bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validity and reliability of the English and translated Chinese versions of the Integrated Palliative care Outcome Scale (IPOS) in Singapore
Authors: Long Victoria Jane En , Cheung Yin Bun , Qu Debra , Lim Katherine , Lee Guozhang , Yee Alethea C. P. , Guo Ping , Harding Richard , Yang Grace Meijuan 
Published: March 2021

Abstract
Context
Measurement of patient-centred outcomes enables clinicians to focus on patient and family priorities and enables quality of palliative care to be assessed.

Objectives
This study aimed to evaluate the validity and reliability of the English and translated Chinese versions of the Integrated Palliative care Outcome Scale (IPOS) among advanced cancer patients in Singapore.

Methods
IPOS was forward and backward translated from English into Chinese. Structural validity was assessed by confirmatory factor analysis; known-group validity by comparing inpatients and community patients; construct validity by correlating IPOS with Edmonton Symptom Assessment System-revised (ESAS-r) and Functional Assessment of Cancer Therapy–General (FACT-G); internal consistency by Cronbach’s alpha; inter-rater reliability between patient and staff responses; test-retest reliability of patient responses between two timepoints.

Results
One hundred eleven English-responding and 109 Chinese-responding patients participated. The three-factor structure (Physical Symptoms, Emotional Symptoms and Communication and Practical Issues) was confirmed with Comparative Fit Index and Tucker-Lewis-Index > 0.9 and Root Mean Square Error of Approximation < 0.08. Inpatients scored higher than outpatients as hypothesised. Construct validity (Pearson’s correlation coefficient, r ≥ |0.608|) was shown between the related subscales of IPOS and FACT-G and ESAS-r. Internal consistency was confirmed for total and subscale scores (Cronbach’s alpha≥0.84), except for the Communication and Practical Issues subscale (Cronbach’s alpha = 0.29–0.65). Inter-rater reliability (Intra-class correlation coefficient [ICC] ≤ 0.43) between patient and staff responses was insufficient. Test-retest reliability was confirmed with Intra-class correlation coefficient ICC = 0.80 (English) and 0.88 (Chinese) for IPOS Total.

Conclusion
IPOS in English and Chinese showed good validity, good internal consistency, and good test-retest reliability, except for the Communication and Practical Issues subscale. There was poor inter-rater reliability between patients and staff.
Transformer-based deep neural network language models for Alzheimer’s disease risk assessment from targeted speech
Authors: Roshanzamir Alireza , Aghajan Hamid , Soleymani Baghshah Mahdieh 
Published: March 2021

AbstractBackgroundWe developed transformer-based deep learning models based on natural language processing for early risk assessment of Alzheimer’s disease from the picture description test.MethodsThe lack of large datasets poses the most important limitation for using complex models that do not require feature engineering. Transformer-based pre-trained deep language models have recently made a large leap in NLP research and application. These models are pre-trained on available large datasets to understand natural language texts appropriately, and are shown to subsequently perform well on classification tasks with small training sets. The overall classification model is a simple classifier on top of the pre-trained deep language model.ResultsThe models are evaluated on picture description test transcripts of the Pitt corpus, which contains data of 170 AD patients with 257 interviews and 99 healthy controls with 243 interviews. The large bidirectional encoder representations from transformers (BERTLarge) embedding with logistic regression classifier achieves classification accuracy of 88.08%, which improves the state-of-the-art by 2.48%.ConclusionsUsing pre-trained language models can improve AD prediction. This not only solves the problem of lack of sufficiently large datasets, but also reduces the need for expert-defined features.
When time matters: a qualitative study on hospital staff’s strategies for meeting the target times in cancer patient pathways
Authors: Melby Line , Håland Erna 
Published: March 2021

Abstract
Background
Cancer patient pathways (CPPs) were introduced in Norway in 2015. CPPs are time-bound standardised care pathways that describe the organisation of and responsibilities for diagnostics and treatment, as well as communication with the patient and next of kin. The aim is to ensure that cancer patients experience a well-organised, coherent and predictable pathway without any delays in assessment and diagnostics caused by non-medical reasons. Preventing delays in diagnostics by meeting specific target times is central to the successful implementation of CPPs. The aim of this paper is to describe how hospital staff cope with the increased focus on meeting CPP target times and the measures and strategies implemented by hospitals and their staff.

Methods
Data for this paper were collected in a larger study on implementation and experiences with CPPs among hospital staff, general practitioners, and patients in Norway (2017–2020). The study had a qualitative cross-sectional design, and data were collected through interviews. This article is based on semi-structured interviews with hospital staff (N = 60) in five hospitals.

Results
Hospital staff are highly aware of the target times, and try to comply with them, in the interest of both the patients and the hospitals. The implementation of CPPs was not accompanied by the allocation of additional resources; therefore, hospitals could not simply increase capacity to meet the target times. Instead, they had to develop other strategies. Four categories of strategies were identified: (i) introducing new roles and more staff, (ii) reorganising the workflow, (iii) gaming the system and (iv) outsourcing services.

Conclusions
Hospital staff are torn between meeting the target times and a lack of resources and capacity. This is not unusual in the current healthcare context, where staff face organisational reforms and increasing demands on a regular basis. It is important to recognise frontline workers’ efforts towards realising new organisational changes. Therefore, carefully weighing the benefits against the costs and undertaking the necessary planning are important in the design and implementation of future care and treatment pathways for patients.
Molecular detection and genetic diversity of Rickettsia spp. in pet dogs and their infesting ticks in Harbin, northeastern China
Authors: Shao Jian-Wei , Yao Xin-Yan , Song Xu-Dong , Li Wen-Jun , Huang Hui-Lan , Huang Shu-Jian , Zhang Xue-Lian 
Published: March 2021

Abstract
Background
Pet dogs are important companion animals that share the environment within households, and play an important role in local community life. In addition, pet dogs also are reservoirs of zoonotic agents, including Rickettsia spp., thus increasing the risk of rickettsial infections in humans. It’s meaningful to investigate the epidemiology of rickettsial agents in pet dogs, and make contribute to the surveillance of rickettsioses in human in China.

Results
In this study, a total of 496 pet dogs’ blood samples and 343 ticks infested in pet dogs were collected, and the presence and prevalence of Rickettsia were determined by amplifying the partial gltA and 17-kDa genes, with an overall positive rate of 8.1 % in blood samples and 14.0 % in tick samples. In addition, the rrs, gltA, groEL, and ompA genes of rickettsial were also recovered to determine the species of Rickettsia detected furtherly. Sequencing blast and phylogenetic analyses revealed the presence of three human pathogenic Rickettsia species (Rickettsia raoultii, Candidatus Rickettsia tarasevichiae and Rickettsia felis) in samples associated with pet dogs. Moreover, all the sequences of Rickettsia that we obtained presented close relationship with others available in GenBank, and Rickettsia raoultii was the most predominant Rickettsia species infected in pet dogs’ blood samples or in tick samples.

Conclusions
This study provides the molecular epidemiology data about the Rickettsia spp. infection associated with pet dogs in urban areas of Harbin city. Three rickettisae species pathogenic to humans were identified from pet dogs’ blood and the infested ticks in urban areas of Harbin city. Considering the intimate relationship between human and pets, these results indicate the potential transmission risk of human rickettisal infections from pet dogs through ectoparasites, and also highlighting that more attention should be paid to rickettsial infection in pet dogs and the infested ticks from the “One health” perspective.
Induction of macrophage pyroptosis-related factors by pathogenic E. coli high pathogenicity island (HPI) in Yunnan Saba pigs
Authors: Shan Chunlan , Miao Shushu , Liu Chaoying , Zhang Bo , Zhao Weiwei , Wang Hao , Yang Wei , Cha Jinlong , Zhao Ru , Xiao Peng , Gao Hong 
Published: March 2021

Abstract
Background
Pyroptosis plays a pivotal role in the pathogenesis of many inflammatory diseases. The molecular mechanism by which pyroptosis is induced in macrophages following infection with pathogenic E. coli high pathogenicity island (HPI) will be evaluated in our study.

Results
After infection with the HPI+/HPI− strains and LPS, decreased macrophage cell membrane permeability and integrity were demonstrated with propidium iodide (PI) staining and the lactate dehydrogenase (LDH) assay. HPI+/HPI−-infection was accompanied by upregulated expression levels of NLRP3, ASC, caspase-1, IL-1β, IL-18 and GSDMD, with significantly higher levels detected in the HPI+ group compared to those in the HPI− group (P < 0.01 or P < 0.05). HPI+ strain is more pathogenic than HPI− strain.

Conclusion
Our findings indicate that pathogenic E. coli HPI infection of Saba pigs causes pyroptosis of macrophages characterized by upregulated expression of pyroptosis key factors in the NLRP3/ASC/caspase-1 signaling pathway, direct cell membrane pore formation, and secretion of the inflammatory factor IL-1β and IL-18 downstream of NLRP3 and caspase-1 activation to enhance the inflammatory response.
Genetically determined tobacco and alcohol use and risk of atrial fibrillation
Authors: Lu Yunlong , Guo Yan , Lin Hefeng , Wang Zhen , Zheng Liangrong 
Published: March 2021

AbstractBackgroundThe causality between the use of alcohol and cigarettes and atrial fibrillation (AF) remains controversial. We conducted a Mendelian randomization (MR) study to evaluate the association of genetic variants related to tobacco and alcohol use with AF.MethodsSingle nucleotide polymorphisms (SNPs) related to smoking initiation (N = 374), age at initiation of regular smoking (N = 10), cigarettes per day (N = 55), and smoking cessation (N = 24) were derived from a genome-wide association studies (GWAS) of tobacco use (N = 1.2 million individuals). SNPs related to heavy alcohol use (N = 6) were derived from a GWAS of UK biobank (N = 125,249 individuals). The genetically matching instrumented variables were obtained from the GWAS of AF (N = 588,190 individuals). The estimates between tobacco and alcohol use and AF were combined by inverse-variance weighted (IVW), simple median, weighted median, MR-robust adjusted profile score method, MR-PRESSO, and multivariable MR.ResultsA total of 65,446 AF patients and 522,744 referents were included. In the IVW analysis, the odds ratio per one-unit increase of smoking initiation was 1.11 (95% CI, 1.06–1.16;P = 3.35 × 10−6) for AF. Genetically predicted age at initiation of regular smoking, cigarettes per day and smoking cessation were not associated with AF. The IVW estimate showed that heavy alcohol consumption increased AF risk (OR, 1.11; 95% CI, 1.04–1.18;P = 0.001). The results were consistent in complementary analyses and multivariable MR.ConclusionOur MR study indicated that regular smoking was associated with increased risk of AF, no matter the age at initiation of regular smoking, or the number of cigarettes smoked per day. Genetically predicted heavy alcohol consumption increased the risk of AF.
Comparative metabolomics analysis of amphotericin B high-yield mechanism for metabolic engineering
Authors: Zhang Bo , Chen Yu , Jiang Sheng-Xian , Cai Xue , Huang Kai , Liu Zhi-Qiang , Zheng Yu-Guo 
Published: March 2021

Abstract
Background
The polyene macrocyclic compound amphotericin B (AmB) is an important antifungal antibiotic for the clinical treatment of invasive fungal infections. To rationally guide the improvement of AmB production in the main producing strain Streptomyces nodosus, comparative metabolomics analysis was performed to investigate the intracellular metabolic changes in wild-type S. nodosus ZJB20140315 with low-yield AmB production and mutant S. nodosus ZJB2016050 with high-yield AmB production, the latter of which reached industrial criteria on a pilot scale.

Results
To investigate the relationship of intracellular metabolites, 7758 metabolites were identified in mutant S. nodosus and wildtype S. nodosus via LC–MS. Through analysis of metabolism, the level of 26 key metabolites that involved in carbon metabolism, fatty acids metabolism, amino acids metabolism, purine metabolism, folate biosynthesis and one carbon pool by folate were much higher in mutant S. nodosus. The enrichment of relevant metabolic pathways by gene overexpression strategy confirmed that one carbon pool by folate was the key metabolic pathway. Meanwhile, a recombinant strain with gene metH (methionine synthase) overexpressed showed 5.03 g/L AmB production within 120 h fermentation, which is 26.4% higher than that of the mutant strain.

Conclusions
These results demonstrated that comparative metabolomics analysis was an effective approach for the improvement of AmB production and could be applied for other industrially or clinically important compounds as well.
MicroRNA-1182 and let-7a exert synergistic inhibition on invasion, migration and autophagy of cholangiocarcinoma cells through down-regulation of NUAK1
Authors: Pan Xin , Wang Gang , Wang Baoming 
Published: March 2021

Abstract
Background
Cholangiocarcinoma (CCA) is the second most common primary liver malignancy worldwide. Several microRNAs (miRNAs) have been implicated as potential tumor suppressors in CCA. This study aims to explore the potential effects of miR-1182 and let-7a on CCA development.

Methods
Bioinformatics analysis was conducted to screen differentially expressed genes in CCA, Western blot analysis detected NUAK1 protein expression and RT-qPCR detected miR-1182, let-7a and NUAK1 expression in CCA tissues and cell lines. Dual luciferase reporter gene assay and RIP were applied to validate the relationship between miR-1182 and NUAK1 as well as between let-7a and NUAK1. Functional experiment was conducted to investigate the role of miR-1182, let-7a and NUAK1 in cell migration, proliferation and autophagy. Then, the CCA cells that received various treatments were implanted to mice to establish animal model, followed by tumor observation and HE staining to evaluate lung metastasis.

Results
CCA tissues and cells were observed to have a high expression of NUAK1 and poor expression of miR-1182 and let-7a. NUAK1 was indicated as a target gene of miR-1182 and let-7a. Importantly, upregulation of either miR-1182 or let-7a induced autophagy, and inhibited cell progression and in vivo tumor growth and lung metastasis; moreover, combined treatment of miR-1182 and let-7a overexpression presented with enhanced inhibitory effect on NUAK1 expression and CCA progression, but such synergistic effect could be reversed by overexpression of NUAK1.

Conclusion
Taken together, the findings suggest the presence of a synergistic antitumor effect of miR-1182 and let-7a on the development of CCA via the down-regulation of NUAK1, providing novel insight into the targeted therapy against CCA.
Effect on 30-day mortality and duration of hospitalization of empirical antibiotic therapy in CRGNB-infected pneumonia
Authors: Li Rongrong , Tang Hao , Xu Huaming , Cui Kunwei , Li Shujin , Shen Jilu 
Published: March 2021

AbstractBackgroundThe objective of this study was to investigate whether unreasonable empirical antibiotic treatment (UEAT) had an impact on 30-day mortality and duration of hospitalization in bacterial pneumonia caused by carbapenem-resistant gram-negative bacteria (CRGNB).MethodsThis was a retrospective cohort study involving CRGNB-infected pneumonia. All CRGNB-infected pneumonia patients received empirical and targeted antibiotic treatment (TAT), and they were divided into reasonable empirical antibiotic treatment (REAT) and UEAT according to whether the empirical antibiotic treatment (EAT) was reasonable. The data of the two groups were compared to analyze their influence on the 30-day mortality and hospitalization time in CRGNB-infected pneumonia patients. Moreover, we also considered other variables that might be relevant and conducted multivariable regression analysis of 30-day mortality and duration of hospitalization in CRGNB-infected pneumonia patients.ResultsThe study collected 310 CRGNB-infected pneumonia patients, the most common bacterium isAcinetobacter baumannii(211/310 [68%]), the rest wereKlebsiella pneumoniae(46/310 [15%]),Pseudomonas aeruginosaand others (53/310 [17%]). Among them, 76/310 (24.5%) patients received REAT. In the analysis of risk factors, dementia, consciousness were risk factors of 30-day mortality, pulmonary disease, hemodynamic support at culture taken day and recent surgery were risk factors for longer hospital stay. The analysis of 30-day mortality showed that UEAT was not associated with 30-day mortality for the 30-day mortality of REAT and UEAT were 9 of 76 (11.84%) and 36 of 234 (15.38%) (P = 0.447), respectively. Meanwhile, there was difference between REAT and UEAT (P = 0.023) in the analysis of EAT on hospitalization time in CRGNB-infected pneumonia patients.ConclusionsUEAT was not associated with 30-day mortality while was related to duration of hospitalization in CRGNB-infected pneumonia patients, in whichAcinetobacter baumanniiiaccouned for the majority.
Chordomas and chondrosarcomas of the skull base: treatment and outcome analysis in a consecutive case series of 24 patients
Authors: Metcalfe Christopher , Muzaffar Jameel , Kulendra Kevin , Sanghera Paul , Shaw Simon , Shad Amjad , Saravanappa Natarajan , Paluzzi Alessandro , Ahmed Shahzada 
Published: March 2021

Abstract
Background
We present our 9-year consecutive case series of skull base chordomas and chondrosarcomas from a UK tertiary referral centre, discussing treatments offered and outcomes. This was carried out to improve understanding around current treatment and to better inform the management of future patients.

Methods
Consecutive case series over a 9-year period (2007–2016). Retrospective data analysis from the electronic skull base multidisciplinary team database and the digital patient records at a UK tertiary referral centre

Results
Twenty-four patients were identified (11 chordomas, 13 chondrosarcomas, mean age 52). Nineteen had proton beam therapy (PBT) postoperatively; two had intensity-modulated radiotherapy; two had no further treatment. One patient was lost to follow-up. All chordomas were resected via a transnasal endoscopic approach. Of the 19 patients undergoing resection with PBT, 13 were disease free at latest follow-up, and six patients had local recurrence, of which two died (mean follow up 7.4 years). Of the three patients treated with surgery then IMRT/TomoTherapy, one died 4 years post-treatment, and the other two are alive after 4 and 5 years of follow-up respectively. Of the two patients treated with surgery alone, one was lost to follow-up, and the other is alive after more than 8 years. Chondrosarcoma 5-year survival was 91.6%, and chordoma 4-year survival was 75%.

Conclusion
Skull base chordomas and chondrosarcomas can be challenging to resect, and most cases require adjuvant therapy to achieve control. Where complete resection is not possible, it is critical to undertake sufficient resection to permit high-dose radiation.
Expression of Talin-1 in endometriosis and its possible role in pathogenesis
Authors: Tang Xian , Li Qing , Li Lijie , Jiang Jianfa 
Published: March 2021

Abstract
Background
Endometriosis is a disease that involves active cell invasion and migration. Talin-1 can promote cell invasion, migration and adhension in various cancer cells, but its role in endometriosis has not been investigated. This study was to investigate the expression level of Talin-1 in endometriosis and the role of Talin-1 in the proliferation, adhesion, migration, and invasion of human endometrial stromal cells (ESCs).

Methods
Ectopic and eutopic endometrial tissues were collected from women with endometriosis, and the control endometrial tissues were obtained from patients without endometriosis. The expression level of Talin-1 was detected in each sample using quantitative real-time polymerase chain reaction and immunohistochemistry. The expression of Talin-1 was inhibited using RNA interference in ESCs, and its proliferation, apoptosis, adhesion, migration, and invasion capacity were analyzed. Western blotting was performed to detect the expression of related molecules after the downregulation of Talin-1.

Results
The results showed that the mRNA and protein expression of Talin-1 were significantly increased in the ectopic endometrium and eutopic endometrial tissues compared with the controls. The knockdown of Talin-1 did not affect the proliferation and apoptosis of ESCs. The results indicated that the downexpression of Talin-1 inhibited the adhesion, invasion, and migration of ESCs. In addition, the expressions of N-cadherin, MMP-2, and integrin β3 were significantly lower after the deregulation of Talin-1, whereas the levels of E-cadherin were significantly increased.

Conclusions
The expression of Talin-1 was increased in the ectopic and eutopic endometrial tissues compared with the control endometrium. The downregulation of Talin-1 inhibited the adhesion, invasion, and migration of ESCs.
Proximal deep vein thrombosis and pulmonary embolism in COVID-19 patients: a systematic review and meta-analysis
Authors: Longchamp Gregoire , Manzocchi-Besson Sara , Longchamp Alban , Righini Marc , Robert-Ebadi Helia , Blondon Marc 
Published: March 2021

Abstract
Background
COVID-19 appears to be associated with a high risk of venous thromboembolism (VTE). We aimed to systematically review and meta-analyze the risk of clinically relevant VTE in patients hospitalized for COVID-19.

Methods
This meta-analysis included original articles in English published from January 1st, 2020 to June 15th, 2020 in Pubmed/MEDLINE, Embase, Web of science, and Cochrane. Outcomes were major VTE, defined as any objectively diagnosed pulmonary embolism (PE) and/or proximal deep vein thrombosis (DVT). Primary analysis estimated the risk of VTE, stratified by acutely and critically ill inpatients. Secondary analyses explored the separate risk of proximal DVT and of PE; the risk of major VTE stratified by screening and by type of anticoagulation.

Results
In 33 studies (n = 4009 inpatients) with heterogeneous thrombotic risk factors, VTE incidence was 9% (95%CI 5–13%, I2 = 92.5) overall, and 21% (95%CI 14–28%, I2 = 87.6%) for patients hospitalized in the ICU. Proximal lower limb DVT incidence was 3% (95%CI 1–5%, I2 = 87.0%) and 8% (95%CI 3–14%, I2 = 87.6%), respectively. PE incidence was 8% (95%CI 4–13%, I2 = 92.1%) and 17% (95%CI 11–25%, I2 = 89.3%), respectively. Screening and absence of anticoagulation were associated with a higher VTE incidence. When restricting to medically ill inpatients, the VTE incidence was 2% (95%CI 0–6%).

Conclusions
The risk of major VTE among COVID-19 inpatients is high but varies greatly with severity of the disease. These findings reinforce the need for the use of thromboprophylaxis in all COVID-19 inpatients and for clinical trials testing different thromboprophylaxis regimens in subgroups of COVID-19 inpatients.

Trial registration
The review protocol was registered in PROSPERO International Prospective Register of Systematic Reviews (CRD42020193369).