bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical outcomes of older patients with AML receiving hypomethylating agents: a large population-based study in the United States
Authors: Zeidan Amer M. , Wang Rong , Wang Xiaoyi , Shallis Rory M. , Podoltsev Nikolai A. , Bewersdorf Jan P. , Huntington Scott F. , Neparidze Natalia , Giri Smith , Gore Steven D. , Davidoff Amy J. , Ma Xiaomei
Published: May 2020

The hypomethylating agents (HMAs) azacitidine and decitabine have been the de facto standard of care for patients with acute myeloid leukemia (AML) who are unfit for intensive therapy. Using the Surveillance, Epidemiology, and End Results-Medicare linked database, we identified 2263 older adults (age ≥66 years) diagnosed with AML during 2005-2015 who received a first-line HMA; 1154 (51%) received azacitidine, and 1109 (49%) received decitabine. Median survival from diagnosis was 7.1 and 8.2 months (P < .01) for azacitidine- and decitabine-treated patients, respectively. Mortality risk was higher with azacitidine vs decitabine (hazard ratio [HR], 1.11; 95% confidence interval [CI], 1.01-1.21; P = .02). The findings were similar when evaluating only patients completing ≥4 cycles (42% of patients treated with either azacitidine or decitabine). These findings lost significance when evaluating those completing a standard 7-day schedule of azacitidine (34%) vs 5-day schedule for decitabine (66%) (HR, 0.95; 95% CI, 0.83-1.08; P = .43). Red blood cell (RBC) transfusion independence (TI) was achieved in one-third of patients with no difference between the 2 HMAs. In conclusion, the majority of older AML patients did not receive the minimum of 4 cycles of HMA often needed to elicit clinical benefit. We observed no clinically meaningful differences between azacitidine- and decitabine-treated patients in their achievement of RBC TI or survival.
Cloning of Hynobius lichenatus (Tohoku hynobiid salamander) p53 and analysis of its expression in response to radiation
Authors: Kamada Toshiki , Une Yumi , Matsui Kumi , Fuma Shoichi , Ikeda Teruo , Okamoto Mariko
Published: May 2020

Background

Caudata species such as salamanders are easily affected by environmental changes, which can drastically reduce their population. The effects of acute X-rays and chronic γ-irradiation on Hynobius lichenatus, the Japanese Tohoku hynobiid salamander, are known. However, the expression of radiation-inducible genes, such as the DNA-damage checkpoint response gene p53, has not been analyzed in H. lichenatus. This has not occurred because there is no established method for mRNA quantification in H. lichenatus due to a lack of information on available nucleotide sequences corresponding to both radiation-inducible genes and endogenous control genes such as ACTB (β-actin).

Results

In this study, we aimed to evaluate the effects of radiation on gene expression in H. lichenatus. Using RNA extracted from irradiated salamanders, we performed rapid amplification of cDNA ends (RACE) and cloned H. lichenatus β-actin, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and p53. We confirmed that the cloned cDNAs were able to synthesize salamander proteins by western blotting after transfection into cultured HEK293 cells. Proliferation assays using HEK293 cells stably expressing H. lichenatus p53 protein showed that this protein has antiproliferative effects, similar to that of mammalian p53. Furthermore, RT-qPCR analysis using gene-specific primers revealed that p53 mRNA expression in H. lichenatus was upregulated upon exposure to radiation.

Conclusion

Our results suggest that H. lichenatus p53 protein take an important role in regulating the cellular responses to various stimuli as mammalian p53 does. Furthermore, our study provides novel data to select appropriate primers to analyze internal control mRNA expression in H. lichenatus and to evaluate p53 expression as a marker of radiation and environmental stimuli.
Identification and validation of quantitative trait loci for ascites syndrome in broiler chickens using whole genome resequencing
Authors: Parveen Alia , Jackson Christa D. , Dey Shatovisha , Tarrant Katy , Anthony Nicholas , Rhoads Douglas D.
Published: May 2020

Background

Ascites syndrome is a hypertensive, multifactorial, multigene trait affecting meat-type chickens imposing significant economic losses on the broiler industry. A region containing the CPQ gene has been previously identified as significantly affecting ascites phenotype. The region was discovered through whole genome resequencing focused on chicken chromosome 2. The association was confirmed through further genotyping in multiple broiler populations.

Results

The whole genome resequencing analyses have now been extended to the current chicken genome assembly. DNA samples were pooled according to gender and phenotype and the pools subjected to next generation sequencing. Loci were identified as clusters of single nucleotide polymorphisms where frequencies of the polymorphisms differed between resistant and susceptible chickens. The chickens are an unselected line descended from a commercial elite broiler line. Regions identified were specific to one or both genders. The data identify a total of 28 regions as potential quantitative trait loci for ascites. The genes from these regions have been associated with hypertensive-related traits in human association studies. One region on chicken chromosome 28 contains the LRRTM4 gene. Additional genotyping for the LRRTM4 region demonstrates an epistatic interaction with the CPQ region for ascites phenotype.

Conclusions

The 28 regions identified were not previously identified in a multi-generational genome wide association study using 60k Single Nucleotide Polymorphism panels. This work demonstrates the utility of whole genome resequencing as a cost effective, direct, and efficient method for identifying specific gene regions affecting complex traits. The approach is applicable to any organism with a genome assembly and requires no a priori assumptions.
New perspectives on butyrate assimilation in Rhodospirillum rubrum S1H under photoheterotrophic conditions
Authors: De Meur Quentin , Deutschbauer Adam , Koch Matthias , Bayon-Vicente Guillaume , Cabecas Segura Paloma , Wattiez Ruddy , Leroy Baptiste
Published: May 2020

Background

The great metabolic versatility of the purple non-sulfur bacteria is of particular interest in green technology. Rhodospirillum rubrum S1H is an α-proteobacterium that is capable of photoheterotrophic assimilation of volatile fatty acids (VFAs). Butyrate is one of the most abundant VFAs produced during fermentative biodegradation of crude organic wastes in various applications. While there is a growing understanding of the photoassimilation of acetate, another abundantly produced VFA, the mechanisms involved in the photoheterotrophic metabolism of butyrate remain poorly studied.

Results

In this work, we used proteomic and functional genomic analyses to determine potential metabolic pathways involved in the photoassimilation of butyrate. We propose that a fraction of butyrate is converted to acetyl-CoA, a reaction shared with polyhydroxybutyrate metabolism, while the other fraction supplies the ethylmalonyl-CoA (EMC) pathway used as an anaplerotic pathway to replenish the TCA cycle. Surprisingly, we also highlighted a potential assimilation pathway, through isoleucine synthesis and degradation, allowing the conversion of acetyl-CoA to propionyl-CoA. We tentatively named this pathway the methylbutanoyl-CoA pathway (MBC). An increase in isoleucine abundance was observed during the early growth phase under butyrate condition. Nevertheless, while the EMC and MBC pathways appeared to be concomitantly used, a genome-wide mutant fitness assay highlighted the EMC pathway as the only pathway strictly required for the assimilation of butyrate.

Conclusion

Photoheterotrophic growth of Rs. rubrum with butyrate as sole carbon source requires a functional EMC pathway. In addition, a new assimilation pathway involving isoleucine synthesis and degradation, named the methylbutanoyl-CoA (MBC) pathway, could also be involved in the assimilation of this volatile fatty acid by Rs. rubrum.
Practice facilitation to promote evidence-based screening and management of unhealthy alcohol use in primary care: a practice-level randomized controlled trial
Authors: Huffstetler Alison N. , Kuzel Anton J. , Sabo Roy T. , Richards Alicia , Brooks E. Marshall , Lail Kashiri Paulette , Villalobos Gabriela , Arias Albert J. , Svikis Dace , Bortz Beth A. , Edwards Ashley , Epling John , Cohen Deborah J. , Parchman Michael L. , Winter Jonathan , Wessler Patricia , Yu Timothy J. , Krist Alex H.
Published: May 2020

Background

Unhealthy alcohol use is the third leading cause of preventable death in the United States. Evidence demonstrates that screening for unhealthy alcohol use and providing persons engaged in risky drinking with brief behavioral and counseling interventions improves health outcomes, collectively termed screening and brief interventions. Medication assisted therapy (MAT) is another effective method for treatment of moderate or severe alcohol use disorder. Yet, primary care clinicians are not regularly screening for or treating unhealthy alcohol use.

Methods and analysis

We are initiating a clinic-level randomized controlled trial aimed to evaluate how primary care clinicians can impact unhealthy alcohol use through screening, counseling, and MAT. One hundred and 25 primary care practices in the Virginia Ambulatory Care Outcomes Research Network (ACORN) will be engaged; each will receive practice facilitation to promote screening, counseling, and MAT either at the beginning of the trial or at a 6-month control period start date. For each practice, the intervention includes provision of a practice facilitator, learning collaboratives with three practice champions, and clinic-wide information sessions. Clinics will be enrolled for 6–12 months. After completion of the intervention, we will conduct a mixed methods analysis to identify changes in screening rates, increase in provision of brief counseling and interventions as well as MAT, and the reduction of alcohol intake for patients after practices receive practice facilitation.

Discussion

This study offers a systematic process for dissemination and implementation of the evidence-based practice of screening, counseling, and treatment for unhealthy alcohol use. Practices will be asked to implement a process for screening, counseling, and treatment based on their practice characteristics, patient population, and workflow. We propose practice facilitation as a robust and feasible intervention to assist in making changes within the practice. We believe that the process can be replicated and used in a broad range of clinical settings; we anticipate this will be supported by our evaluation of this approach.

Trial registration

ClinicalTrials.gov, ClinicalTrials.gov Identifier: NCT04248023, Registered 5 February 2020.
Insight into bladder cancer care: study protocol of a large nationwide prospective cohort study (BlaZIB)
Authors:   on behalf of the BlaZIB study group, Ripping T. M. , Kiemeney L. A. , van Hoogstraten L. M. C. , Witjes J. A. , Aben K. K. H.
Published: May 2020

Background

Despite the embedding of bladder cancer management in European guidelines, large variation in clinical practice exists for applied diagnostics and treatments. This variation may affect patients’ outcomes including complications, disease recurrence, progression, survival, and health-related quality of life (HRQL). Lack of detailed clinical data and HRQL data hampers a comprehensive evaluation of bladder cancer care. Through prospective data registration, this study aims to provide insight in bladder cancer care in the Netherlands and to identify barriers and modulators of optimal bladder cancer care.

Methods

This study is a nationwide prospective cohort study including all patients who were newly diagnosed with high-risk non-muscle invasive bladder cancer (HR-NMIBC; Tis and/or T1, N0, M0/x) or non-metastatic muscle invasive bladder cancer (MIBC; ≥T2, N0/x-3, M0/x) in the Netherlands between November 1st 2017 and October 31st 2019. Extensive data on patient- and tumor characteristics, diagnostics, treatment and follow-up up to 2 years after diagnosis will be collected prospectively from electronic health records in the participating hospitals by data managers of the Netherlands Cancer Registry (NCR). Additionally, patients will be requested to participate in a HRQL survey shortly after diagnosis and subsequently at 6, 12 and 24 months. The HRQL survey includes six standardized questionnaires, e.g. SCQ Comorbidity score, EQ-5D-5 L, EORTC-QLQ-C30, EORTC-QLQ-BLM30, EORTC-QLQ-NMIBC24 and BCI. Variation in care and deviation from the European guidelines will be assessed through descriptive analyses and multivariable multilevel analyses. Survival analyses will be used to assess the association between variation in care and relevant outcomes such as survival.

Discussion

The results of this observational study will guide modifications of clinical practice and/or adaptation of guidelines and may set the agenda for new specific research questions in the management of bladder cancer.

Trial registration

Retrospectively registered in the Netherlands Trial Register. Trial identification number: NL8106. Registered on October 22nd 2019.
Association of surgical margins with local recurrence in patients undergoing breast-conserving surgery after neoadjuvant chemotherapy
Authors: Lin Joseph , Lin Kuo-Juei , Wang Yu-Fen , Huang Ling-Hui , Chen Sam Li-Sheng , Chen Dar-Ren
Published: May 2020

Background

The aim of the current study was to report a single-institution experience using breast-conserving surgery after neoadjuvant chemotherapy (NACT), focusing on the association between microscopic resection margin status and locoregional recurrence (LRR).

Methods

Our institutional prospectively maintained database was reviewed to identify patients who were treated with NACT between January 2008 and April 2018.

Results

Among the main partial mastectomy specimens available for analysis (n = 161), 28 had margins < 1 mm, 21 had margin width of 1–2 mm and the remaining 112 had margins > 2 mm. LRR occurred in 16 patients (9.9%) and distant metastases were detected in 27 (16.8%) patients. There was no significant difference in the LRR between the > 2 mm margin group with a 60-month cumulative survival of 85.2% compared with 76.2% for the ≤2 mm group (P = 0.335) in the Kaplan-Meier analysis. When we stratified patients by margin widths of ≥1 mm or <  1 mm, there was no LRR-free survival benefit observed for the ≥1 mm pathologic excision margin group in the univariate analysis (hazard ratio = 0.443; 95% confidence interval = 0.142–1.383; P = 0.161) with a 60-month cumulative LRR-free survival of 84.9% compared with 69.5% for the < 1 mm margin cohort (P = 0.150).

Conclusions

In the absence of multiple scattered microscopic tumour foci, a negative margin of no ink on tumour maybe sufficient for stage I–III invasive breast cancer treated with NACT and breast-conserving surgery.
The introduction of risk stratified screening into the NHS breast screening Programme: views from British-Pakistani women
Authors: Woof Victoria G. , Ruane Helen , French David P. , Ulph Fiona , Qureshi Nadeem , Khan Nasaim , Evans D. Gareth , Donnelly Louise S.
Published: May 2020

Background

UK national guidelines suggest women at high-risk of breast cancer should be offered more frequent screening or preventative medications. Currently, only 1 in 6 high-risk women are identified. One route to identify more high-risk women is via multifactorial risk assessment as part of the UK’s NHS Breast Screening Programme (NHSBSP). As lower socioeconomic and minority ethnic populations continue to experience barriers to screening, it is important that any new service does not exacerbate issues further. To inform service development, this study explored views of women from underserved backgrounds regarding the introduction of risk stratification into the NHSBSP.

Methods

Nineteen semi-structured interviews were conducted with British-Pakistani women from low socioeconomic backgrounds from East Lancashire, UK. Fourteen interviews were conducted via an interpreter.

Results

Thematic analysis produced three themes. Attitudes toward risk awareness concerns the positive views women have toward the idea of receiving personalised breast cancer risk information. Anticipated barriers to accessibility emphasises the difficulties associated with women’s limited English skills for accessing information, and their I.T proficiency for completing an online risk assessment questionnaire. Acceptability of risk communication strategy highlights the diversity of opinion regarding the suitability of receiving risk results via letter, with the option for support from a healthcare professional deemed essential.

Conclusions

The idea of risk stratification was favourable amongst this underserved community. To avoid exacerbating inequities, this new service should provide information in multiple languages and modalities and offer women the opportunity to speak to a healthcare professional about risk. This service should also enable completion of personal risk information via paper questionnaires, as well as online.
Incidence of subsequent primary cancers and radiation-induced subsequent primary cancers after low dose-rate brachytherapy monotherapy for prostate cancer in long-term follow-up
Authors: Vuolukka Kristiina , Auvinen Päivi , Palmgren Jan-Erik , Aaltomaa Sirpa , Kataja Vesa
Published: May 2020

Background

As aging is the most significant risk factor for cancer development, long-term prostate cancer (PCa) survivors have an evident risk of developing subsequent primary cancers (SPCs). Radiotherapy itself is an additional risk factor for cancer development and the SPCs appearing beyond 5 years after radiotherapy in the original treatment field can be considered as radiation-induced subsequent primary cancers (RISPCs).

Methods

During the years 1999-2008, 241 patients with localized PCa who underwent low dose-rate brachytherapy (LDR-BT) with I125 and were followed-up in Kuopio University Hospital, were included in this study. In this study the incidences and types of SPCs and RISPCs with a very long follow-up time after LDR-BT were evaluated.

Results

During the median follow-up time of 11.4 years, a total of 34 (14.1%) patients developed a metachronous SPC. The most abundant SPCs were lung and colorectal cancers, each diagnosed in six patients (16.7% out of all SPCs). The crude incidence rate of RISPC was 1.7% (n = 4). Half of the SPC cases (50%) were diagnosed during the latter half of the follow-up time as the risk to develop an SPC continued throughout the whole follow-up time with the actuarial 10-year SPC rate of 7.0%. The crude death rates due to metachronous out-of-field SPCs and RISPCs were 50 and 50%, respectively.

Conclusion

The crude rate of SPC was in line with previously published data and the incidence of RISPC was very low. These results support the role of LDR-BT as a safe treatment option for patients with localized PCa.
Tumor-associated tissue eosinophilia predicts favorable clinical outcome in solid tumors: a meta-analysis
Authors: Hu Guoming , Wang Shimin , Zhong Kefang , Xu Feng , Huang Liming , Chen Wei , Cheng Pu
Published: May 2020

Background

Activated eosinophils have been deemed to affect carcinogenesis and tumor progression via various mechanisms in tumor microenvironment. However, the prognostic role of tumor-associated tissue eosinophilia (TATE) in human cancers remains controversial. Therefore, we conducted this meta-analysis to better comprehend the association between TATE and clinical outcomes of patients.

Methods

We searched PubMed, Embase and EBSCO to determine the researches assessing the association between TATE and overall survival (OS) and/or disease-free survival (DFS) in patients with cancer, then combined relevant data into hazard ratios (HRs) or odds ratio (OR) for OS, DFS and clinicopathological features including lymph node metastasis etc. with STATA 12.0.

Results

Twenty six researches with 6384 patients were included in this meta-analysis. We found that the presence of TATE was significantly associated with improved OS, but not with DFS in all types of cancers. In stratified analyses based on cancer types, pooled results manifested that the infiltration of eosinophils was remarkably associated with better OS in esophageal carcinoma and colorectal cancer. In addition, TATE significantly inversely correlated with lymph node metastasis, tumor stage and lymphatic invasion of cancer.

Conclusion

TATE promotes survival in cancer patients, suggesting that it is a valuable prognostic biomarker and clinical application of biological response modifiers or agonists promoting TATE may be the novel therapeutic strategy for patients.
Loneliness as a predictor of outcomes in mental disorders among people who have experienced a mental health crisis: a 4-month prospective study
Authors: Wang Jingyi , Lloyd-Evans Brynmor , Marston Louise , Mann Farhana , Ma Ruimin , Johnson Sonia
Published: May 2020

Background

Loneliness has not until recently been a prominent focus in research on outcomes of mental illness. The aim of this study was to determine whether loneliness at baseline predicts poor outcomes at 4-month follow-up for individuals who have experienced mental health crises. The outcomes in this study included overall symptom severity, affective symptoms, self-rated recovery and health-related quality of life.

Methods

Our study reports a secondary analysis of data from a randomised controlled trial. The sample (n = 399) was taken from patients who received treatment from community crisis services. Respondents (n = 310) completed the follow-up measurement 4 months after baseline. Loneliness at baseline was assessed using an eight-item UCLA Loneliness Scale. The four mental health outcomes were measured at both baseline and follow-up. Two scales (or part thereof) assessed objective social isolation and neighbourhood social capital at baseline. Regression analyses were conducted to investigate longitudinal associations between loneliness at baseline and mental health outcomes at follow-up.

Results

Loneliness at baseline was associated with all four mental health outcomes at 4-month follow-up, adjusting for psychosocial, socio-demographic and clinical characteristics. A one-point higher loneliness score was associated with 0.74-point (95% CI 0.45, 1.02) and 0.34-point (95% CI 0.21, 0.47) increase in overall symptom severity score and affective symptoms score respectively, and with 1.08-point (95% CI -1.45, − 0.71) and 1.27-point (95% CI -1.79, − 0.75) decrease in self-rated recovery score and health-related quality of life score respectively. Loneliness was a better predictor of clinical outcomes than objective social isolation and social capital, even though the associations with clinical outcomes were reduced and no longer statistically significant following adjustment for their baseline values. A significant association with quality of life persisted after adjustment for its baseline score.

Conclusions

Greater loneliness at baseline predicted poorer health-related quality of life at follow-up. There were cross-sectional associations between loneliness and clinical outcomes, but their longitudinal relationship cannot be confirmed. Further research is needed to clearly establish their underpinning pathways. Reducing loneliness may be a promising target to improve recovery for mental health community crisis service users.
Implementation of an interactive organ donation education program for Dutch lower-educated students: a process evaluation
Authors: Steenaart Esther , Crutzen Rik , de Vries Nanne K.
Published: May 2020

Background

As organ donation registration rates remain low, especially among lower-educated people, it is important to support this group in making their registration decision. To prepare lower-educated students in the Netherlands for making a well-informed decision, an interactive educational program was developed. We aim to understand both the (quality of) implementation as well as to contextualize the effects of this program in a lower-educated school setting.

Methods

The process evaluation was part of a Cluster Randomized Controlled Trial, in which 11 schools for Intermediate Vocational Education throughout the Netherlands participated. Teachers who taught a course on Citizenship delivered three intervention elements (i.e. video fragments and discussion, quizzes with tailored feedback and an exercise filling out a registration form) to their students. Implementation was assessed by interviews with teachers, questionnaires from students, logbooks from teachers and user data from Google Analytics.

Results

The program was well received and implemented, but on-the-spot adaptations were made by teachers to fit their students better. Within the lower-educated target group, differences between students are high in terms of active participation, reading abilities, knowledge and attention span. The program fit well within their regular teaching activities, but the topic of organ donation is not always prioritized by teachers.

Conclusions

We see opportunities to disseminate the program on a larger scale and reach a group that has been neglected in organ donation education before. Within the program, there are possibilities to increase the effectiveness of the program, such as alternative delivery methods for the elements with a lot of text, the addition of booster sessions and guidelines for teachers to adapt the program to students of different levels within Intermediate Vocational Education. Moreover, in order to have an impact on a national level, strategies need to be employed to reach high numbers of students and, therefore, support on a higher level is needed (both within schools and at policy level).

Trial registration

Dutch Trial Register, NTR6771. Prospectively registered on 24 October 2017.
Prospective multicentre validation study of a new standardised version of the 400-point hand assessment
Authors: Konzelmann Michel , Burrus Cyrille , Gable Colette , Luthi François , Paysant Jean
Published: May 2020

Background

Hand rehabilitation needs valid evaluation tools; the 400-point Hand Assessment (HA) is an exhaustive but not standardised tool. The aim of this study was to validate a standardised version of this test.

Methods

A modified version and a standardised prototype was made for this prospective validation study (four centres, three countries). Psychometric properties studied: reliability (intra-rater and inter-rater, standard error of measurement [SEM], minimum detectable change [MDC],internal consistency); content validity, construct validity with Jebsen Taylor hand function test, QuickDASH, MOS-SF 36 and pain; responsiveness, using an anchor-based approach (ROC curve with area under curve, mean response change) with calculation of MCID. For SEM, MDC and responsiveness, QuickDASH was used for comparison.

Results

One hundred and seventy-six patients with hand/wrist injuries were included between May 2013 and February 2015. One hundred and seventy were available for final analysis: 67% men; mean age 43.4 ± 13.2 years; both manual and office workers (46, 5% of each); 37% had a hand or wrist fracture.

Reliability: ICC intra-rater = 0.967 [0.938–0.982]; inter-rater = 0.868 [0.754–0.932]. Distribution-based approach: for 400-point HA/QuickDASH: SEM = 3.48/4.52, MDC = 9.065/12.53, internal consistency of 400-point HA: Cronbach α = 0.886.

Validity: Content validity was good according to COSMIN guidelines. Construct validity: correlation coefficient: Jebsen-Taylor hand function test = − 0.573 [− 0.666–0.464], QuickDASH = − 0.432 at T0 [− 0.545–0.303], − 0.551 at T3 [− 0.648–0.436]; MOS-SF 36 physical component = 0.395 [0.263–0.513]; no correlation with MOS-SF 36 mental component = 0.142 [− 0.009 + 0.286] and pain = − 0.166 [− 0.306 + 0.018].

Responsiveness: Anchor-based approach: AUC Δ400-point HA = 0.666 [0.583–0.749], AUC ΔQuickDASH = 0.556 [0.466–0.646]. MCID (optimal ROC curve cut-off): 6.07 for 400-point HA, − 2.27 for QuickDASH. MCID with mean response change + 12.034 ± 9.067 for 400-point HA and − 8.03 ± –9.7 for QuickDASH. The patient’s global impression of change was only correlated with the Δ400-point HA.

Conclusions

The 400-point HA standardised version has good psychometric properties. For responsiveness, we propose an MCID of at least 12.3/100. However, these results must be confirmed in other populations and pathologies.

Trial registration

This study was retrospectively registered into ISCTRN registry (Number ISRCTN25874481) the 07/02/2019.
Antiseptics as adjuncts to scaling and root planing in the treatment of periodontitis: a systematic literature review
Authors: Ramanauskaite Egle , Machiulskiene Vita
Published: May 2020

Background

Periodontitis is microbially-associated, host-mediated inflammatory condition that results in loss of periodontal attachment. The goals of periodontal therapy include arresting the disease progression, establishing healthy, stable, maintainable periodontal conditions. A fundamental strategy of treating periodontitis is scaling and root planning (SRP), however its efficacy may be restricted in areas inaccessible for mechanical instrumentation. As periodontitis is infectious in nature, it might be helpful to use additional antimicrobial adjuncts, in order to eliminate or inactivate pathogenic microflora. The aim of this study is to evaluate the current evidence regarding the potential clinical benefits of using additional antiseptics for SRP in nonsurgical periodontal therapy.

Methods

An electronic literature search was conducted in the MEDLINE (Ovid) and Cohrane Central Register of Controlled Trials (CENTRAL) databases for articles published between January 1, 2000 and September 22, 2019. Randomized controlled clinical trials in English that compare the effectiveness of one or more antiseptic agents as adjuncts to SRP with a follow-up of ≥6 months were included. A meta-analysis using the random-effects model was performed on the selected qualifying articles.

Results

The search resulted in 12 articles that met the inclusion criteria. Based on the vehicle employed to deliver the antiseptic agent, studies were divided into adjunctive sustained-release antiseptics (gels, chips and varnish) and adjunctive irrigation with antiseptics. The meta-analysis demonstrated significant improvements in probing depth (PD) reduction (p = 0.001), clinical attachment level (CAL) gain (p = 0.001), and bleeding on probing (BOP) values (p = 0.001) following the adjunctive subgingival application of sustained-release antiseptics. Additional subgingival irrigation with antiseptics failed to show significant improvements in PD (p = 0.321), CAL (p = 0.7568), or BOP values (p = 0.3549) over SRP alone.

Conclusions

Adjunctive subgingivally delivered antiseptics with a sustained-release delivery have significant clinical benefits compared to SRP alone.
The economic burden of prostate cancer – a Swedish prevalence-based register study
Authors: Hao Shuang , Östensson Ellinor , Eklund Martin , Grönberg Henrik , Nordström Tobias , Heintz Emelie , Clements Mark
Published: May 2020

Background

Incidence and prevalence of prostate cancer in Sweden have increased markedly due to prostate-specific antigen (PSA) testing. Moreover, new diagnostic tests and treatment technologies are expected to further increase the overall costs. Our aims were (i) to estimate the societal costs for existing testing, diagnosis, management and treatment of prostate cancer, and (ii) to provide reference values for future cost-effectiveness analyses of prostate cancer screening and treatment.

Methods

Taking a societal perspective, this study aimed to investigate the annual cost of prostate cancer in Sweden using a prevalence-based cost-of-illness approach. Resource utilisation and related costs within Stockholm Region during 2016 were quantified using data from the Stockholm PSA and Biopsy Register and other health and population registers. Costs included: (i) direct medical costs for health care utilisation at primary care, hospitals, palliative care and prescribed drugs; (ii) informal care; and (iii) indirect costs due to morbidity and premature mortality. The resource utilisation was valued using unit costs for direct medical costs and the human capital method for informal care and indirect costs. Costs for the Stockholm region were extrapolated to Sweden based on cancer prevalence and the average costs by age and resource type.

Results

The societal costs due to prostate cancer in Stockholm in 2016 were estimated to be €64 million Euro (€Mn), of which the direct medical costs, informal care and productivity losses represented 62, 28 and 10% of the total costs, respectively. The total annual costs extrapolated to Sweden were calculated to be €281 Mn. The average direct medical cost, average costs for informal care and productivity losses per prevalent case were €1510, €828 and €271, respectively. These estimates were sensitive to assumptions related to the proportion of primary care visits associated with PSA testing and the valuation method for informal care.

Conclusion

The societal costs due to prostate cancer were substantial and constitute a considerable burden to Swedish society. Data from this study are relevant for future cost-effectiveness evaluations of prostate cancer screening and treatment.
Overactive bladder in an integrated delivery system: a longitudinal cohort study
Authors: Linder Jeffrey A. , Weissman Joel S. , Reyes Nieva Harry , Lipsitz Stuart , Haring R. Sterling , DeAngelis Julie , Kristy Rita M. , Loughlin Kevin R.
Published: May 2020

Background

Overactive bladder (OAB) is common and morbid. Medication and diagnosis claims may be specific, but lack sensitivity to identify patients with overactive bladder. We used an “electronic health record (EHR) phenotype” to identify cases and describe treatment choices and anticholinergic burden for OAB.

Methods

We conducted a retrospective cohort study in a large, integrated health delivery system between July 2011 and June 2012 (2-year follow-up). We examined care from primary care and specialty clinics, medication and procedure use, and anticholinergic burden for each patient.

Results

There were 7362 patients with an EHR OAB phenotype; 50% of patients were > 65 years old, 74% were female, and 83% were white. The distribution of care included primary care physician (PCP)/specialty co-management (25% of patients); PCP care only (18%); urology only (13%); or some other combination of specialty care (33%). Only 40% of patients were prescribed at least 1 OAB medication during the study. The mean duration of prescribed medication was 1.5 months (95% confidence interval [CI], 1.4 to 1.6 months; range, < 1 month to 24 months). Independent predictors of receipt of an OAB medication included increasing age (odds ratio [OR], 1.4 for every 10 years; 95% CI, 1.4 to 1.5), women (OR, 1.6 compared with men; 95% CI, 1.4 to 1.8), diabetes (OR, 1.3; 95% CI, 1.1 to 1.5), and certain sources of care compared with PCP-only care: PCP/specialty co-management (OR, 1.8; 95% CI, 1.5 to 2.0), urology (OR, 2.2; 95% CI, 1.8 to 2.6), and multiple specialists (OR, 1.4; 95% CI, 1.2 to 1.8). Very few patients received other treatments: biofeedback (< 1%), onabotulinumtoxinA (2%), or sacral nerve stimulation (1%). Patients who received OAB medications had significantly higher anticholinergic burden than patients who did not (anticholinergic total standardized daily dose, 125 versus 46;P < .001).

Conclusions

Although OAB is common and morbid, in a longitudinal study using an EHR OAB phenotype 40% of patients were treated with OAB medication and only briefly.
Effect of dietary supplementation of alpha-galactosidase on the growth performance, ileal digestibility, intestinal morphology, and biochemical parameters in broiler chickens
Authors: Amer Shimaa A. , Naser Mohamed A. F. , Abdel-Wareth Ahmed A. A. , Saleh Ahmed A. , Elsayed Shafika A. M. , Abdel fattah Doaa M. , Metwally Abdallah E.
Published: May 2020

Background

This study was performed to investigate the effect of Alpha-galactosidase (AlphaGal) supplementation with two energy levels on the growth performance, amino acid ileal digestibility coefficient “AID%,” economic value, intestinal histology, and blood biochemical parameters of broiler chickens. Two-hundred 3-day-old broiler chicks (average body weight 74.34 g ±0.52 Ross 308) were randomly assigned to a 2 × 2 factorial arrangement consisting of two energy diets groups: in the first group, the birds were fed on a recommended energy diet (RED) while the second group was reduced 120 kcal/kg diet as a low energy diet (LED) and two levels of AlphaGal (0 or 50 mg/kg diet) for RED and LED for the 35-day feeding period.

Results

The interaction effects between the energy level and the AlphaGal supplementations resulted in significant decrease (P ≤ 0.05) in the body weight, body weight gain, and the relative growth rate. The feed conversion ratio was signficantly increased in LED without supplementation of AlphaGal group during the entire experimental period, this negative effect on the growth performance was corrected by AlphaGal supplementation. The AID% value was increased significantly by AlphaGal supplementation. Blood triglyceride concentrations were significantly decreased (P = 0.02) in the LED group with or without AlphaGal supplementation, while the level of high-density lipoprotein (HDL) was significantly decreased (P = 0.01) in the LED or RED groups supplemented with 50 mg RED AlphaGal. Histologically, the number of intestinal glands and goblet cells increased in both RED and LED groups supplemented with AlphaGal and their secretions were mainly neutral mucopolysaccharides and less acidic mucopolysaccharides.

Conclusion

AlphaGal supplementation improved the growth performance of broiler chickens fed LED and the growth performance is similar to those fed RED, thereby consequently improving the economic value of these diets. AlphaGal supplementation improves intestinal histology and morphology as well.
Extremely high canine C-reactive protein concentrations > 100 mg/l – prevalence, etiology and prognostic significance
Authors: Hindenberg Sarah , Bauer Natali , Moritz Andreas
Published: May 2020

Background

In human medicine, extremely high CRP (C-reactive protein) concentrations > 100 mg/l are indicators of bacterial infection and the need of antibiotic treatment. Similar decision limits for septic pneumonia are recommended for dogs but have not yet been evaluated for other organ systems. The aim of the retrospective study was to investigate the prevalence and evaluate dogs with CRP concentrations > 100 mg/l regarding the underlying etiology, the affected organ system and the prognostic significance.

Results

Prevalence of CRP > 100 mg/l was investigated in dogs presented between 2014 and 2015 and was 12%.

For evaluation of etiology and organ systems, dogs with CRP > 100 mg/l presented between 2014 and 2016 were enrolled. Dogs were classified into 4 main disease categories, i.e. inflammatory, neoplastic, tissue damage or “diverse”. Diseases were assigned to the affected organ system. If an organ classification was not possible, dogs were classified as “multiple”. 147 dogs with CRP 101–368 mg/l were included and classified into disease categories: 86/147 (59%) with inflammatory etiology (among these, 23/86 non-infectious, 44/86 infectious (33/44 bacterial), 19/86 inflammation non-classifiable), 31/147 (21%) tissue damage, 17/147 (12%) neoplastic (all malignant) and 13/147 (9%) diverse diseases. The affected organ systems included 57/147 (39%) multiple, 30/147 (20%) trauma, 21/147 (14%) gastrointestinal tract, 10/147 (7%) musculoskeletal system, 8/147 (5%) respiratory tract, 7/147 (5%) urinary/reproductive tract, 6/147 (4%) skin/subcutis/ear, 6/147 (4%) central/peripheral nervous system and 2/147 (1%) heart. The disease group (p = 0.081) or organ system (p = 0.17) did not have an impact on CRP. Based on CRP, a detection of bacterial infection was not possible.

The prognostic significance was investigated by determining the 3-months survival and hospitalization rate in a subgroup with known outcome. The 3-months survival rate was 46/73 (63%) while the majority 66/73 (90%) of patients was hospitalized.

Conclusions

CRP concentrations > 100 mg/l are occasionally seen in a clinic population. They indicate a severe systemic disease of various etiologies with guarded prognosis. Extremely high CRP concentrations do not allow a conclusion of the underlying etiology or an identification of bacterial inflammation.
Antifibrotic therapy to normalize the tumor microenvironment
Authors: Hauge Anette , Rofstad Einar K.
Published: May 2020

Most tumors develop abnormal fibrotic regions consisting of fibroblasts, immune cells, and a dense extracellular matrix (ECM) immersed in a viscous interstitial fluid, and an abundant fibrotic tumor microenvironment (TME) is associated with poor outcome of treatment. It has been hypothesized that the treatment of cancer may be improved by interventions aiming to normalize this TME. The approaches used in attempts to normalize the fibrotic TME can be categorized into three strategies of targeted antifibrotic therapy: targeting of components of the ECM, targeting of the producers of the ECM components—the activated cancer-associated fibroblasts (CAFs), and targeting of the signaling pathways activating CAFs. To target the ECM, enzymes against components of the ECM have been used, including collagenase, relaxin, hyaluronidase, and lyxyl oxidase. Targeting of CAFs have been investigated by using agents aiming to eliminate or reprogram CAFs. CAFs are activated primarily by transforming growth factor-β (TGF-β), hedgehog, or focal adhesion kinase signaling, and several agents have been used to target these signaling pathways, including angiotensin II receptor I blockers (e.g., losartan) to inhibit the TGF-β pathway. Taken together, these studies have revealed that antifibrotic therapy is a two-edged sword: while some studies suggest enhanced response to treatment after antifibrotic therapy, others suggest that antifibrotic therapy may lead to increased tumor growth, metastasis, and impaired outcome of treatment. There are several possible explanations of these conflicting observations. Most importantly, tumors contain different subpopulations of CAFs, and while some subpopulations may promote tumor growth and metastasis, others may inhibit malignant progression. Furthermore, the outcome of antifibrotic therapy may depend on stage of disease, duration of treatment, treatment-induced activation of alternative profibrotic signaling pathways, and treatment-induced recruitment of tumor-supporting immune cells. Nevertheless, losartan-induced suppression of TGF-β signaling appears to be a particularly promising strategy. Losartan is a widely prescribed antihypertensive drug and highly advantageous therapeutic effects have been observed after losartan treatment of pancreatic cancer. However, improved understanding of the mechanisms governing the development of fibrosis in tumors is needed before safe antifibrotic treatments can be established.
Anterior approach with mini-bikini incision in open reduction in infants with developmental dysplasia of the hip
Authors: Jia Guoqiang , Wang Enbo , Lian Peng , Liu Tianjing , Zhao Shuyi , Zhao Qun
Published: May 2020

Purpose

The anterior and medial approaches in open reduction for developmental dysplasia of the hip (DDH) had been widely used. The former could not directly approach the intra-articular interposition, while the latter had been associated with injury to blood vessel and avascular necrosis (AVN) of the femoral head. Meanwhile, the bikini incision had also been mentioned in some studies. The purpose of this study was to introduce a modified anterior approach through a mini-bikini incision and report its short-term outcomes.

Methods

Data of DDH patients younger than 2 years at the time of surgery who had received this mini-bikini incision between June 2013 and December 2018 were collected. The surgical technique, operation duration, intraoperative blood loss, and length of incision were recorded in detail. In the latest follow up, the objective measurement of the scar and the subjective feeling towards the scar were collected. X-ray and magnetic resonance imaging (MRI) were performed at the last follow-up, and the incidence of residual dysplasia, redislocation, and femoral head AVN was analyzed.

Results

Forty-three cases (49 hips) were included with an averaged follow-up of 43 months. The operation duration was 22 min, and the blood loss was 9.8 ml on average. The length of the scar averaged 2.6 cm. The mean University of North Carolina “4P” scar scale (UNC4P) for the scar was 0.92, and no patients complained numbness. Overall, all the parents were satisfied with the cosmetic appearance. The mean acetabular index (AI) was 27.42° ± 6.41° in dislocated hip in the last follow-up. One hip redislocated soon after the operation and was reduced in a closed manner right away. MRI showed improved coverage but still some residual dysplasia that was in accordance with the post-operative recovery nature. Four hips (8%) had signs of AVN in X-ray.

Conclusion

Open reduction through the anterior approach with the mini-bikini incision was a safe procedure with comparable outcomes to classical approaches. It would be a complementary approach for DDH patients younger than 2 years old who need an open reduction.
Correction to: A window-of-opportunity trial of the CXCR1/2 inhibitor reparixin in operable HER-2-negative breast cancer
Authors: Goldstein Lori J. , Perez Raymond P. , Yardley Denise , Han Linda K. , Reuben James M. , Gao Hui , McCanna Susan , Butler Beth , Ruffini Pier Adelchi , Liu Yi , Rosato Roberto R. , Chang Jenny C.
Published: May 2020

An amendment to this paper has been published and can be accessed via the original article.
Gapless assembly of maize chromosomes using long-read technologies
Authors: Liu Jianing , Seetharam Arun S. , Chougule Kapeel , Ou Shujun , Swentowsky Kyle W. , Gent Jonathan I. , Llaca Victor , Woodhouse Margaret R. , Manchanda Nancy , Presting Gernot G. , Kudrna David A. , Alabady Magdy , Hirsch Candice N. , Fengler Kevin A. , Ware Doreen , Michael Todd P. , Hufford Matthew B. , Dawe R. Kelly
Published: May 2020

Creating gapless telomere-to-telomere assemblies of complex genomes is one of the ultimate challenges in genomics. We use two independent assemblies and an optical map-based merging pipeline to produce a maize genome (B73-Ab10) composed of 63 contigs and a contig N50 of 162 Mb. This genome includes gapless assemblies of chromosome 3 (236 Mb) and chromosome 9 (162 Mb), and 53 Mb of the Ab10 meiotic drive haplotype. The data also reveal the internal structure of seven centromeres and five heterochromatic knobs, showing that the major tandem repeat arrays (CentC, knob180, and TR-1) are discontinuous and frequently interspersed with retroelements.