bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome sequencing reveals underdiagnosis of primary ciliary dyskinesia in bronchiectasis
Authors: Shoemark Amelia , Griffin Helen , Wheway Gabrielle , Hogg Claire , Lucas Jane S. ,   Genomics England Research Consortium, Camps Carme , Taylor Jenny , Carroll Mary , Loebinger Michael R. , Chalmers James D. , Morris-Rosendahl Deborah , Mitchison Hannah M. , De Soyza Anthony ,   The Genomics England Research Consortium:, Brown D. , Ambrose J.C. , Arumugam P. , Bevers R. , Bleda M. , Boardman-Pretty F. , Boustred C.R. , Brittain H. , Caulfield M.J. , Chan G.C. , Fowler T. , Giess A. , Hamblin A. , Henderson S. , Hubbard T.J.P. , Jackson R. , Jones L.J. , Kasperaviciute D. , Kayikci M. , Kousathanas A. , Lahnstein L. , Leigh S.E.A. , Leong I.U.S. , Lopez F.J. , Maleady-Crowe F , McEntagart M. , Minneci F. , Moutsianas L. , Mueller M. , Murugaesu N. , Need A.C. , O'Donovan P. , Odhams C.A. , Patch C. , Perez-Gil D. , Pereira M.B. , Pullinger J. , Rahim T. , Rendon A. , Rogers T. , Savage K. , Sawant K. , Scott R.H. , Siddiq A. , Sieghart A. , Smith S.C. , Sosinsky A. , Stuckey A. , Tanguy M. , Taylor Tavares A.L. , Thomas E.R.A. , Thompson S.R. , Tucci A. , Welland M.J. , Williams E. , Witkowska K. , Wood S.M. 
Published: June 2022

BackgroundBronchiectasis can result from infectious, genetic, immunological and allergic causes. 60–80% of cases are idiopathic, but a well-recognised genetic cause is the motile ciliopathy, primary ciliary dyskinesia (PCD). Diagnosis of PCD has management implications including addressing comorbidities, implementing genetic and fertility counselling and future access to PCD-specific treatments. Diagnostic testing can be complex; however, PCD genetic testing is moving rapidly from research into clinical diagnostics and would confirm the cause of bronchiectasis.MethodsThis observational study used genetic data from severe bronchiectasis patients recruited to the UK 100,000 Genomes Project and patients referred for gene panel testing within a tertiary respiratory hospital. Patients referred for genetic testing due to clinical suspicion of PCD were excluded from both analyses. Data were accessed from the British Thoracic Society audit, to investigate whether motile ciliopathies are underdiagnosed in people with bronchiectasis in the UK.ResultsPathogenic or likely pathogenic variants were identified in motile ciliopathy genes in 17 (12%) out of 142 individuals by whole-genome sequencing. Similarly, in a single centre with access to pathological diagnostic facilities, 5–10% of patients received a PCD diagnosis by gene panel, often linked to normal/inconclusive nasal nitric oxide and cilia functional test results. In 4898 audited patients with bronchiectasis, <2% were tested for PCD and <1% received genetic testing.ConclusionsPCD is underdiagnosed as a cause of bronchiectasis. Increased uptake of genetic testing may help to identify bronchiectasis due to motile ciliopathies and ensure appropriate management.
High serum levels of N-epsilon-carboxymethyllysine are associated with poor coronary collateralization in type 2 diabetic patients with chronic total occlusion of coronary artery
Authors: Li Le-Ying , Chen Shuai , Li Fei-Fei , Wu Zhi-Ming , Shen Ying , Ding Feng-Hua , Wang Xiao-Qun , Shen Wei-Feng , Chen Qiu-Jing , Dai Yang , Lu Lin 
Published: June 2022

Abstract
Background
The formation of advanced glycation end-products (AGEs) is a crucial risk factor for the pathogenesis of cardiovascular diseases in diabetes. We investigated whether N-epsilon-carboxymethyllysine (CML), a major form of AGEs in vivo, was associated with poor coronary collateral vessel (CCV) formation in patients with type 2 diabetes mellitus (T2DM) and chronic total occlusion (CTO) of coronary artery.

Methods
This study consisted of 242 T2DM patients with coronary angiographically documented CTO. Blood samples were obtained and demographic/clinical characteristics were documented. The coronary collateralization of these patients was defined according to Rentrop or Werner classification. Serum CML levels were evaluated using ELISA assay. Receiver operating characteristic curve and multivariable regression analysis were performed.

Results
242 patients were categorized into poor CCV group or good CCV group (107 vs. 135 by the Rentrop classification or 193 vs. 49 by the Werner classification, respectively). Serum CML levels were significantly higher in poor CCV group than in good CCV group (110.0 ± 83.35 vs. 62.95 ± 58.83 ng/ml by the Rentrop classification and 94.75 ± 78.29 ng/ml vs. 40.37 ± 28.69 ng/ml by Werner classification, both P < 0.001). Moreover, these CML levels were also significantly different across the Rentrop and Werner classification subgroups (P < 0.001). In multivariable logistic regression, CML levels (P < 0.001) remained independent determinants of poor CCV according to the Rentrop or Werner classification after adjustment of traditional risk factors.

Conclusions
This study suggests that higher serum CML level is associated with poor collateralization in T2DM patients with CTO.
Development and validation of reassigned CEA, CYFRA21-1 and NSE-based models for lung cancer diagnosis and prognosis prediction
Authors: Yuan Jingmin , Sun Yan , Wang Ke , Wang Zhiyi , Li Duo , Fan Meng , Bu Xiang , Chen Jun , Wu Zhiquan , Geng Hui , Wu Jiamei , Xu Ying , Chen Mingwei , Ren Hui 
Published: June 2022

Abstract
Background
The majority of lung cancer(LC) patients are diagnosed at advanced stage with a poor prognosis. However, there is still no ideal diagnostic and prognostic prediction model for lung cancer.

Methods
Data of CEA, CYFRA21-1 and NSE test of patients with LC and benign lung diseases (BLDs) or healthy people from Physical Examination Center was collected. Samples were divided into three data sets as needed. Reassign three kinds of tumor markers (TMs) according to their distribution characteristics in different populations. Diagnostic and prognostic models were thus established, and independent validation was conducted with other data sets.

Results
The diagnostic prediction model showed good discrimination ability: the area under the receiver operating characteristic curve (AUC) differentiated LC from healthy people and BLDs (diagnosed within 2 months), being 0.88 and 0.84 respectively. Meanwhile, the prognostic prediction model did great in prediction: AUC in training data set and test data set were 0.85 and 0.8 respectively.

Conclusion
Reassigned CEA, CYFRA21-1 and NSE can effectively predict the diagnosis and prognosis of LC. Compared with the same TMs that were considered individually, this diagnostic prediction model can identify high-risk population for LC screening more accurately. The prognostic prediction model could be helpful in making more scientific treatment and follow-up plans for patients.
Exploring the digital footprint of depression: a PRISMA systematic literature review of the empirical evidence
Authors: Zarate Daniel , Stavropoulos Vasileios , Ball Michelle , de Sena Collier Gabriel , Jacobson Nicholas C. 
Published: June 2022

Abstract
Background
This PRISMA systematic literature review examined the use of digital data collection methods (including ecological momentary assessment [EMA], experience sampling method [ESM], digital biomarkers, passive sensing, mobile sensing, ambulatory assessment, and time-series analysis), emphasizing on digital phenotyping (DP) to study depression. DP is defined as the use of digital data to profile health information objectively.

Aims
Four distinct yet interrelated goals underpin this study: (a) to identify empirical research examining the use of DP to study depression; (b) to describe the different methods and technology employed; (c) to integrate the evidence regarding the efficacy of digital data in the examination, diagnosis, and monitoring of depression and (d) to clarify DP definitions and digital mental health records terminology.

Results
Overall, 118 studies were assessed as eligible. Considering the terms employed, “EMA”, “ESM”, and “DP” were the most predominant. A variety of DP data sources were reported, including voice, language, keyboard typing kinematics, mobile phone calls and texts, geocoded activity, actigraphy sensor-related recordings (i.e., steps, sleep, circadian rhythm), and self-reported apps’ information. Reviewed studies employed subjectively and objectively recorded digital data in combination with interviews and psychometric scales.

Conclusions
Findings suggest links between a person’s digital records and depression. Future research recommendations include (a) deriving consensus regarding the DP definition and (b) expanding the literature to consider a person’s broader contextual and developmental circumstances in relation to their digital data/records.
Influencing factors of attitudes towards death and demands for death education among community-dwelling Chinese older adults: a cross-sectional study
Authors: Lei Lei , Zhao Hongyan , Ran Lijuan , Wang Lihua , Luo Yu 
Published: June 2022

Abstract
Background
Considering older adults are getting closer to the end-of-life and face death more directly. Attitudes to death not only affect the physical and mental health of older adults, but also affect their acceptance of hospice care, even the quality of death. This study aims to explore the status, influencing factors of attitudes toward death and demands of death education among the community-dwelling older adults in southwestern China.

Methods
A cross-sectional survey was adopted to investigate 683 community-dwelling older adults in Chongqing, China. Non-parametric test and multiple linear regression analysis was used to explore the influencing factors of different attitudes toward death of older adults in community.

Results
The multiple linear regression models showed that different dimensions of death attitudes were affected by one or more factors including number of diseases, discussion about life and death, marital status, and average income per month. And community-dwelling older adults have high level demand for death education.

Conclusions
Under the taboo culture of death in China, this study is one of the few studies on the attitudes toward death and the demands for death education of the community-dwelling older adults. This study contributes to enrich the global death studies and provide reference for the death education for older adults.
The impact of the union of lesser trochanter fragments after intramedullary fixation of trochanteric femoral fractures: an X-ray based study
Authors: You Jiongming , Wang Feng , Li Feng , Wu Yinsheng , Wang Yong , Chen Zifei 
Published: June 2022

Abstract
Background
Displacement of the lesser trochanter (LT) is not uncommon after managing intertrochanteric femoral fractures and the influence of nonunion of the LT-fragment on clinical outcomes remains controversial. This study aimed to investigate the relationship between the displacement distance and union of the LT-fragment and evaluate the influence of LT-fragment nonunion on hip function and complications.

Methods
This retrospective study included patients with intertrochanteric fractures and displaced LT treated with intramedullary fixation at Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine from June 2015 to July 2017. The patients were grouped as union and nonunion of the LT-fragment at 1 year. The LT-fragment displacement distance of LT was measured by the anterior–posterior radiographs.

Results
Thirty-one and 22 patients showed union and nonunion at 1 year, respectively. The nonunion group had a higher postoperative complication rate than the union group (59% vs. 29%, P = 0.047), especially mechanical complications (45% vs. 6%, P = 0.001). There was no significant difference in hip function between the two groups (P > 0.05). The receiver operating characteristic (ROC) curve revealed an area under the curve of 0.933 of displacement ratio. Patients with a displacement ratio > 0.35 were more likely to have nonunion of the LT-fragment.

Conclusions
The displacement ratio might be a reliable predictor of LT-fragment union. The incidence of postoperative complications might increase with LT-fragment nonunion.
Outcomes and management of delayed complication after severe blunt liver injury
Authors: Kagoura Masaaki , Monden Kazuteru , Sadamori Hiroshi , Hioki Masayoshi , Ohno Satoshi , Takakura Norihisa 
Published: June 2022

Abstract
Background
The treatment of delayed complications after liver trauma such as bile leakage (BL) and hepatic artery pseudoaneurysms (HAPs) is difficult. The purpose of this study is to investigate the outcomes and management of post-traumatic BL and HAPs.

Methods
We retrospectively evaluated patients diagnosed with blunt liver injury, graded by the American Association for the Surgery of Trauma Liver Injury Scale, who were admitted to our hospital between April 2010 and December 2019. Patient characteristics and treatments were analyzed.

Results
A total of 176 patients with blunt liver injury were evaluated. Patients were diagnosed with grade I–II liver injury (n = 127) and with grade III-V injury (n = 49). BL was not observed in patients with grade I–II injury. Eight patients with grade III-V injury developed BL: surgical intervention was not needed for six patients with peripheral bile duct injury, but hepaticojejunostomy was needed for two patients with central bile duct injury. Out of 10 patients with HAPs, only three with grade I–II injury and one with grade III–V were treated conservatively; the rest six with grade III-V injury required transcatheter arterial embolization (TAE). All pseudoaneurysms disappeared.

Conclusions
Severe blunt liver injury causing peripheral bile duct injury can be treated conservatively. In contrast, the central bile duct injury requires surgical treatment. HAPs with grade I–II injury might disappear spontaneously. HAPs with grade III–V injury should be considered TAE.
Correlation between alveolar cleft morphology and the outcome of secondary alveolar bone grafting for unilateral cleft lip and palate
Authors: Yu Xinlei , Huang Yiping , Li Weiran 
Published: June 2022

Abstract
Background
Secondary alveolar bone grafting (SABG) is an integral part of the treatment for cleft lip and alveolus and cleft lip and palate. However, the outcome of SABG was not satisfactory as expected, factors that affecting the outcome were still controversial. The aims of this study were to summarize a new method for the classification of alveolar cleft morphology in patients with unilateral cleft lip and alveolus or unilateral cleft lip and palate, to evaluate the correlation between the morphology and SABG outcomes, to identify factors that might predict the outcomes.

Methods
The characteristics of the cleft morphologies of 120 patients who underwent SABG were observed using the preoperative Cone-Beam Computed Tomography (CBCT) images. 52 patients who had CBCT scans performed at least 6 months after SABG were included for the evaluation of outcomes. Both categorical and continuous evaluation methods were measured. Correlations between cleft morphology and SABG outcomes were assessed using the Pearson correlation coefficient in SPSS 27.0.0.

Results
A new method for the classification of cleft morphology was summarized:type I, prism type (labial defect size ≥ palatal defect size; nasal defect size ≥ occlusal defect size); type II, prism’ type (labial defect ≥ palatal defect; nasal defect < occlusal defect); type III, inverted prism type (palatal defect ≥ labial defect); type IV, funnel type (presented as a significantly narrow defect area in the middle towards the vertical dimension); and type V, undefinable (extremely irregular morphology can’t be defined as any of the above types). Categorical evaluation showed 8 failure, 11 poor, 12 moderate, and 21 good results, while the average bone filling rate was 59.24 ± 30.68%. There was a significant correlation between the cleft morphology and categorical/continuous evaluation outcome (p < 0.05).

Conclusion
The new method for the classification of alveolar cleft morphology summarized in this study was comprehensive and convenient for clinical application. Both categorical and continuous methods should be used for radiographic assessments in patients undergoing SABG. The chances of a successful procedure might be better when the patient has type I or IV morphology, in which the shape is like a funnel in the relatively palatal or occlusal area towards the vertical dimension. A relatively great amount of bone resorption was observed in most patients.
Trial registration Chinese clinical trial registry; registration number: ChiCTR2100054438.
Virtual reality as a teaching method for resuscitation training in undergraduate first year medical students during COVID-19 pandemic: a randomised controlled trial
Authors: Moll-Khosrawi Parisa , Falb Alexander , Pinnschmidt Hans , Zöllner Christian , Issleib Malte 
Published: June 2022

AbstractBackgroundVirtual reality (VR) is a computer-generated simulation technique which yields plenty of benefits and its application in medical education is growing. This study explored the effectiveness of a VR Basic Life Support (BLS) training compared to a web-based training during the COVID-19 pandemic, in which face-to-face trainings were disrupted or reduced.MethodsThis randomised, double-blinded, controlled study, enrolled 1styear medical students. The control group took part in web-based BLS training, the intervention group received an additional individual VR BLS training. The primary endpoint was the no-flow time-an indicator for the quality of BLS-, assessed during a structural clinical examination, in which also the overall quality of BLS (secondary outcome) was rated. The tertiary outcome was the learning gain of the undergraduates, assessed with a comparative self-assessment (CSA).ResultsData from 88 undergraduates (n = 46 intervention- andn = 42 control group) were analysed. The intervention group had a significant lower no-flow time (p = .009) with a difference between the two groups of 28% (95%-CI [8%;43%]). The overall BLS performance of the intervention group was also significantly better than the control group with a mean difference of 15.44 points (95%-CI [21.049.83]),p < .001. In the CSA the undergraduates of the intervention group reported a significant higher learning gain.ConclusionVR proved to be effective in enhancing process quality of BLS, therefore, the integration of VR into resuscitation trainings should be considered. Further research needs to explore which combination of instructional designs leads to deliberate practice and mastery learning of BLS.
Relational aspects of building capacity in economic evaluation in an Australian Primary Health Network using an embedded researcher approach
Authors: Piper Donella , Jorm Christine , Iedema Rick , Goodwin Nicholas , Searles Andrew , McFayden Lisa 
Published: June 2022

Abstract
Background
Health organisations are increasingly implementing ‘embedded researcher’ models to translate research into practice. This paper examines the impact of an embedded researcher model known as the embedded Economist (eE) Program that was implemented in an Australian Primary Health Network (PHN) located in regional New South Wales, Australia. The site, participants, program aims and design are described. Insights into the facilitators, challenges and barriers to the integration of economic evaluation perspectives into the work of the PHN are provided.

Methods
The eE Program consisted of embedding a lead health economist on site, supported by offsite economists, part-time, for fifteen weeks to collaborate with PHN staff. Evaluation of the eE at the PHN included qualitative data collection via semi-structured interviews (N= 34), observations (N=8) and a field diary kept by the embedded economists. A thematic analysis was undertaken through the triangulation of this data.

Results
The eE Program successfully met its aims of increasing PHN staff awareness of the value of economic evaluation principles in decision-making and their capacity to access and apply these principles. There was also evidence that the program resulted in PHN staff applying economic evaluations when commissioning service providers. Evaluation of the eE identified two key facilitators for achieving these results. First, a highly receptive organisational context characterised by a work ethic, and site processes and procedures that were dedicated to improvement. Second was the development of trusted relationships between the embedded economist and PHN staff that was enabled through: the commitment of the economist to bi-directional learning; facilitating access to economic tools and techniques; personality traits (likeable and enthusiastic); and because the eE provided ongoing support for PHN projects beyond the fifteen-week embedding period.

Conclusions
This study provides the first detailed case description of an embedded health economics program. The results demonstrate how the process, context and relational factors of engaging and embedding the support of a health economist works and why. The findings reinforce international evidence in this area and are of practical utility to the future deployment of such programs.
Small extracellular vesicles derived from dermal fibroblasts promote fibroblast activity and skin development through carrying miR-218 and ITGBL1
Authors: Zou Qin , Zhang Mei , Yuan Rong , Wang Yifei , Gong Zhengyin , Shi Rui , Li Yujing , Fei Kaixin , Luo Chenggang , Xiong Ying , Zheng Ting , Zhu Li , Tang Guoqing , Li Mingzhou , Li Xuewei , Jiang Yanzhi 
Published: June 2022

AbstractSkin thickness is closely related to the appearance of human skin, such as sagging and wrinkling, which primarily depends on the level of collagen I synthesized by dermal fibroblasts (DFs). Small extracellular vesicles (SEVs), especially those derived from human DFs (HDFs), are crucial orchestrators in shaping physiological and pathological development of skin. However, the limited supply of human skin prevents the production of a large amount of HDFs-SEVs, and pig skin is used as a model of human skin. In this study, SEVs derived from DFs of Chenghua pigs (CH-SEVs), considered to have superior skin thickness, and Large White pigs (LW-SEVs) were collected to compare their effects on DFs and skin tissue. Our results showed that, compared with LW-SEVs, CH-SEVs more effectively promoted fibroblast proliferation, migration, collagen synthesis and contraction; in addition, in mouse model injected with both SEVs, compared with LW-SEVs, CH-SEVs increased the skin thickness and collagen I content more effectively. Some differentially expressed miRNAs and proteins were found between CH-SEVs and LW-SEVs by small RNA-seq and LC–MS/MS analysis. Interestingly, we identified that CH-SEVs were enriched in miRNA-218 and ITGBL1 protein, which played important roles in promoting fibroblast activity via activation of the downstream TGFβ1-SMAD2/3 pathway in vitro. Furthermore, overexpression of miRNA-218 and ITGBL1 protein increased the thickness and collagen I content of mouse skin in vivo. These results indicate that CH-SEVs can effectively stimulate fibroblast activity and promote skin development and thus have the potential to protect against and repair skin damage.
Graphical Abstract