuang Yifang , Song Lulu , He Guang , Li Weidong 
Published: November 2019

Abstract
Autism spectrum disorder (ASD) is a heterogeneous group of complex neurodevelopmental disorders without a unique or definite underlying pathogenesis. Although savant syndrome is common in ASD, few models are available for studying the molecular and cellular mechanisms of this syndrome. In this study, we generated urinary induced pluripotent stem cells (UiPSCs) from a 13-year-old male autistic savant with exceptional memory. The UiPSC-derived neurons of the autistic savant exhibited upregulated expression levels of ASD genes/learning difficulty-related genes, namely PAX6, TBR1 and FOXP2, accompanied by hypertrophic neural somas, enlarged spines, reduced spine density, and an increased frequency of spontaneous excitatory postsynaptic currents. Although this study involved only a single patient and a single control because of the rarity of such cases, it provides the first autistic savant UiPSC model that elucidates the potential cellular mechanisms underlying the condition.
Quality of life in chronic conditions using patient-reported measures and biomarkers: a DEA analysis in type 1 diabetes
Authors: Borg Sixten , Gerdtham Ulf-G. , Eeg-Olofsson Katarina , Palaszewski Bo , Gudbjörnsdottir Soffia 
Published: November 2019

AbstractBackgroundA chronic disease impacts a patient’s daily life, with the burden of symptoms and managing the condition, and concerns of progression and disease complications. Such aspects are captured by Patient-Reported Outcomes Measures (PROM), assessments of e.g. wellbeing. Patient-Reported Experience Measures (PREM) assess patients’ experiences of healthcare and address patient preferences. Biomarkers are useful for monitoring disease activity and treatment effect and determining risks of progression and complications, and they provide information on current and future health. Individuals may differ in which among these aspects they consider important. We aimed to develop a measure of quality of life using biomarkers, PROM and PREM, that would provide an unambiguous ranking of individuals, without presuming any specific set of importance weights. We anticipated it would be useful for studying needs and room for improvement, estimating the effects of interventions and comparing alternatives, and for developing healthcare with a broad focus on the individual. We wished to examine if efficiency analysis could be used for this purpose, in an application to individuals with type 1 diabetes.ResultsWe used PROM and PREM data linked to registry data on risk factors, in a large sample selected from the National Diabetes Registry in Sweden. Efficiency analysis appears useful for evaluating the situation of individuals with type 1 diabetes. Quality of life was estimated as efficiency, which differed by age. The contribution of different components to quality of life was heterogeneous, and differed by gender, age and duration of diabetes. Observed quality of life shortfall was mainly due to inefficiency, and to some extent due to the level of available inputs.ConclusionsThe efficiency analysis approach can use patient-reported outcomes measures, patient-reported experience measures and comorbidity risk factors to estimate quality of life with a broad focus on the individual, in individuals with type 1 diabetes. The approach enables ranking and comparisons using all these aspects in parallel, and allows each individual to express their own view of which aspects are important to them. The approach can be used for policy regarding interventions on inefficiency as well as healthcare resource allocation, although currently limited to type 1 diabetes.