bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-dose carbon-ion based radiotherapy of primary and recurrent sacrococcygeal chordomas: Long-term clinical results of a single particle therapy center.
Authors: Bostel Tilman , Mattke Matthias , Nicolay Nils Henrik , Welzel Thomas , Wollschläger Daniel , Akbaba Sati , Mayer Arnulf , Sprave Tanja , Debus Jürgen , Uhl Matthias 
Published: August 2020

Abstract
BackgroundThis study aimed to analyze the oncological long-term results and late toxicity of carbon ion-based radiotherapy (RT) of patients with sacral chordoma and to identify potential prognostic factors for local control (LC) and overall survival (OS).MethodsA total of 68 patients with sacral chordoma treated at the Heidelberg Ion Beam Therapy Center were included in this study. Of these 52 patients (77%) received a primary RT and 16 patients (23%) received a RT in a recurrent situation. All patients were treated with carbon ion RT (CIRT), either in combination with photons (n = 22; 32%) or as a monotherapy (n = 46; 68%), with a median radiation dose of 66 Gy RBE (range 60 - 74 Gy). In 40 patients (59%), RT was performed in the postoperative situation. Postoperative care included regular MRI scans. Local progression was defined as an enlargement of the maximum tumor diameter by 10% or a new tumor growth within the planning target volume (PTV). LC and OS were determined using the Kaplan-Meier method. Furthermore, the relevance of various prognostic factors for LC and OS was assessed by univariate and multivariate analysis.ResultsThe median follow-up period was 60 months (range 1.3 – 97.4 months). The 5-year rates for LC, progression-free survival, metastasis-free survival and OS were 53%, 53%, 52% and 74%, respectively. Local recurrence was observed in 31 patients (46%), occurring after a median follow-up time of 25 months (range 2.5 – 73.1months). Only 10% of local recurrences occurred later than 5 years after RT. Statistical analysis showed thatRT in the relapse situation corresponded to inferior LC rates compared to the primary situation, while other factors such as the GTV, radiation dose (EQD2) and treatment approach (CIRT alone vs. CIRT combined with photons) were insignificant. For OS after RT, patient age and PTV size proved to be significant predictors.The incidence of late toxicity ≥ III° according to CTCAE v5.0 was 21%. Sacral insufficiency fractures occurred in 49% of patients (maximum III°: 16%) and were thus by far the most frequent late side effect in our analysis. Radiogenic damage to the peripheral nerves, intestinal tract and skin was observed in only 9% (≥ III°: 5%), 3% (all II°) and 9% (all I°) of patients.ConclusionOur analysis showed only moderate long-term LC rates after carbon ion-based RT, with sacral chordomas having a particularly poor prognosis in the recurrent situation. Therefore, future studies should evaluate the safety and effectiveness of further dose escalation and hypofractionation of RT in sacral chordoma and weight potential benefits of dose escalation against side effects.
Use of Monitoring Indicators in Hospital Management of Antimicrobials
Authors: Silva Ravena , Silva Ravena , Mendonça Simonize , Leão Ingrid , Santos Quesia , Batista Alessandra , Melo Matheus , Xavier Milena , Júnior Lucindo Quintans , Silva Wellington da , Lobo Iza Maria Fraga 
Published: August 2020

Abstract
Background: It is described in the literature that between 25% to 50% of antimicrobial prescriptions, in the hospital environment, are unnecessary or inadequate, directly impacting antimicrobial resistance. The National Health Surveillance Agency launched the “Brazil Stewardship Project” to assess the national panorama of antimicrobial use management programs, therefore, it is expected that managers will be encouraged to implement the antimicrobial use management program, with the publication of the results, enabling the comparison of national data. In this context, measures and indicators of antimicrobial use will be particularly important. We demonstrate the application of the indicators DOT, LOT e DOT/LOT ratio to explore and monitor antimicrobials use. Methods: This is an observational, analytical and prospective study conducted in a teaching hospital, with 94 active beds, distributed between the intensive care unit (ICU), the surgical clinic (SUR), the medical clinic (MED), the pneumology/infectology (PNE/INF) and pediatrics (PED). Results: During the study period, a total of 11,634 patient-days were followed up and an average of 50.4% of patients were exposed to some antimicrobial, showing significant reduction throughout the year. In 376 days, for every 1,000 days of hospitalization, patients were receiving antimicrobial therapy (LOT = 376/1000pd). Overall, the 1st generation cephalosporins and fluoroquinolones were highlighted both in the number of prescriptions and in the duration of therapy. The calculated global DOT / LOT ratio showed that each patient received an average of 1.5 antimicrobials during the hospital stay. The incidence of antimicrobial resistance, globally, for both Methicillin R and Carbapenem R , was 1 per 1000 patient-days. Conclusions: The indicators addressed in this study proved to be of great relevance for obtaining data regarding the use of antimicrobials, contributing to the initiatives to be taken by the Stewardship program. This study is expected to encourage other hospitals to monitor the use of antimicrobials, allowing comparison of data.
Investigation of the genetic variation in ACE2 on the structural recognition by the novel coronavirus (SARS-CoV-2)
Authors: Guo Xingyi , Chen Zhishan , Xia Yumin , Lin Weiqiang , Li Hongzhi 
Published: August 2020

Abstract
Background: The outbreak of coronavirus disease (COVID-19) was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), through its surface spike glycoprotein (S-protein) recognition on the receptor Angiotensin-converting enzyme 2 (ACE2) in humans. However, it remains unclear how genetic variations in ACE2 may affect its function and structure, and consequently alter the recognition by SARS-CoV-2. Methods: We have systemically characterized missense variants in the gene ACE2 using data from the Genome Aggregation Database (gnomAD; N = 141,456). To investigate the putative deleterious role of missense variants, six existing functional prediction tools were applied to evaluate their impact. We further analyzed the structural flexibility of ACE2 and its protein-protein interface with the S-protein of SARS-CoV-2 using our developed Legion Interfaces Analysis (LiAn) program.Results: Here, we characterized a total of 12 ACE2 putative deleterious missense variants. Of those 12 variants, we further showed that p.His378Arg could directly weaken the binding of catalytic metal atom to decrease ACE2 activity and p.Ser19Pro could distort the most important helix to the S-protein. Another seven missense variants may affect secondary structures (i.e. p.Gly211Arg; p.Asp206Gly; p.Arg219Cys; p.Arg219His, p.Lys341Arg, p.Ile468Val, and p.Ser547Cys), whereas p.Ile468Val with AF = 0.01 is only present in Asian.Conclusions: We provide strong evidence of putative deleterious missense variants in ACE2 that are present in specific populations, which could disrupt the function and structure of ACE2. These findings provide novel insight into the genetic variation in ACE2 which may affect the SARS-CoV-2 recognition and infection, and COVID-19 susceptibility and treatment.
Insights on mental health when living with r/Rheumatoid r/Thritis: A descriptive qualitative study of Reddit threads
Authors: Park Jamie Yea Eun , Howren Alyssa M. , Davidson Eileen , De Vera Mary A 
Published: August 2020

Abstract
Background: Online forums, where individuals ask questions, discuss opinions and share experiences provide a valuable pool of publicly available data to better understand impacts of disease and associated complications. Reddit is a highly visited social news and discussion website where individuals anonymously ask questions, post opinions and share experiences, which provide a valuable pool of publicly available data. Our objective was to systematically search and analyze threads on the social news website, Reddit, to understand experiences of individuals with rheumatoid arthritis (RA) regarding their mental health. Methods: We conducted a patient-oriented descriptive qualitative study. We identified threads from two subreddits, “r/Thritis” and “r/Rheumatoid”, using keywords such as “mood”, “mental health”, “stressed”, “depressed”, “anxious” over a 1-year period between June 2018 and June 2019. For included threads, we extracted the title, original post, and corresponding comments and responses. We applied thematic analysis using an inductive approach. Results: Of 81 threads identified, we included 27. We identified four themes: 1) Navigating the management of RA explores how the physical impacts of the disease, lack of health resources/support and the complexity of medications affect mental health; 2) Experiencing impact on relationships and social isolation includes experiencing misconceptions of RA, feeling misunderstood and feeling guilt; 3) Experiencing loss, touches on the helplessness brought by challenges with performing self-defining activities such as self-care, work, and childbearing/parenting; and finally, 4) Experiencing emotional struggles captures how tension between fighting through and despair has led some to suicide ideation and thoughts of death.Conclusions: Online forums and communities such as Reddit have created opportunities for individuals with RA to share experiences on mental health matters, which they may not necessarily be able to share with others.
­­­­­The kappa opioid receptor agonist U50,488H did not affect brain-stimulation reward while it elicited conditioned place aversion in mice
Authors: Huang Peng , Gentile Taylor , Muschamp John , Liu-Chen Lee-Yuan 
Published: August 2020

Abstract
Objective: Selective kappa opioid receptor (KOR) agonists were shown to produce a dose-dependent depression of brain-stimulation reward (BSR) in the rat intracranial self-stimulation (ICSS) tests. However, limited studies using mice produced less conclusive results. Here the effects of U50,488H were re-examined on BSR in mice with a larger cohort of animals. Results: Forty C57BL/6J male mice were implanted with the electrodes in medial forebrain bundle. About a week after surgery, mice were subject to ICSS training. Only eighteen passed the two-phase procedures, at which point they readily spun the wheels to obtain reinforcing effect of BSR, and were used for the ICSS tests. Compared with saline (s.c.), U50,488H (2 mg/kg, s.c.) did not have effects on the BSR thresholds within 1 h post-treatment, while it decreased the maximum wheel-spinning rates in a time-dependent manner. In contrast, cocaine (5 mg/kg, s.c.) decreased the BSR thresholds time-dependently without affecting the maximum wheel-spinning rates in the same cohort of mice, demonstrating the validity of our mouse ICSS models. For comparison, U50,488H (2 mg/kg, s.c.) induced significant conditioned place aversion (CPA) in a different cohort of mice without surgeries. Thus, ICSS may not be an appropriate test for KOR agonist-induced aversion in mice.
Patients and relatives as auditors of safe practices in oncology and hematology day hospitals
Authors: Rodrigo-Rincon Maria Isabel , Aristorena Isabel Irigoyen , Tirapu-Leon Belén , Barcala Nicolas Zaballos , Carricas Maite Sarobe , Lobo-Palanco Joaquin , Caamaño Maria Luisa Antelo , Martin-Vizcaino Marta , Burnett Susan 
Published: August 2020

Abstract
Background: When there is a gap in professionals’ adherence to safe practices during cancer treatment, the consequences can be serious. Identifying these gaps in order to enable improvements in patient safety can be a challenge. This study aimed to assess if cancer patients and their relatives can be given the skills to audit four safe practices reliably, and to explore whether they are willing to play this new role. Methods: We recruited 136 participants in 2018, from the oncology and haematology day hospital of a tertiary hospital in Spain. Patient identification, hand hygiene, blood or chemotherapy identification, and secondary effects related to transfusion and chemotherapy, were the safe practices selected for evaluation. The study comprised two parts: an interventional educational program and a cross-sectional design to collect data and assess to what degree participants are able to be auditors and are willing to be auditors depending on their characteristics using multivariate logistic regression models. A participant’s auditing skill was assessed pre and post the educational intervention.Results: The model was seeking predictors of being a good auditor and 63 participants (46.3%) were classified as good auditors after the training. To have lower age, to have higher educational level and to have had experience a previous adverse event were associated with a higher probability of being good auditors. Additionally, 106 (77.9%) participants said that they would like to anonymously audit the professionals’ compliance of at least three of four safe practices. The willingness to audit safe practices was differed depending on the safe practice but these differences did not reach statistical significance. Conclusions: The data gathered by patients and relatives acting as auditors can provide healthcare organizations with valuable information about safety and quality of care that is not accessible otherwise. This new role provides an innovative way to engage patients and their families’ in healthcare safety where other methods have not had success. The paper sets out the methods that healthcare organizations need to undertake to enrol and train patients and relatives in an auditor role.
Effect of Vitamin D Intervention and outdoor activity on serum 25-Hydroxyvitamin D among children in North China: an observational study
Authors: Zhang Xuguang , Chen Yanping , Jin Shanshan , Bi Xinxin , Chen Dongkai , Zhang Dongmei , Liu Li , Jing Hong , Na Lixin 
Published: August 2020

Abstract
Background: Living at high latitudes is one of the risk factors for vitamin D deficiency in children. However, evidence on vitamin D improvement for this pediatric population to date is limited. This study aims at evaluating the effect of different vitamin D intervention methods and outdoor activity on the vitamin D status of children in North China. Methods: A total of 55,925 children aged 1 month to 18 years old were recruited from pediatric outpatient departments from July 2016 to June 2017. Data on demographics, anthropometric measurements, vitamin D intervention, and outdoor activity were recorded. The serum levels of 25-hydroxycholecalciferol (25(OH)D) were determined by high performance liquid chromatography tandem–mass spectrometry. Logistic regression analysis was performed to assess the association of vitamin D intervention or outdoor activity with blood vitamin D status, adjusted for age, gender, BMI for age, and seasons.Results: The overall rate of hypovitaminosis D was 65.60%. Of the children’s outdoor activity, 35.63%, 31.95%, and 32.42% were below 30min/d, 30-60 min/d and over 60min/d, respectively. Furthermore, the proportion of therapeutic intervention, supplementation intervention and no vitamin D intervention among the children was 16.48%, 32.87%, and 50.65%, respectively. After adjusted for confounding factors, vitamin D intervention was associated with a lower risk of hypovitaminosis D, with OR (95% CI) of 0.191 (0.180, 0.202) in children with therapeutic doses and 0.423 (0.404, 0.443) in those with supplementation doses, compared with children without vitamin D intervention. In addition, longer outdoor time was associated with a lower risk of hypovitaminosis D [0.479 (0.456, 0.504) for 60 min/d, 0.737 (0.701, 0.776) for 30–60 min/d], independent of vitamin D intervention. Conclusions: High prevalence of vitamin D deficiency was found in children living at high latitudes. Vitamin D intervention and outdoor activity are all negatively associated with children’s vitamin D deficiency. Routine vitamin D intervention combined with increased outdoor time might be an effective approach to prevent hypovitaminosis D among children, especially those at school, living at high latitudes.
Transcriptomic analysis at organ and time scale reveals gene regulatory networks controlling the sulfate starvation response of Solanum lycopersicum.
Authors: Canales Javier , Uribe Felipe , Henríquez-Valencia Carlos , Lovazzano Carlos , Medina Joaquín , Vidal Elena A. 
Published: August 2020

Abstract
Background: Sulfur is a major component of biological molecules and thus an essential element for plants. Deficiency of sulfate, the main source of sulfur in soils, negatively influences plant growth and crop yield. The effect of sulfate deficiency on plants has been well characterized at the physiological, transcriptomic and metabolomic levels in Arabidopsis thaliana and a limited number of crop plants. However, we still lack a thorough understanding of the molecular mechanisms and regulatory networks underlying sulfate deficiency in most plants. In this work we analyzed the impact of sulfate starvation on the transcriptome of tomato plants to identify regulatory networks and key transcriptional regulators at a temporal and organ scale. Results: Sulfate starvation reduces the growth of roots and leaves which is accompanied by major changes in the organ transcriptome, with the response being temporally earlier in roots than leaves. Comparative analysis showed that a major part of the Arabidopsis and tomato transcriptomic response to sulfate starvation is conserved between these plants and allowed for the identification of processes specifically regulated in tomato at the transcript level, including the control of internal phosphate levels. Integrative gene network analysis uncovered key transcription factors controlling the temporal expression of genes involved in sulfate assimilation, as well as cell cycle, cell division and photosynthesis during sulfate starvation in tomato roots and leaves. Interestingly, one of these transcription factors presents a high identity with SULFUR LIMITATION1, a central component of the sulfate starvation response in Arabidopsis. Conclusions: Together, our results provide the first comprehensive catalog of sulfate-responsive genes in tomato, as well as novel regulatory targets for future functional analyses in tomato and other crops.
Retraction of transporting bone segment during Ilizarov bone transport
Authors: Ma Yunhong , Yin Qudong , Wu Yongwei , Wang Zongnan , Sun Zhenzhong , Gu Sanjun , Rui Yongjun , Han Xiaofei 
Published: August 2020

Abstract
Background: Retraction of transporting bone segment (TBS) may occur when the TBS fixator was removed prior to full consolidation of the distracted callus, which has adverse effect on the healing of the docking site. However, there are few reports on the retraction of TBS. The purpose of this study is to analyze the causes and risk factors of retraction of TBS.Methods: The clinical data of 37 cases with tibial bone defect treated by Ilizarov bone transport were analyzed retrospectively, in whom the TBS fixator was removed prior to full consolidation of the distracted callus and union of the docking site. Bivariate correlation was used to analyze relationship between the retraction distance of TBS and potential risk factors including age, gender, course, length of bone defect, number of operations, size of TBS, transport distance, timing and time interval of removal of TBS fixator. Risk factors with significant level were further identified using multivariate linear regression.Results: Bivariate correlation showed that the timing of removal was negatively correlated while the time interval and transport distance were positively correlated with the retraction distance（p<0.05), the age, gender, course, length of bone defect, size of TBS and number of operations were not correlated with the retraction distance（p>0.05). Multivariate linear regression of the 3 risk factors showed that the timing of removal and time interval were the main risk factors for the retraction distance (p<0.05), but the transport distance was not (p>0.05).Conclusion: The traction forces of TBS endured from the soft tissues and the unconsolidated distracted callus have elastic properties, which can make retraction of TBS. The timing of removal and time interval are the main factors of retraction distance. In the case of early removal, another external fixation should be performed or quickly converted to internal fixation to avoid the adverse effect of more retraction.
Effectiveness of the innovative 1,7-malaria reactive community-based testing and response (1, 7-mRCTR) approach on malaria burden reduction in Southeastern Tanzania
Authors: Mlacha Yeromin P. , Wang Duoquan , Chaki Prosper P. , Gavana Tegemeo , Zhou Zhengbin , Michael Mihayo G. , Khatib Rashid , Chila Godlove , Msuya Hajiran M. , Chaki Exavery , Makungu Christina , Lin Kangming , Tambo Ernest , Rumisha Susan F. , Mkude Sigbert , Mahende Muhidin K. , Chacky Frank , Vounatsou Penelope , Tanner Marcel , Masanja Honorati , Aregawi Maru , Hertzmark Ellen , Xiao Ning , Abdulla Salim , Zhou Xiao-Nong 
Published: August 2020

Abstract
BackgroundIn 2015, a China-UK-Tanzania tripartite pilot project was implemented in southeastern Tanzania to explore a new model for reducing malaria burden and possibly scaling-out the approach into other malaria-endemic countries. The 1,7-malaria Reactive Community-based Testing and Response (1,7-mRCTR) which is a locally-tailored approach for reporting febrile malaria cases in endemic villages was developed to stop transmission and Plasmodium life-cycle. The (1,7-mRCTR) utilizes existing health facility data and locally trained community health workers to conduct community-level testing and treatment.MethodsThe pilot project was implemented from September 2015 to June 2018 in Rufiji District, southern Tanzania. The study took place in four wards, two with low incidence and two with a higher incidence. One ward of each type was selected for each of the control and intervention arms. The control wards implemented the existing Ministry of Health programmes. The 1,7-mRCTR activities implemented in the intervention arm included community testing and treatment of malaria infection. Malaria case-to-suspect ratios at health facilities (HF) were aggregated by villages, weekly to identify the village with the highest ratio. Community-based mobile test stations (cMTS) were used for conducting mass testing and treatment. Baseline (pre) and endline (post) household surveys were done in the control and intervention wards to assess the change in malaria prevalence measured by the interaction term of ‘time’ (post vs pre) and arm in a logistic model. A secondary analysis also studied the malaria incidence reported at the HFs during the intervention.ResultsOverall the 85 rounds of 1,7-mRCTR conducted in the intervention wards significantly reduced the odds of malaria infection by 66% (adjusted OR 0.34, 95%CI 0.26,0.44, p<0001) beyond the effect of the standard programmes. Malaria prevalence in the intervention wards declined by 81% (from 26% (95%CI, 23.7,7.8), at baseline to 4.9% (95%CI, 4.0,5.9) at endline). In villages receiving the 1,7-mRCTR, the short-term case ratio decreased by over 15.7% (95%CI, -33,6) compared to baseline.ConclusionThe 1,7-mRCTR approach significantly reduced the malaria burden in the areas of high transmission in rural southern Tanzania. This locally tailored approach could accelerate malaria control and elimination efforts. The results provide the impetus for further evaluation of the effectiveness and scaling up of this approach in other high malaria burden countries in Africa, including Tanzania.