bluuebunny/crossref_metadata_2025 huggingface dataset:
Deploying Machine Learning to Validate Clinical Phenotypes and Factors Associated with Mortality risk in 2,022 Critically Ill Patients with COVID-19 in Spain
Authors: Rodríguez Alejandro , Botella Manuel Ruiz , Matín-Loeches Ignacio , Herrera María Jiménez , Solé-Violan Jordi , Gómez Josep , Bodí María , Trefler Sandra , Papiol Elisabeth , Díaz Emili , Suberviola Borja , Vallverdú Montserrat , Mayor-Vázquez Eric , Moreno Antonio Albaya , Berlanga Alfonso Canabal , Sánchez Miguel , Ortíz María del Valle , Ballesteros Juan Carlos , Iglesias Lorena Martín , Marín-Corral Judith , Ramos Esther López , Valverde Virgina Hidalgo , Tello Loreto Vidaur , Chinesta Susana Sancho , de Molina Francisco Javier González , García Sandra Herrero , Perez Carmen Carolina Sena , Laderas Juan Carlos Pozo , García Raquel Rodríguez , Estella Angel , Ferrer Ricard
Published: December 2020

Background: The identification of factors associated with Intensive Care Unit (ICU) mortality and derived clinical phenotypes in COVID-19 patients could help for a more tailored approach to clinical decision-making that improves prognostic outcomes. Methods: Prospective, multicenter, observational study of critically ill patients with confirmed COVID-19 disease and acute respiratory failure admitted from 63 Intensive Care Units(ICU) in Spain. The objective was to analyze patient’s factors associated with mortality risk and utilize a Machine Learning(ML) to derive clinical COVID-19 phenotypes. Patient features including demographics and clinical data at ICU admission were analyzed. Generalized linear models were used to determine ICU morality risk factors. An unsupervised clustering analysis was applied to determine presence of phenotypes. The prognostic models were validated and their performance was measured using accuracy test, sensitivity, specificity and ROC curves. Results: The database included a total of 2,022 patients (mean age 64[IQR5-71] years, 1423(70.4%) male, median APACHE II score (13[IQR10-17]) and SOFA score (5[IQR3-7]) points. The ICU mortality rate was 32.6%. Of the 3 derived phenotypes, the C(severe) phenotype was the most common (857;42.5%) and was characterized by the interplay of older age (>65 years), high severity of illness and a higher likelihood of development shock. The A(mild) phenotype (537;26.7%) included older age (>65 years), fewer abnormal laboratory values and less development of complications and B (moderate) phenotype (623,30.8%) had similar characteristics of A phenotype but were more likely to present shock. Crude ICU mortality was 45.4%, 25.0% and 20.3% for the C, B and A phenotype respectively. The ICU mortality risk factors and model performance differed between whole population and phenotype classifications.Conclusion: The presented ML model identified three clinical phenotypes that significantly correlated with host-response patterns and ICU mortality. Different risk factors across the whole population and clinical phenotypes were observed which may limit the application of a “one-size-fits-all” model in practice. Funding: None
Too Tight or Too Loose? The stringency of Mobility Restriction Policy Response by the Government of Sri Lanka against Covid-19
Authors: Wijesekara N.W.A.N.Y. , Herath H.D.B. , Kodithuwakku K.A.L.C. , Bulathsinghe B.A.M.P.
Published: December 2020

The Covid-19 pandemic has demanded governments to respond through policy measures on health systems, restriction of community mobility, and economic recovery. Policy measures on mobility included international and local travel restrictions, closure of schools and workplaces, work from home, cancellation or restriction of public gatherings, close of public transport, and stay at home orders. Sri Lanka too has embraced several policy measures restricting community mobility to curtail the outbreak. This paper analyzes the trend of stringency of Covid-19 mobility restriction policy response by the Government of Sri Lanka concerning its epidemiological trend, and with the same patterns observed in selected countries of the world. The Government Response Stringency Index (GRSI), a composite indicator developed by the Oxford Government Response Tracker (OxCGRT) group consisting of nine indicators based on publicly available data was used to track the stringency of policy measures related to mobility restrictions in Sri Lanka and the selected other countries. Besides, the daily number of Covid-19 cases in the same countries was analyzed. The results show that Sri Lanka was able to achieve 100% in the GRSI at the early stages of the outbreak, and most clusters it faced were curtailed under considerable high GRSI levels. GRSI values dropped to 26.85% just before the onset of the largest ever Minuwangoda Cluster, after which it was raised to 50%. Comparing GRSI values and epidemiological pattern of Sri Lanka with three purposefully selected blocks of countries showed that its stringency to be comparatively lower than most of the countries studied, as per the end of the study period. It could be seen that the current GRSI values about the policy measures adopted by the government of Sri Lanka are suboptimal, compared to the level of risk based on the case trend that the country is exposed to, as of 30th November 2020. These findings provide evidence towards the implementation of more stringent mobility control measures on an urgent basis, at least until the case number starts to fall.
Transforming UNICEF’s approach to Health System Strengthening: What place can a blended learning course play?
Authors: Naccarella Lucio , McPake Barbara , Dayal Prathna , Gikonyo Waithira , Torrealba Claudia Vivas , Morgan Alison
Published: December 2020

Background The United Nations Children’s Fund (UNICEF) published their Health Systems Strengthening (HSS) approach to meet its strategic goals of ending preventable maternal, newborn and child deaths and promoting the health and development of all children and reducing inequities in health in 2016. UNICEF commissioned the University of Melbourne’s Nossal Institute for Global Health to develop and deliver a pilot blended HSS program, involving 60 hours of online learning and two weeks of face-to-face teaching over a six- month period. To assess the extent to which the HSS program had built the first 83 UNICEF 2017 graduates’ capabilities to apply HSS actions by 2017, UNICEF funded an independent evaluator from the University of Melbourne. Methods A mixed-methods assessment was conducted using: online surveys of graduates at: enrolment, completion, 6-months post HSS program; nine focus groups with graduates at face-to-face workshops; and interviews with purposive samples of UNICEF graduates and graduate Senior Managers 12-months post HSS program. Results The HSS program content, structure and mode of delivery was positively received. Graduates reported increased confidence taking HSS actions and multiple changes in work practices (e.g., increased systems thinking and using of health system-based approaches). Graduates’ Senior Manager interviews revealed mixed impressions of graduates applying HSS actions, partly explained by the fit between the HSS program learnings and UNICEF’s workplace environment. Key contextual factors influencing graduates applying HSS actions included: workload; limited opportunities to apply HSS actions; limited HSS examples; and variable support to apply HSS actions. Graduate and Senior Manager suggestions to optimise applying HSS actions included: linking HSS program content with UNICEF priorities; increasing opportunities for graduates to apply HSS actions; increasing access to HSS support. Conclusions The paper concludes by presenting HSS program and assessment suggestions from the 2017 UNICEF Pilot HSS program assessment and actions taken for the 2018 UNICEF staff cohorts by HSS program developers, funders and beneficiaries.
Analytical Study of Buddha Sculptures in Jingyin Temple of Taiyuan, China
Authors: Bai Xiaojian , Jia Chen , Chen Zhigen , Gong Yuxuan , Cheng Huwei , Wang Jiayue
Published: December 2020

With exquisite design and unique style, the painted sculptures of Tutang Buddha and two attendants Buddha in Jingyin Temple are precious cultural heritages of China. The sculpture of Tutang Buddha, which was carved from a mound and painted by ancient craftsmen, was rarely found in ancient China. However, due to natural and human factors, the sculptures were severely damaged. Obviously, they require urgent and appropriate protection and restoration. In this study, samples taken from the sculptures were analysed through multiple analytical techniques, including scanning electron microscopy with energy dispersive spectrometry (SEM-EDS), Raman spectroscopy, X-ray diffraction (XRD), optical microscopy (OM) and granulometry. The analysis results enable us to infer the techniques used by the craftsmen in making the sculptures and provide a reliable evidence for the conservation and future protection of these and similar sculptures.
Reduced intensity of early intensification does not increase the risk of relapse in children with standard risk acute lymphoblastic leukemia - A multi-centric clinical study of GD-2008-ALL protocol
Authors: Li Xin-Yu , Li Jia-Qiang , Luo Xue-Qun , Wu Xue-Dong , Sun Xin , Xu Hong-Gui , Li Chang-Gang , Liu Ri-Yang , Sun Xiao-Fei , Chen Hui-Qin , Lin Yu-Deng , LI Chi-Kong , Fang Jian-Pei
Published: December 2020

Background The prognosis of childhood acute lymphoblastic leukemia (ALL) is optimistic with a 5-year event-free survival (EFS) rate of 70%-85%. However, the major causes of mortality are chemotherapy toxicity, infection and relapse. The Guangdong(GD)-2008-ALL collaborative protocol was carried out to study the effect of reduced intensity on treatment related mortality(TRM) based on Berlin-Frankfurt-Münster (BFM) 2002 backbone treatment. The study was designed to elucidate whether the reduced intensity is effective and safe for children with ALL. Methods The clinical data were obtained from February 28, 2008 to June 30, 2016. A total of 1,765 childhood ALL cases from 9 medical centers were collected and data were retrospectively analyzed. Patients were stratified into 3 groups according to bone marrow morphology, prednisone response, age, genotype, and karyotype information: standard risk (SR), intermediate risk (IR) and high risk (HR). For SR group, daunorubicin was decreased in induction IA while duration was reduced in Induction Ib (2 weeks in place of 4 weeks). Doses for CAM were same in all risk groups - SR patients received one CAM, others got two CAMs. Results The 5-year and 8-year overall survival (OS), event-free survival (EFS) and cumulative incidence of relapse (CIR) were 83.5±0.9% and 83.1±1.0%, 71.9±1.1% and 70.9±1.2%, and 19.5±1.0% and 20.5±1.1%, respectively. The 2-year treatment-related mortality (TRM) was 5.2±0.5%. The 5-year and 8-year OS were 90.7±1.4% and 89.6±1.6% in the SR group, while the 5-year and 8-year EFS were 81.5±1.8% and 80.0±2.0%. In the SR group, 74 (15.2 %) patients measured minimal residual disease (MRD) on Day 15 and Day 33 of induction therapy. Among them, 7 patients (9.46%) were MRD positive (≥ 0.01%) on Day 33. The incidence of relapse in the MRD Day33 positive group (n=7) was 28.6%, while in the MRD Day33 negative group (n=67) was 7.5% (p=0.129).Conclusions The results of GD-2008-ALL protocol are outstanding for reducing TRM in childhood ALL in China with excellent long term EFS. This protocol provided the evidence for further reducing intensity of induction therapy in the SR group according to the risk stratification. MRD levels on Day 15 and Day 33 are appropriate indexes for stratification.
Effects, barriers and facilitators in predischarge home assessments to improve the transition of care from the inpatient care to home in adult patients: An integrative review
Authors: Kirchner-Heklau Uta , Krause Kai , Saal Susanne
Published: December 2020

Background: Predischarge home assessments (PDHA) aim to support safe discharge from hospital or rehabilitation. There is insufficient evidence on the effectiveness of PDHA. For adults with any diagnosis, we aimed to determine (1) the effects of PDHA on outcomes associated with the successful return to community living (e.g., Activities of Daily Living, falls) and (2) the associated barriers and facilitators in order to derive recommendations for clinical practice.Methods: We searched Medline, EMBASE, CINAHL, five additional databases and other sources. We included individual and cluster randomized (RCT/cRCT) and controlled clinical trials comparing PDHA versus usual care/other intervention, as well as qualitative/mixed methods studies dealing with PDHA. Critical appraisal was performed according to the Cochrane risk-of-bias tool in quantitative studies and the Critical Appraisal Skills Programme (CASP) as well as the McMaster University Guidelines for Critical Review Form for qualitative studies and data extraction. Meta-analysis, thematic synthesis and integrative synthesis were performed. Results: EightRCTs (n=1149) and eleven qualitative studies (n=346) met the inclusion criteria. RCTs reported a variety of outcomes (n=17). We are uncertain if PDHA has any effect on patient outcomes in Activities of Daily Living, quality of life, mobility and fear of falling, falls and hospital readmissions (with moderate to very low quality of the evidence). The qualitative studies revealed facilitators and barriers which should be considered by therapists when conducting PDHA. These were related to the following topics: patient safety education, patient information, patients’ acceptance of modifications and aids, functional assessment, standardization of procedures as well as the consideration of relevant patient conditions and contextual factors in PDHA. Conclusion: There is no evidence from the meta-analysis for the effectiveness of PDHA. Further robust studies are needed to adapt and evaluate PDHA interventions, taking the identified stakeholders’ views on PDHA into account and following the current recommendations for the development and evaluation of complex interventions. Trial registration:The review was registered and methods were reported on PROSPERO on 18th July 2018 (https://www.crd.york.ac.uk/PROSPERO. CRD42018100636).
Simulation-based mastery improved nursing skills in BSc Nursing Students: a quasi-experimental study
Authors: Mehdipour-rabori Roghaye , Bagheryan Behnaz , nematollahi monirsadat
Published: December 2020

Background: Clinical education is an essential part of nursing education. Selected clinical teaching methods influence quality of education. Simulation-based mastery learning has been used to improve clinical skills among nursing students and may provide a novel way to enhance nursing skills. This study aimed to assess the effect of the simulation-based mastery learning on the clinical skills of undergraduate nursing students from 2017 to 2019.Methods: This quasi-experimental study was conducted with two groups (the control and intervention). After written consent was received, 105 students were selected by random convenience sampling. The intervention group participated in a simulation-based mastery learning intervention, and the control group received no intervention except for traditional training. The students of both groups completed the demographic information questionnaire and the checklist before and after the intervention. The results were analyzed by SPSS version 21, and descriptive and inferential statistics.Results: The results showed no significant differences between the two groups before the intervention (p> 0.05). In addition, students’ performance in the intervention and control groups improved significantly at the post-test compared with the baseline (p<0.05). Furthermore, Cohen test implied that the simulation-based mastery model used by the intervention group was significantly more effective than the traditional training used by the control.Conclusion: These findings showed that mastery learning was more effective in improving clinical skills in undergraduate nursing students. The results suggest that other nursing and health programs can be developed by implementing mastery-based learning model.
New PTEN mutation identified in a patient with rare bilateral choroidal ganglioneuroma
Authors: Jiang Zhaoxin , Zhang Ting , Chen Chonglin , Sun Limei , Li Songshan , Ding Xiaoyan
Published: December 2020

Background: Choroidal ganglioneuroma is an extremely rare tumor, and there is little knowledge regarding its pathogenesis. We aimed to investigate the phenotypic and genetic alterations in one sporadic patient with a rare case of bilateral choroidal ganglioneuroma. Methods: A 6-year-old boy with histological diagnosis of bilateral ganglioneuroma was recruited for the study. Comprehensive ophthalmic examinations were performed. Genomic DNA was extracted from the peripheral blood samples collected from the patient, his unaffected family members, and 200 unrelated control subjects from the same population. Whole exome sequencing was performed and raw reads were aligned to the human genome reference (hg19) using Burrows-Wheeler Aligner. DNA from all available family members was Sanger sequenced for segregation analysis. Results: Extensive bilateral retinal detachments were observed via optical coherence tomography. Diffuse thickening of choroid was identified with ultrasound B scan and magnetic resonance imaging. Genetic analysis revealed the presence of a novel heterozygous PTEN frameshift mutation, c.498delA (p.Thr167LeufsTer16), in exon 6. It was present in the affected individual, but not in any of the family members. Genetic analysis revealed that there was no mutation in neurofibromatosis-related genes in the family. Upon performing comprehensive systemic examinations, no obvious abnormalities in other organs were observed. Conclusions: A novel de novo PTEN mutation was identified in a patient with bilateral choroidal ganglioneuroma. Although PTEN mutations are known to induce multiple abnormalities, choroidal ganglioneuroma can be the first manifestation without abnormalities in other organs. Further studies are needed to confirm the association between choroidal ganglioneuroma and PTEN mutation.
Impact on Decision Making Framework for Medicine Purchasing in Chinese Public Hospital Decision-making: Determining the Value of Five Dipeptidyl Peptidase 4 (DPP-4) inhibitors
Authors: Bao Yun , Gao Bei , Meng Min , Ge Bin , Yang Yan , Ding Chunchun , Shi Bingyin , Tian Limin
Published: December 2020

Background: Medicine purchasing in Chinese public hospitals is decided by the hospital Pharmacy Management Committee (PMC), that is complex, subjective and requires efficient methods to ensure transparency and consistency for the factors being considered. This study aimed to use the Evidence and Value: Impact on Decision Making (EVIDEM) framework to assess medicine in these hospitals. In this study anti-diabetic drugs DPP-4 inhibitors, which work by inhibiting the activation of the Dipeptidyl Peptidase 4 (DPP-4) inhibitors, were appraised.Methods: Following EVIDEM methodology, we convened an appraisal group and asked each individual to express their perspectives by assigning weights to each criterion. A systematic literature search for information of each criterion of five DPP-4 inhibitors was completed. Then the appraisal group scored for each criterion of the five DPP-4 inhibitors. The estimated value of the five DPP-4 inhibitors was obtained by Multi-Criteria Decision Analysis (MCDA) which combined individual weighting of each criterion with individual scoring for each intervention in each criterion. Results: By assigning weights, the most important criterion was the quality of evidence (4.01±0.52), and that the comparative cost consequences-non-medical cost had lowest weight (2.87±1.03). Criteria included disease severity, size of the affected population, comparative effectiveness, type of therapeutic/preventive benefit and cost of intervention, all of which were assigned the same weight of 3.58. After MCDA, the overall value orders for each DPP-4 inhibitor included Sitagliptin (0.45), Linagliptin (0.44), Vildagliptin (0.43), Alogliptin (0.42) and Saxagliptin (0.40). Conclusions: Based on EVIDEM framework and MCDA, we found that overall value of five DPP-4 inhibitors was similar. it is feasible to use the EVIDEM framework and MCDA in purchasing medicine for Chinese public hospitals.
Distinct mutation profiles between primary bladder cancer and circulating tumor cells warrant the use of circulating tumors cells as cellular resource for mutation follow-up
Authors: Tae-Min Kim , Yoo Jinseon , Moon Hyong Woo , Hur Kyung jae , Choi Jin Bong , Hong Sung-Hoo , Lee Ji Youl , Ha U-Syn
Published: December 2020

Background: While circulating tumor cells may serve as minimally invasive cancer markers for bladder cancers, the relationship between primary bladder cancers and circulating tumor cells in terms of somatic mutations is largely unknown. Genome sequencing of bladder tumor and circulating tumor cells is highlighted to identify the somatic mutations of primary bladder cancer.Methods: Bladder cancer tissue was collected by transurethral resection of the bladder and preserved by snap-freezing. Circulating tumor cells were Isolated from the blood obtained before treatment. We performed whole exome sequencing of 20 matched pairs of primary bladder cancers and circulating tumor cells to identify and compare somatic mutations of these two different genomic resources.Results: We observed that mutation abundances of primary bladder cancers and circulating tumor cells were highly variable. The mutation abundance was not significantly correlated between matched pairs. Of note, the mutation concordance between two resources was only 3 – 24% across 20 pairs examined, suggesting that the circulating tumor cell genomes of bladder cancer patients might be genetically distinct from primary bladder cancers. A relative enrichment of mutations belonging to APOBEC-related signature and a depletion of C-to-G transversions were observed for primary- and circulating tumor cells specific mutations, respectively, suggesting that distinct mutation forces might have been operative in respective lesions during carcinogenesis. Conclusions: The observed discrepancy of mutation abundance and low concordance level of mutations between genomes of primary bladder cancers and circulating tumor cells should be taken into account when evaluating clinical utility of circulating tumor cells for treatments and follow-up of bladder cancers.Trial registration: Patients were selected and registered retrospectively, and medical records were evaluated.
Efficacy of contrast-enhanced ultrasonography and shear-wave elastography in conjunction with BI-RADS classification for diagnosis of small breast nodules
Authors: Shen Yan , He Jie , Liu Miao , Hu Jiaojiao , Wan Yonglin , Zhang Tingting , Ding Jun , Dong Jiangnan , Fu Xiaohong
Published: December 2020

Background: Identification of malignancy in small breast nodules can be difficult using conventional methods, especially in patients with dense breast tissue. Advanced imaging techniques, including contrast-enhanced ultrasound (CEUS) and shear-wave elastography (SWE), could be used in conjunction with Breast Imaging Reporting and Data System (BI-RADS) classification to characterize these nodules more effectively. This study aimed to evaluate the use of CEUS and SWE for the differentiation of benign and malignant small breast nodules (maximum diameter ≤ 2 cm).Methods: This retrospective study reviewed the imaging data of 302 patients who underwent evaluation for 305 small breast nodules from November 2015 to December 2019. BI-RADS classification of nodules and the results of CEUS and SWE were retrospectively analyzed; the diagnostic efficacy of these techniques was evaluated by comparison with pathology results. Receiver operating characteristic curves were analyzed based on the CEUS patterns and shear-wave velocity values of nodules. The sensitivities, specificities, positive and negative predictive values, and accuracies of BI-RADS, CEUS, SWE, and a combination of all three methods for identifying benign versus malignant small breast nodules were investigated.Results: CEUS was effective in diagnosing malignant nodules when at least two of the nine suspicious features were present. Receiver operating curve analysis revealed that the best cut-off value for SWE was 3.7 m/s. For the diagnosis of benign breast nodules, the BI-RADS classification was reduced by one level when both CEUS and SWE data were used, and was unchanged when CEUS or SWE alone was used; the highest and lowest levels were category 5 and 3, respectively. Furthermore, when using the combined method, 75.8% (91/120) of small breast nodules with a BI-RADS category 4A did not need coarse needle biopsies.Conclusion: Both CEUS and SWE can be used as auxiliary methods for clarifying BI-RADS classification of breast nodules, and a combination of these techniques may provide improved diagnostic efficacy for identifying malignancy in small breast nodules.
SMAD4 haploinsufficiency in small intestinal neuroendocrine tumors
Authors: Hofving Tobias , Elias Erik , Rehammar Anna , Inge Linda , Altiparmak Gülay , Persson Marta , Kristiansson Erik , Johansson Martin E , Nilsson Ola , Arvidsson Yvonne
Published: December 2020

Background Patients with small intestinal neuroendocrine tumors (SINETs) frequently present with lymph node and liver metastases at the time of diagnosis, but the molecular changes that lead to the progression of these tumors are largely unknown. Sequencing studies have only identified recurrent point mutations at low frequencies with CDKN1B being the most common harboring heterozygous mutations in less than 10% of all tumors. Although SINETs are genetically stable tumors with a low frequency of point mutations and indels, they often harbor recurrent hemizygous copy number alterations (CNAs) yet the functional implications of these CNA are unclear.MethodsUtilizing comparative genomic hybridization (CGH) arrays we analyzed the CNA profile of 131 SINETs from 117 patients. Two tumor suppressor genes and corresponding proteins i.e. SMAD4, and CDKN1B, were further characterized using a tissue microarray (TMA) with 846 SINETs. Immunohistochemistry (IHC) was used to quantify protein expression in TMA samples and this was correlated with chromosome number evaluated with fluorescent in-situ hybridization (FISH). Intestinal tissue from a Smad4+/- mouse model was used to detect entero-endocrine cell hyperplasia with IHC.ResultsAnalyzing the CGH arrays we found loss of chromosome 18q and SMAD4 in 71% of SINETs and that focal loss of chromosome 12 affecting the CDKN1B was present in 9.4% of SINETs. No homozygous loss of chromosome 18 was detected. Hemizygous loss of SMAD4, but not CDKN1B, significantly correlated with reduced protein levels but hemizygous loss of SMAD4 did not induce entero-endocrine cell hyperplasia in the Smad4+/- mouse model. In addition, patients with low SMAD4 protein expression in primary tumors more often presented with metastatic disease.Conclusions Hemizygous loss of chromosome 18q and the SMAD4 gene is the most common genetic event in SINETs and our results suggests that this could influence SMAD4 protein expression and spread of metastases. Although SMAD4 haploinsufficiency alone did not induce tumor initiation, loss of chromosome 18 could represent an evolutionary advantage in SINETs explaining the high prevalence of this aberration. Functional consequences of reduced SMAD4 protein levels could hypothetically be a potential mechanism as to why loss of chromosome 18 appears to be clonally selected in SINETs.
Predictors of adherence to prescribed exercise programs for older adults with non-musculoskeletal indications for exercise: a systematic review
Authors: Shaw Julia F , Pilon Sophie , Vierula Matthieu , McIsaac Daniel I
Published: December 2020

BACKGROUND AND OBJECTIVES: Prescribed exercise to treat medical conditions and to prepare for surgery is a promising intervention to prevent adverse health outcomes for older adults; however, adherence to exercise programs may be low. Our objective was to identify and grade the quality of predictors of adherence to prescribed exercise in older adults.METHODS: After registration (CRD42018108242), prospective experimental studies were identified using a peer-reviewed search strategy applied to MEDLINE, EMBASE, Cochrane and CINAHL from inception until April 23, 2019. Following independent and duplicate review of titles, abstracts and full texts, we included prospective studies with an average population age >65 years, where exercise was formally prescribed for a medical or surgical condition. We excluded studies where exercise was prescribed for a chronic musculoskeletal condition. Risk of bias was assessed using the Quality in Prognostic studies tool or Cochrane risk of bias tool, as appropriate. Predictors of adherence were identified, pooled, and graded for quality using an adaptation of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework for predictor studies.RESULTS: We included 19 observational studies and 4 randomized controlled trials (n=5785) Indications for exercise included cardiac (n=6), pulmonary rehabilitation (n=7), or other (n=10; surgical, medical, and neurologic). Overall adherence rate was reported in 20 studies (range 21%-93%; mean 68%, standard deviation 23%). Moderate-quality evidence suggested that positive predictors of adherence were self-efficacy and good self-rated mental health; negative predictors were depression (high quality) and distance from the exercise facility. Moderate-quality evidence suggested that comorbidity and age were not predictive of adherence.CONCLUSIONS: These findings can inform design of future exercise programs as well as identification of individuals who may require extra support to benefit from prescribed exercise.
Two-year outcomes after full-thickness astigmatic keratotomy combined with small-incision lenticule extraction for high astigmatism
Authors: Kim Bu Ki , Chung Young Taek
Published: December 2020

Background: To evaluate clinical outcomes after full-thickness astigmatic keratotomy (FTAK) combined with small-incision lenticule extraction (SMILE) in eyes with high astigmatism.Methods: This study comprised 75 eyes of 43 patients with over 4.0 diopters (D) of astigmatism who were treated with SMILE after FTAK. Visual acuities and refractive measurements were evaluated at 1 month after FTAK, and 1, 6, 12, and 24 months after SMILE. Vector analysis of the astigmatic changes was performed using the Alpins method.Results: Twenty-four months after the combined procedure, the average spherical equivalent was reduced from -6.56 ± 2.38 D to -0.36 ± 0.42 D (p < 0.001). The uncorrected and corrected distance visual acuities improved from 1.54 ± 5.53 to -0.02 ± 0.09 and from -0.03 ± 0.07 D to -0.07 ± 0.08 D (both p < 0.001), respectively. The preoperative mean astigmatism was -5.48 ± 1.17 D, which was reduced to -2.27 ± 0.97 D and -0.34 ± 0.26 D at 1 month after FTAK and 24 months after SMILE, respectively (p <0.001). The surgically-induced astigmatism after FTAK, SMILE, and FTAK and SMILE combined was 3.38 ± 1.18 D, 2.22 ± 0.84 D, and 5.39 ± 1.20 D, respectively. Furthermore, the correction index of FTAK, SMILE, and FTAK and SMILE combined was 0.63 ± 0.17, 0.90 ± 0.40, and 0.98 ± 0.06, respectively. There were no intraoperative or postoperative complications.Conclusion: Our surgical procedure combining FTAK and SMILE showed good and stable clinical outcomes during two-year follow-up for the treatment of high astigmatism.
Does admission prevalence change after reconfiguration of inpatient services? An interrupted time series analysis of the impact of reconfiguration in five centres
Authors: Turner Steve , Martin Joanne , Raja Edwin Amalraj
Published: December 2020

Background. Service reconfiguration of inpatient services in a hospital includes complete and partial closure of all emergency inpatient facilities. The “natural experiment” of service reconfiguration may give insight into drivers for emergency admissions to hospital. This study addressed the question does the prevalence of emergency admission to hospital for children change after reconfiguration of inpatient services?Methods. There were five service reconfigurations in Scottish hospitals between 2004 and 2018 where emergency admissions to one “reconfigured” hospital were halted (permanently or temporarily) and directed to a second “adjacent” hospital. The number of emergency admissions (standardised to /1000 children in the regional population) per month to the “reconfigured” and “adjacent” hospitals was obtained for five years prior to reconfiguration and up to five years afterwards. An interrupted time series analysis considered the association between reconfiguration and admissions across pairs comprised of “reconfigured” and “adjacent” hospitals, with adjustment for seasonality and an overall rising trend in admissions.Results. Of the five episodes of reconfiguration, two were immediate closure, two involved closure only to overnight admissions and one with overnight closure for a period and then closure. In “reconfigured” hospitals there was an average fall of 117 admissions/month [95% CI 78, 156] in the year after reconfiguration compared to the year before, and in “adjacent” hospitals admissions rose by 82/month [32, 131]. Across paired reconfigured and adjacent hospitals, in the months post reconfiguration, the overall number of admissions to one hospital pair slowed, in another pair admissions accelerated, and admission prevalence was unchanged in three pairs. After reconfiguration in one hospital, there was a rise in admissions to a third hospital which was closer than the named “adjacent” hospital. Conclusions. There are diverse outcomes for the number of emergency admissions post reconfiguration of inpatient facilities. Factors including resources placed in the community after local reconfiguration, distance to the “adjacent” hospital and local deprivation may be important drivers for admission pathways after reconfiguration. Policy makers considering reconfiguration might consider a number of factors which may be important determinants of admissions post reconfiguration.
Alternative Polyadenylation in Response to Temperature Stress Contributes to Gene Regulation in Populus trichocarpa
Authors: Yan Chao , Wang Yupeng , Lyu Tao , Hu Zhikang , Ye Ning , Liu Weixin , Li Jiyuan , Yao Xiaohua , Yin Hengfu
Published: December 2020

Background: Genome-wide change of polyadenylation (polyA) sites (also known as alternative polyadenylation, APA) is emerging as an important strategy of gene regulation in response to stress in plants. But little is known in woody perennials that are persistently dealing with multiple abiotic stresses. Results: Here, we performed a genome-wide profiling of polyadenylation sites under heat and cold treatments in Populus trichocarpa. Through a comprehensive analysis of polyA tail sequences, we identified 25,919 polyA-site clusters (PACs), and revealed 3429 and 3139 genes shifted polyA sites under heat and cold stresses respectively. We found that a small proportion of genes possessed APA that affected the open reading frames; and some shifts were commonly identified. Functional analysis of genes displaying shifted polyA tails suggested that pathways related to RNA metabolism were linked to regulate the APA events under both heat and cold stresses. Interestingly, we found that the heat stress induced a significantly more antisense PACs comparing to cold and control conditions. Furthermore, we showed that a unique cis-element (AAAAAA) was predominately enriched downstream of PACs in P. trichocarpa genes; and this sequence signal was only absent in shifted PACs under the heat condition, indicating a distinct APA mechanism responsive to heat tolerance. Conclusions: This work provides a comprehensive picture of global polyadenylation patterns in response to temperatures stresses in trees. We show that the frequent change of polyA tail is a potential mechanism of gene regulation responsive to stress, which are associated with distinctive sequence signatures.
Resilience and sense of coherence in first year medical students - a cross-sectional study
Authors: Luibl Lena , Traversari Julia , Paulsen Friedrich , Scholz Michael , Burger Pascal
Published: December 2020

Background: A broad range of studies show that medical students often have a significantly deteriorated mental health status. Although starting medical school with values comparable to the population average, only a few semesters later, medical undergraduates show increased rates of psychological risk states and some manifest mental illnesses, such as burnout and depression. In our survey we intentionally assessed mental health parameters from a salutogenetic, i.e. resource-oriented point of view. Methods: We examined first-year medical students in a cross-sectional study and assessed sense of coherence (SOC) and resilience as parameters from the salutogenesis model by Antonovsky in a structured way using validated, self-administered questionnaires. In total, we examined 236 students of human medicine, dentistry and molecular medicine at the Friedrich-Alexander-University Erlangen-Nürnberg (FAU).Results: Our analyses showed significantly higher values of resilience among male students compared to female students. In contrast, even though a significant correlation between resilience and SOC was observed, only a non-significantly lower value of SOC was found in female students. Compared to the population average our medical students in their first year of study showed significantly lower values for resilience and SOC. Conclusion: Resilience and SOC are known to correlate with psychological stress (burnout parameters) and depression. In order to keep protective factors like SOC and resilience in medical students at a good and healthy level we see the necessity to address that problem proactively and educationally. Integrating training focused on the preservation of the students´ own mental health into the medical curriculum from the beginning of university courses, and throughout the whole medical study course, is essential and should be an obligatory training goal. Based on our study results, we also deem it necessary to think about ways to adapt the measures for the gender-specific needs of our students, e.g. dependent on their biological gender.
Early macrophage infiltrates impair pancreatic cancer cell growth by TNF-α secretion
Authors: Tekin Cansu , Aberson Hella L , Bijlsma Maarten F , Spek C. Arnold
Published: December 2020

Background: Pancreatic ductal adenocarcinoma (PDAC) is a grim disease with high mortality rates. Increased macrophage influx in PDAC is a common hallmark and associated with poor prognosis. Macrophages have high cellular plasticity, which can differentiate into both anti- and pro-tumorigenic properties. Here, we investigated how naïve (M0) macrophages differ from other macrophages in their anti-tumorigenic activities.Methods: In vitro BrdU proliferation and Annexin V cell death analyses were performed on PANC-1 and MIA PaCa-2 PDAC cell lines exposed to conditioned medium of different macrophage subsets. Macrophage secreted factors were measured by transcript analysis and ELISA. Therapeutic antibodies were used to functionally establish the impact of the identified cytokine on PDAC proliferation.Results: Proliferation and cell death assays revealed that only M0 macrophages harbor anti-tumorigenic activities and that M1, M2, and TAMs do not. mRNA analysis and ELISA results suggested TNF-α as a potential candidate to mediate M macrophage induced cell death. To demonstrate the importance of TNF-α in M macrophage-induced cell death, PANC-1 and MIA PaCa-2 cell-lines were exposed to M macrophage conditioned medium in the presence of the TNF-α inhibitor Infliximab, which effectively diminished the anti-tumor activities of M0 macrophages.Conclusion: Newly tumor-infiltrated naive M0 macrophages exert anti-tumorigenic activities via TNF-α secretion. Their subsequent differentiation into either M1, M2, or TAM subsets reduces TNF-α levels, thereby abolishing their cytotoxic activity on PDAC cells. These data suggest that reestablishing TNF-α secretion in differentiated macrophages might yield a therapeutic benefit.
Anatomy Education Environment Measurement Inventory (AEEMI): A cross-validation study in Malaysian medical schools
Authors: Hadie Siti Nurma Hanim , Yusoff Muhamad Saiful Bahri , Arifin Wan Nor , Kasim Fazlina , Ismail Zul Izhar Mohd , Asari Mohd Anizam , Sulong Husnaida Manan @ , Hassan Asma' , Muda Tg Fatimah Murniwati Tg , Bakar Yasrul Izad Abu , Zamin Rasheeda Mohd , Ramli Elvy Suhana Mohd , Hod Rafidah , Talip Saiful Bahri , Noor Ku Mastura Ku Mohd , Merican Yusoff Sharizal Yusoff Azmi , Azmi Muhammad Fairuz , Latiff Atikah Abdul , Rushaidhi Madihah
Published: December 2020

Background: The Anatomy Education Environment Measurement Inventory (AEEMI) evaluates the perception of medical students of educational climates with regard to teaching and learning anatomy. The study aimed to cross-validate the AEEMI, which was previously studied in a public medical school, and proposed a valid universal model of AEEMI across public and private medical schools in Malaysia. Methods: The initial 11-factor and 132-item AEEMI was distributed to 1,930 pre-clinical and clinical year medical students from 11 medical schools in Malaysia. The study examined the construct validity of the AEEMI using exploratory and confirmatory factor analyses. Results: The best-fit model of AEEMI was achieved using 5 factors and 26 items (χ 2 = 3300.71 (df = 1680), P < 0.001, χ 2/df = 1.965, Root Mean Square of Error Approximation (RMSEA) = 0.018, Goodness-of-fit Index (GFI) = 0.929, Comparative Fit Index (CFI) = 0.962, Normed Fit Index (NFI) = 0.927, Tucker–Lewis Index (TLI) = 0.956) with Cronbach’s alpha values ranging from 0.621 to 0.927. Findings of the cross-validation across institutions and phases of medical training indicated that the AEEMI measures nearly the same constructs as the previously validated version with several modifications to the item placement within each factor. Conclusions: These results confirmed that variability exists within factors of the anatomy education environment among institutions. Hence, with modifications to the internal structure, the proposed model of the AEEMI can be considered universally applicable in the Malaysian context and thus can be used as one of the tools for auditing and benchmarking the anatomy curriculum.
Ocular abnormalities in a large patient cohort with Retinitis Pigmentosa in Western China
Authors: Tan Lian , Long Yanling , Li Ziyang , Ying Xi , Ren Jiayun , Sun Cheng , Meng Xiaohong , Li Shiying
Published: December 2020

Background To report the prevalence of ocular abnormalities and investigate visual acuity in a large cohort of retinitis pigmentosa (RP) patients in Western China.
Methods The medical records and ophthalmic examination reports of 2127 eyes of 1065 RP patients at one eye hospital were retrospectively reviewed to determined the prevalence of ocular abnormalities and the relationship between best corrected visual acuity (BCVA) and macular abnormalities.
Results Nyctalopia (58.2%) and blurred vision (27.1%) were the leading reasons for RP patients to request an ophthalmic examination. BCVA measurements in the better eyes at first clinical presentation showed that 304 patients (28.5%) were categorised as blind and 220 patients (20.7%) as low vision. The most common ocular abnormalities were macular abnormalities (59.7%) and cataracts (43.1%). The macular abnormalities included epiretinal membranes (51.1%), cystoid macular edema (18.4%), vitreomacular traction syndrome (2.4%), macular holes (2.3%) and choroidal neovascular membranes (0.05%). Glaucoma was found in 35 eyes (1.6%). The proportions of epiretinal membranes ( p =0.001) and macular holes ( p =0.008) increased significantly with age. Cystoid macular edema was significantly associated with poorer visual acuity in RP patients with clear lens ( p =0.002).
Conclusion Cataracts and macular abnormalities are common in RP patients. Of the macular abnormalities, cystoid macular edema may have a negative effect on BCVA in RP patients with clear lens. Therefore, optical coherence tomography screening in RP patients is highly recommended for early detection and treatment of maculopathy.
Experience and practice of the Emergency Operations Center, Chinese Center for Disease Control and Prevention: a case study of response to the H7N9 outbreak
Authors: DING FAN , Li Qun , Jin Lianmei
Published: December 2020

Background: Emergency Operations Center (EOC) is a place to provide response to public health emergencies. Chinese Center for Disease Control and Prevention (China CDC)’s EOC was officially established in 2016, which has been the core department for the public health emergencies and risk response. In recent years, we have been continuously improving the function of EOC through many incidents. In the study, we hope to share the construction status, operation management experience and the response process in the H7N9 outbreak.Main text: The China CDC’s EOC mainly focus on building the five core elements including sites/places and facilities, information and data, plans and procedures, training and exercises, and logistics. Based on summarizing previous emergency response, the China CDC’s EOC established its own incident management and the standardized response procedures. The event-specific data, context-specific data and event management data could be obtained through various source.. The logistics department of the EOC also provides comprehensive support. And that the well-trained staff is another necessary conditions for its operation. Through sharing the response process of H7N9 outbreak, it further explains the EOC’s functions in the five phases of outbreak response, such as the formulation of the incident response framework, monitoring, personnel dispatch and resource mobilization.Conclusions: The EOC contributes to faster and more efficient responses during emergencies which enable a greater reduction in morbidity and mortality. Compared with the traditional incident response process, under the command and coordination of China CDC’s EOC, each group involved in the response has a clearer goal, responsibilities and tasks at each stage. Meanwhile, each group also gave full play to its own expertise and advantages. As a whole, incident response tended to be more specialized and precise, which generally improves the efficiency of incident response. However, different countries and regions have different response processes to the events. We still suggested that appropriate emergency operation plan should be made according to the complexity of incident response in the region when constructing response mechanism, through our experience. And the China CDC’s EOC is still at growing and groping phase.
The ‘GROW Social Network’ datasets
Authors: Gesell Sabina B. , Sommer Evan C. , Barkin Shari l.
Published: December 2020

The GROW Social Network datasets were compiled as part of a 3-year community-based family-based pediatric obesity prevention intervention (N = 610). The datasets include (i) multiplex edges between adult study participants at four timepoints (baseline, 3, 12, and 36 mon), and (ii) multiplex edges within small intervention-only subgroups (30 groups of approximately 10 adult intervention participants) and a previously validated self-report measure of perceived cohesion at three timepoints (3, 6, and 12 wk). Actor attributes are richly characterized in a linkable dataset.