bluuebunny/crossref_metadata_2025 huggingface dataset:
Potential of rutabaga (Brassica napus var. napobrassica) gene pool for use in the breeding of hybrid spring Brassica napus canola
Authors: Shiranifar Bijan , Hobson Neil , Kebede Berisso , Yang Rong‐Cai , Rahman Habibur
Published: February 2021

The use of rutabaga for increasing the level of heterosis in spring canola was investigated. For this, test hybrids were produced by crossing four inbred populations, derived from F2 and BC1 of two rutabaga × spring canola crosses, to their spring canola parent, and were tested in field‐plots for agronomic and seed quality traits. Average mid‐parent heterosis (MPH) in these test hybrid populations was about 5%‐15% for yield. Compared to the F2‐derived population, the BC1‐derived population exhibited 1.8‐times greater MPH for yield. No correlation was found between inbred and test hybrid for yield; however, a positive correlation of genetic diversity of the inbred lines was found with MPH (r = .58) and hybrid yield (r = .36) suggesting that non‐additive effect of the genes may play an important role for high yield in hybrids. About 2% negative MPH was found for days to flowering, while almost no heterosis was found for seed oil and protein contents. Thus, our study demonstrates the potential of the rutabaga gene pool for use in hybrid canola breeding.
Inherited genetic late‐onset erythropoietic protoporphyria: A systematic review of the literature
Authors: Noyman Yehonatan , Edel Yonatan , Snast Igor , Sherman Shany , Kaftory Ran , Lapidoth Moshe , Mimouni Daniel , Hodak Emmilia , Levi Assi
Published: February 2021

Background

Inherited genetic erythropoietic protoporphyria (EPP) is characterized by a photosensitive rash that emerges during infancy or early childhood. Acquired EPP can erupt at any age, even during adulthood, and is associated with hematological disorders. A third, less‐studied type of EPP is also inherited but appears later in life (during adulthood).

Purpose

To evaluate the characteristics of inherited genetic late‐onset (IGLO) EPP.

Methods

A systematic comprehensive search of the literature was conducted using PubMed, Google Scholar, ScienceDirect, and clinicaltrials.gov databases. Studies describing patients with IGLO EPP were included. Additionally, we present an index case of a patient, treated at our clinic in whom inherited genetic EPP was diagnosed at age 21 years.

Results

The search yielded 1514 citations. Five publications were eligible for review. Along with our case, 7 patients (4 males) were included in the analysis. Mean age at disease onset was 34.2 years (range 18‐69, median 30). Most patients presented with mild pruritus and rash in a photosensitive distribution. Mean level of free erythrocyte protoporphyrin IX (FEP) was 8.6 μmol/L. A mutant ferrochelatase gene (FECH) in trans to a hypomorphic FECH allele was found in 3 of the 4 patients who underwent genetic testing.

Conclusion

We describe the distinct features of IGLO EPP. This work emphasizes that a diagnosis of inherited genetic EPP should not be ruled out in adults with new‐onset photosensitive manifestations.
Treatment of dental caries in a patient with Joubert syndrome without the use of sedatives: A case study
Authors: Oda Yuki , Yoshida Keita , Furutani Chiaki , Wakita Atsuko , Hama Yoko , Miyauchi Miwa , Okada Yoshiyuki
Published: February 2021

Background

Joubert syndrome (JS) is a rare autosomal recessive inherited ciliopathy caused by gene mutation. Manifestations can include intermittent dyspnea, apnea, ataxia, and other nervous system abnormalities.

Case presentation

The patient was a 21‐year‐old female with JS, severe intellectual disability, cerebral palsy, and epilepsy. Dental caries in both mandibular lower first molars was diagnosed by a local dentist, and the patient was referred to us for further treatment. Although her oral hygiene was good, the dental caries had reached the vicinity of the dental pulp. The caries had developed symmetrically on both first molars and was completely covered with the gingiva. As she was hesitant to receive treatment without anxiolysis, we considered using general anesthesia or intravenous sedation. However, we were recommended against it by the patient's family doctor because of the risk of apneic episodes in JS. Accordingly, dental treatment was performed over multiple days through physical behavior adjustment, while providing oxygenation (3 L/min) in preparation for an apneic episode. The dental treatment was successfully completed with a good postoperative outcome.

Conclusions

Dental treatment can be safely performed in patients with JS through physical behavior adjustment, thereby minimizing the risk of an apnea attack.
Organizational Commitment and Labor Satisfaction. Case: A University Organization in the State of Morelos. México
Authors: Arévalo Ana Laura Uscanga , Mayo Augusto Renato Pérez , Nieto Nohemí Roque
Published: February 2021

This article measures two organizational factors of importance for every organization: labor satisfaction and organizational commitment. The analysis is made under the perspective of the sociology of organizations: Frederick Herzberg's theory of the two factors of motivation (hygienic and motivational) and Meyer and Allen's model of the three components of organizational commitment (1990). The methodology is empirical, descriptive and quantitative. The study was carried out with a sample of 59 employees, classified as reliable personnel of the Academic Secretary of an Institution of Higher Education (IES) in the city of Cuernavaca, Morelos. The instruments used were two questionnaires emanated from the theory itself with the purpose of knowing aspects related to the two study variables. This instrument allowed to identify the types of organizational commitment and the levels of work satisfaction and satisfaction that exist in the university organization.
Development of a Virtual Training Program to Reduce Gun Violence Amidst the Covid-19 Era
Authors: Chen Ping-Hsin , Kong Yu Tina , Emanuel Jasmine , Pan Megan
Published: February 2021

Firearm deaths and related health issues have increased and disproportionately affected minorities in the COVID-19 era. We developed an accessible virtual training program, including topics on gun violence epidemiology, depression, substance use, intimate partner violence (IPV), intervention resources, safety planning, and COVID-19-related issues. The training program was distributed to participants from the Northeast region, particularly New Jersey, through text, email, and social media. Among the 202 survey responses from the participants, the mean age was 22.6, 50% were male, and 84.4% were minorities. Only 49.5% of participants were familiar with the related topics before the program, with participants having the least knowledge in gun violence epidemiology (9.5%). The mean test score for knowledge on all related topics after the training was 98.0 out of 100. Most participants were satisfied with the training program (92.1%), felt comfortable seeking help (86.1%), and would promote the program (83.7%). The participants were least comfortable seeking help for depression, particularly among non-African and non-Hispanic minority groups. We concluded that brief online interventions can improve community health outreach, knowledge, awareness, and likelihood of help-seeking and treatment. Tailored training programs are needed to target various populations for prevention and intervention.
DBA/1 mice display equivalent cardiac function to C57BL/6J mice
Authors: Wang Zhen , Zhou Zhengwei , Guo Paipai , Wang Manman , Sun Hanfei , Tai Yu , Xiao Feng , Han Yongsheng , Wei Wei , Wang Qingtong
Published: February 2021

New Findings

What is the central question of this study?

Do normal adult DBA/1 mice have cardiac function and performance equal to those of C57BL/6J mice?

What is the main finding and its importance?

Male adult DBA/1 mice show equivalent cardiac function to C57BL/6J mice up to 8 months old. Therefore, cardiac dysfunction could be investigated in an autoimmune diseases model established with DBA/1 mice.

Cardiovascular mortality has been increasing, and in particular, cardiovascular damage caused by some chronic autoimmune diseases accounts for a large proportion of this. C57BL/6J mice have been used mostly in studies of cardiovascular diseases. However, for purposes of modelling, this strain of mouse has a very low incidence of some chronic immune diseases such as rheumatoid arthritis, to which instead DBA/1 mice are more susceptible. Basic cardiac function differs between mice with different genetic backgrounds. Therefore, we monitored cardiac function and structure of normal male C57BL/6J and DBA/1 mice for six consecutive months. Echocardiography was used to monitor cardiac functions once a month and cardiac systolic function was measured upon isoproterenol challenge at the end of observation. The Excitation–contraction coupling‐related proteins were measured by western blotting. Heart tissue sections were subject to haematoxylin–eosin, TUNEL and Alizarin red staining. The results demonstrated that systolic and diastolic function did not vary significantly and both strains were indistinguishable in appearance and structure of hearts. DBA/1 mice showed a good cardiac β‐adrenergic response comparable to C57BL/6J mice with isoproterenol treatment. The phosphorylation of phospholamban at either its protein kinase A or its Ca2+/calmodulin‐dependent protein kinase II site, as well as the activation of troponin I showed no significant difference between strains. These findings suggested that there was no obvious difference in the heart structure and function of normal male DBA/1 mice compared with C57BL/6J mice. The DBA/1 mouse is a strain applicable to investigating autoimmune disease‐induced heart dysfunction and exploring potential interventions.
Deciphering the “Art” in Modeling and Simulation of the Knee Joint: Variations in Model Development
Authors: Rooks Nynke B. , Schneider Marco T. Y. , Erdemir Ahmet , Halloran Jason P. , Laz Peter J. , Shelburne Kevin B. , Hume Donald R. , Imhauser Carl W. , Zaylor William , Elmasry Shady , Schwartz Ariel , Chokhandre Snehal K. , Abdollahi Nohouji Neda , Besier Thor F.
Published: February 2021

The use of computational modeling to investigate knee joint biomechanics has increased exponentially over the last few decades. Developing computational models is a creative process where decisions have to be made, subject to the modelers' knowledge and previous experiences, resulting in the “art” of modeling. The long-term goal of the KneeHub project is to understand the influence of subjective decisions on the final outcomes and the reproducibility of computational knee joint models. In this paper, we report on the model development phase of this project, investigating model development decisions and deviations from initial modeling plans. Five teams developed computational knee joint models from the same dataset, and we compared each teams' initial uncalibrated models and their model development workflows. Variations in the software tools and modeling approaches were found, resulting in differences such as the representation of the anatomical knee joint structures in the model. The teams consistently defined the boundary conditions and used the same anatomical coordinate system convention. However, deviations in the anatomical landmarks used to define the coordinate systems were present, resulting in a large spread in the kinematic outputs of the uncalibrated models. The reported differences and similarities in model development and simulation presented here illustrate the importance of the “art” of modeling and how subjective decision-making can lead to variation in model outputs. All teams deviated from their initial modeling plans, indicating that model development is a flexible process and difficult to plan in advance, even for experienced teams.
Design of a Quadratic, Antagonistic, Cable-Driven, Variable Stiffness Actuator
Authors: Moore Ryan , Schimmels Joseph M.
Published: February 2021

Antagonistically actuated variable stiffness actuators (VSAs) take inspiration from biological muscle structures to control both the stiffness and positioning of a joint. This paper presents the design of an elastic mechanism that utilizes a cable running through a set of three pulleys to displace a linear spring, yielding quadratic spring behavior in each actuator. A joint antagonistically actuated by two such mechanisms yields a linear relationship between force and deflection from a selectable equilibrium position. A quasi-static model is used to optimize the mechanism. Testing of the fabricated prototype yielded a good match to the desired elastic behavior.
Unknown Parameter Excitation and Estimation for Complex Systems With Dynamic Performances
Authors: Chen Yi-Ping , Chan Kuei-Yuan
Published: February 2021

Simulation models play crucial roles in efficient product development cycles, therefore many studies aim to improve the confidence of a model during the validation stage. In this research, we proposed a dynamic model validation to provide accurate parameter settings for minimal output errors between simulation models and real model experiments. The optimal operations for setting parameters are developed to maximize the effects by specific model parameters while minimizing interactions. To manage the excessive costs associated with simulations of complex systems, we propose a procedure with three main features: the optimal excitation based on global sensitivity analysis (GSA) is done via metamodel techniques, for estimating parameters with the polynomial chaos-based Kalman filter, and validating the updated model based on hypothesis testing. An illustrative mathematical model was used to demonstrate the detail processes in our proposed method. We also apply our method on a vehicle dynamic case with a composite maneuver for exciting unknown model parameters such as inertial and coefficients of the tire model; the unknown model parameters were successfully estimated within a 95% credible interval. The contributions of this research are also underscored through multiple cases.
An Experimental Study on Dynamic Properties of Rubber Specimens for a Crankshaft Torsional Vibration Damper of Automobiles
Authors: Honda Yasuhiro , Wakabayashi Katsuhiko , Kodama Tomoaki , Okamura Hiroshi
Published: February 2021

Torsional vibration occurs at a crankshaft system of operating multi-cylinder reciprocating engine in mechanism. A torsional vibration rubber damper is generally used to control or reduce the torsional vibration appearing at the crankshaft system of small diesel engine for automobile. Since automotive diesel engines have recently become engine weight lightening and higher performance output, both the amplitudes and the frequencies of the torsional vibrations generate increasingly more than before. Therefore, the torsional rubber damper should be required as one of the most important engine vibration reduction devices. The torsional vibration rubber damper must be precisely designed to match with a crankshaft system of engine with which it is mounted in order to reduce sufficiently. However, the prediction difficulty of its dynamic characteristics gives damper designers the design of a torsional rubber damper with variable experiments. While this design method requires too much time for examination of the vibration reduction effects obtained from some torsional oscillation tests, it is doubt whether the designed torsional damper will be able to sufficiently reduce the torsional vibration in variable engine operations. This paper refers to influences of rubber shape and forced frequency on properties of test rubber specimens designed for contribution to damper design.

Furthermore, some important subjects on properties of rubber are described for design of shear-type torsional rubber dampers by using a rheological model. The rubber properties can be obtained from exciting vibration tests of rubber specimens with the changes of exciting frequency, amplitude and temperature. It is confirmed that the shape factor should be reduced to suppress the influence on rubber dynamic properties of external factors such as amplitude and frequency.
Shear wave dispersion analysis of incompressible waveguides
Authors: Roy Tuhin , Guddati Murthy N.
Published: February 2021

A suite of methodologies is presented to compute shear wave dispersion in incompressible waveguides encountered in biomedical imaging; plate, tube, and general prismatic waveguides, all immersed in an incompressible fluid, are considered in this effort. The developed approaches are based on semi-analytical finite element methods in the frequency domain with a specific focus on the complexities associated with the incompressibility of the solid media as well as the simplification facilitated by the incompressibility of the surrounding fluid. The proposed techniques use the traditional idea of selective reduced integration for the solid medium and the more recent idea of perfectly matched discrete layers for the surrounding fluid. Also, used is the recently developed complex-length finite element method for platelike structures. Several numerical examples are presented to illustrate the practicality and effectiveness of the developed techniques in computing shear wave dispersion in a variety of waveguides.
Neuronavigation-guided focused ultrasound for transcranial blood-brain barrier opening and immunostimulation in brain tumors
Authors: Chen Ko-Ting , Chai Wen-Yen , Lin Ya-Jui , Lin Chia-Jung , Chen Pin-Yuan , Tsai Hong-Chieh , Huang Chiung-Yin , Kuo John S. , Liu Hao-Li , Wei Kuo-Chen
Published: February 2021

Focused ultrasound transiently opens the blood-brain barrier and provides the potential to modulate tumor immunostimulatory effect.
Tumor to normal single-cell mRNA comparisons reveal a pan-neuroblastoma cancer cell
Authors: Kildisiute Gerda , Kholosy Waleed M. , Young Matthew D. , Roberts Kenny , Elmentaite Rasa , van Hooff Sander R. , Pacyna Clarissa N. , Khabirova Eleonora , Piapi Alice , Thevanesan Christine , Bugallo-Blanco Eva , Burke Christina , Mamanova Lira , Keller Kaylee M. , Langenberg-Ververgaert Karin P.S. , Lijnzaad Philip , Margaritis Thanasis , Holstege Frank C.P. , Tas Michelle L. , Wijnen Marc H.W.A. , van Noesel Max M. , del Valle Ignacio , Barone Giuseppe , van der Linden Reinier , Duncan Catriona , Anderson John , Achermann John C. , Haniffa Muzlifah , Teichmann Sarah A. , Rampling Dyanne , Sebire Neil J. , He Xiaoling , de Krijger Ronald R. , Barker Roger A. , Meyer Kerstin B. , Bayraktar Omer , Straathof Karin , Molenaar Jan J. , Behjati Sam
Published: February 2021

Neuroblastoma is a childhood cancer that resembles developmental stages of the neural crest. It is not established what developmental processes neuroblastoma cancer cells represent. Here, we sought to reveal the phenotype of neuroblastoma cancer cells by comparing cancer (n= 19,723) with normal fetal adrenal single-cell transcriptomes (n= 57,972). Our principal finding was that the neuroblastoma cancer cell resembled fetal sympathoblasts, but no other fetal adrenal cell type. The sympathoblastic state was a universal feature of neuroblastoma cells, transcending cell cluster diversity, individual patients, and clinical phenotypes. We substantiated our findings in 650 neuroblastoma bulk transcriptomes and by integrating canonical features of the neuroblastoma genome with transcriptional signals. Overall, our observations indicate that a pan-neuroblastoma cancer cell state exists, which may be attractive for novel immunotherapeutic and targeted avenues.
Falling living standards during the COVID-19 crisis: Quantitative evidence from nine developing countries
Authors: Egger Dennis , Miguel Edward , Warren Shana S. , Shenoy Ashish , Collins Elliott , Karlan Dean , Parkerson Doug , Mobarak A. Mushfiq , Fink Günther , Udry Christopher , Walker Michael , Haushofer Johannes , Larreboure Magdalena , Athey Susan , Lopez-Pena Paula , Benhachmi Salim , Humphreys Macartan , Lowe Layna , Meriggi Niccoló F. , Wabwire Andrew , Davis C. Austin , Pape Utz Johann , Graff Tilman , Voors Maarten , Nekesa Carolyn , Vernot Corey
Published: February 2021

Income, employment, and food security fell sharply across low- and middle-income countries during the COVID crisis.
A Randomized Placebo-Controlled Efficacy Study of a Prime Boost Therapeutic Vaccination Strategy in HIV-1-Infected Individuals: VRI02 ANRS 149 LIGHT Phase II Trial
Authors: Lévy Y. , Lacabaratz C. , Lhomme E. , Wiedemann A. , Bauduin C. , Fenwick C. , Foucat E. , Surenaud M. , Guillaumat L. , Boilet V. , Rieux V. , Bouchaud O. , Girard P.-M. , Molina J.-M. , Morlat P. , Hocqueloux L. , Richert L. , Pantaleo G. , Lelièvre J. D. , Thiébaut, R.
Published: February 2021

In this placebo-controlled phase II randomized clinical trial, we evaluated the safety and immunogenicity of a therapeutic prime-boost vaccine strategy using a recombinant DNA vaccine (GTU-MultiHIV B clade) followed by a boost vaccination with a lipopeptide vaccine (HIV-LIPO-5) in HIV-infected patients on combined antiretroviral therapy. We show here that this prime-boost strategy is well tolerated, consistently with previous studies in HIV-1-infected individuals and healthy volunteers who received each vaccine component individually.
Topoisomerase 2β Induces DNA Breaks To Regulate Human Papillomavirus Replication
Authors: Kaminski Paul , Hong Shiyuan , Kono Takeyuki , Hoover Paul , Laimins Laimonis
Published: February 2021

High-risk human papillomaviruses (HPVs) infect epithelial cells and induce viral genome amplification upon differentiation. HPV proteins activate DNA damage repair pathways by inducing high numbers of DNA breaks in both viral and cellular DNAs.
Role of Two Metacaspases in Development and Pathogenicity of the Rice Blast Fungus Magnaporthe oryzae
Authors: Fernandez Jessie , Lopez Victor , Kinch Lisa , Pfeifer Mariel A. , Gray Hillery , Garcia Nalleli , Grishin Nick V. , Khang Chang-Hyun , Orth Kim
Published: February 2021

Magnaporthe oryzae
causes rice blast disease that threatens global food security by resulting in the severe loss of rice production every year. A tightly regulated life cycle allows
M. oryzae
to disarm the host plant immune system during its biotrophic stage before triggering plant cell death in its necrotrophic stage.
Proteome-Wide Analysis of Lysine 2-Hydroxyisobutyrylation in Candida albicans
Authors: Zheng Hailin , Song Nana , Zhou Xiaowei , Mei Huan , Li Dongmei , Li Xiaofang , Liu Weida
Published: February 2021

C. albicans
is one of the most commonly reported fungal pathogens in mucosal and systemic infections. A better understanding of its growth habits and metabolic processes in the host should help improve defense strategies.
Improved quality of reporting safety data of medication in paediatric randomised controlled trials
Authors: Prins Taco Jan , Rollema Corine , van Roon Eric , Vries Tjalling de
Published: February 2021

Objective

Evaluating the reporting of safety data of medication in paediatric randomised controlled trials (RCTs) in 2017–2018 compared with our earlier study.

Design

Literature search with a systemic appraisal of adverse drug event reporting.

Main outcome measures

Quality of reporting of safety data using Consolidated Standards of Reporting Trials (CONSORT) and Ioannidis scores in paediatric drug RCTs. The CONSORT score consists of nine recommendations of the CONSORT Group issued to improve the quality of reporting adverse events. The Ioannidis score is based on these advices. We considered a CONSORT score of at least 6 and an Ioannidis score of at least 3 as sufficient.

Results

We reviewed 100 RCTs published in 2017 and 2018. Ninety-four (94%) articles mentioned adverse events compared with 78% in the earlier study. Fifty-seven per cent used a standardised method for reporting adverse events compared with 34% in our earlier study. In 26 of the articles, the expected adverse events were defined, and 27 articles had a preset standardised scale for adverse events. Of these, 62 articles (62%) had a CONSORT score of 6 or higher compared with 18% in 2010. In the present study, 67% had an Ioannidis score of 3 or higher, whereas in the earlier study this was 29%. Both differences are statistically significant (p<0.05).

Conclusions

Reporting safety data in paediatric RCTs has improved over the past 10 years. However, there is still room for improvement and for further improvement. Authors and editors should give more attention to methods for collecting, reporting and presenting safety data of RCTs in studies and manuscripts.
Aggressive systemic mastocytosis presenting as rapidly progressive ascites, generalised lymphadenopathy and osteosclerosis
Authors: Arun Vijayalakshmi Aravindan , Soni Dipesh , Bal Amanjit , Jain Arihant
Published: February 2021

Rapidly progressive ascites is a frequent clinical manifestation of advanced abdominal malignancies or portal hypertension due to liver diseases. We report a case of 61-year-old man who presented with rapidly progressive ascites. The presence of ascites, generalised lymphadenopathy, osteosclerosis on imaging and hepatosplenomegaly initially pointed towards the diagnosis of advanced high-grade lymphoma or accelerated myeloid neoplasm. Lymph node biopsy revealed infiltration by CD45, cKIT and CD30; tryptase and toluidine blue-positive mast cells (MCs). Bone marrow examination revealed infiltration by MCs and next generation sequencing revealed the pathognomic exon 17 D 816V KIT mutation. The patient was started on weekly pegylated interferon with significant symptom relief. Systemic mastocytosis should be considered as a differential diagnosis in a clinical case of ascites of unknown aetiology even in the absence of typical skin manifestations.
Acute renal transplant rejection following nivolumab therapy for metastatic melanoma
Authors: Tan Brandon , Baxter Mark , Casasola Richard
Published: February 2021

Cancers can develop the ability to evade immune recognition and destruction. Immune checkpoint inhibitors (ICIs) are drugs targeting these immune evasion mechanisms. ICIs have significantly improved outcomes in several cancers including metastatic melanoma. However, data on toxicities associated with allograft transplant recipients receiving ICI is limited. We describe a case of a 71-year-old woman who was diagnosed with metastatic melanoma 13 years after renal transplantation. She was commenced on the ICI nivolumab. She developed acute renal transplant rejection 15 days after administration of the first dose. She continues on haemodialysis but has demonstrated complete oncological response. This case demonstrates the risk of acute renal transplant rejection versus improved oncological outcomes. Patients and clinicians must consider this balance when initiating ICI therapy in allograft transplant recipients. Patients should be fully consented of the potential consequences of acute renal transplant rejection including lifelong dialysis.
Enterococcus faecalisinfective endocarditis arising from chronic rectal prolapse in the setting of spinal cord injury
Authors: De Silva Harendra Maneesha , Hewagama Saliya , Strugnell Neil
Published: February 2021

A 45-year-old man had recurrent presentations with pleuritic chest pain and shortness of breath. Four months prior, he had developed cauda equina syndrome from a spinal epidural abscess in the setting of intravenous drug use, complicated by lasting neurological deficits and a rectal prolapse. On his final presentation, blood cultures taken in the absence of antibiotics grewEnterococcus faecalisfrom multiple sets. A transoesophageal echocardiogram confirmed tricuspid valve endocarditis. He recovered well post-targeted long-term antibiotics. Endoscopy confirmed a chronic rectal prolapse with multiple ulcers and was hypothesised as the source of bacteraemia. He subsequently underwent perineal rectosigmoidectomy. This uncommon sequela of rectal prolapse highlights several issues, including the management of neurogenic bowel dysfunction following spinal cord injury and the importance of early prolapse recognition and management. Finally, appropriate collection of blood cultures and correct use of echocardiography are critical steps in investigating infective endocarditis.
Improvement of transitional care from hospital to home for older patients, the TIGER study: protocol of a randomised controlled trial
Authors: Rimmele Martina , Wirth Jenny , Britting Sabine , Gehr Thomas , Hermann Margit , van den Heuvel Dirk , Kestler Andreas , Koch Thomas , Schoeffski Oliver , Volkert Dorothee , Wingenfeld Klaus , Wurm Susanne , Freiberger Ellen , Sieber Cornel
Published: February 2021

Introduction

In Germany, an efficient and feasible transition from hospital to home for older patients, ensuring continuous care across healthcare settings, has not yet been applied and evaluated. Based on the transitional care model (TCM), this study aims to reduce preventable readmissions of patients ≥75 years of age with a transitional care intervention performed by geriatric-experienced care professionals. The study investigates whether the intervention ensures continuous care during transition and stabilises the care situation of patients at home.

Methods and analyses

Randomised controlled clinical trial, recruiting between 25 April 2018 and 31 December 2019 in one German hospital in the city of Regensburg. The intervention group is supported by care professionals in the transition process from hospital to home for up to 12 months. Based on TCM, the intervention includes an individual care plan according to a patient’s symptoms, risks, needs and values. The plan is advanced in the domestic situation via personal visits and telephone contacts. All necessary care actions regarding, for example, mobility, residence adjustments, or nutrition, are initiated to be executed by ambulant care services, and are monitored, evaluated and adapted if necessary. In supervising the care plan, the care professionals do not administer active care services themselves but coordinate them. Patients and their caregivers are actively engaged in the care planning and execution. In contrast, the control group receives only usual discharge planning in the hospital and usual ambulatory care.

The primary outcome is the all-cause readmission rate assessed using health insurance data within a follow-up of up to 12 months after hospital discharge. Secondary outcomes include care quality, mobility, nutritional and wound situation, and health-related quality of life. They are assessed at baseline, after 1 month, 3 months, 6 months, and at the end of study visit. Additionally, the economic efficiency of the intervention will be evaluated.

Ethics and dissemination

Ethics approval for the trial was obtained from the Ethics Committee of the Friedrich-Alexander-Universität Erlangen-Nürnberg. Results will be published in peer-reviewed, open-access scientific journals and disseminated at national and international research conferences and through public presentations in the geriatric and healthcare community.

Trial registration

ClinicalTrials.gov identifier:NCT03513159.
Implementation of the Moyo fetal heart rate monitor in district hospitals in Bihar, India: a feasibility study
Authors: Oommen Hanna , Ranjan Kunal , Murugesan Sudha , Gore Aboli , Sonthalia Sunil , Ninan Pradeep , Bernitz Stine , Sorbye Ingvil , Lukasse Mirjam
Published: February 2021

Objectives

Globally, half of all stillbirths occur during birth. Detection of fetal distress with fetal heart rate monitoring (FHRM), followed by appropriate and timely management, might reduce fresh stillbirths and neonatal morbidity. This study aimed to investigate the barriers and facilitators for the implementation of Moyo FHRM use in Bihar state, and secondarily, the feasibility of collecting reliable obstetrical and neonatal outcome data to assess the effect of implementation.

Setting

CARE Bihar and the hospital management at four district hospitals (DHs) in Bihar state, each with 6500 to 15 000 deliveries a year, agreed to testing the implementation of Moyo FHRM through a process of meetings, training sessions and collecting data. At each hospital, a clinical training expert was trained to train others, while a clinical assessment facilitator collected data.

Methodology

Observational notes were taken at all training sessions and meetings. Individual interviews (n=4) were conducted with clinical training experts (CTEs) on training experiences and barriers and facilitators for Moyo FHRM implementation. The CTEs recoded field notes in diaries. Descriptive analyses performed on pre-implementation and post-implementation data (n=521) assessed quality and completeness.

Results

Main barriers to implementation of Moyo FHRM were health system and cultural challenges involving (1) existing practices, (2) insufficient human resources, (3) action delays and (4) cultural and local challenges. Another barrier was insufficient involvement of doctors. Facilitators for implementation were easy use of the Moyo FHRM device and adequate training for staff.

Electronic collection of obstetrical data worked well but had substantial missing data.

Conclusion

Health system and cultural challenges are a major constraint to Moyo FHRM implementation in low-resource settings. Improvements at all levels of infrastructure, practices and skills will be critical in busy DHs in Bihar. Full-scale implementation needs doctor-led leadership and ownership. Obstetrical data collection for the purpose of scientific analysis needs to be improved.
Piloting gender-oriented colorectal cancer screening with a faecal immunochemical test: population-based registry study from Finland
Authors: Sarkeala Tytti , Färkkilä Martti , Anttila Ahti , Hyöty Marja , Kairaluoma Matti , Rautio Tero , Voutilainen Markku , Helander Sanni , Jäntti Maija , Lehtinen Milla , Patrikka Lotta , Malila Nea , Heinävaara Sirpa
Published: February 2021

Objective

To assess the feasibility and evaluate the performance of a relaunched colorectal cancer (CRC) screening programme with different cut-offs for men and women.

Design

Population-based registry study.

Setting

Nine municipalities in Finland which started CRC screening with faecal immunochemical test (FIT) in April 2019 with cut-off levels 70 µg Hg/g faeces for men and 25 µg Hg/g faeces for women.

Participants

Men (n=13 059) and women (n=14 669) aged 60–66 years invited to screening during the first programme year.

Outcome measures

Participation rates, positivity rates, detection rates of CRC and advanced adenoma (AA), and positive predictive values (PPV) of FIT for CRC and AA.

Results

Altogether 21 993 invitees returned stool samples. The participation rate of women (83.4%; 95% CI 82.8 to 84.0) was significantly higher than that of men (74.7%; 95% CI 73.9 to 75.4). The positivity rates were 2.4% (2.2 to 2.7) and 2.8% (2.5 to 3.1), respectively. In total, 37 CRCs and 116 AAs were detected. The detection rates of CRC and AA per 1000 participants were 1.8 (1.1 to 2.9) and 7.2 (5.6 to 9.1) for men and 1.6 (0.9 to 2.4) and 3.8 (2.8 to 5.0) for women. The PPVs per 100 positive tests were 6.6 (4.0 to 10.3) and 25.7 (20.6 to 31.4) for men and 6.4 (3.9 to 9.8) and 15.5 (11.6 to 20.2) for women.

Conclusions

The chosen FIT strategy narrowed the gap in the diagnostic performance between men and women especially in the detection of CRC. The participation rates were excellent. The levels of positivity and detection rates were moderate and need further action. The results indicate that gender-specific protocols can be introduced to organised CRC screening. It is yet to be seen whether they are more effective than a uniform screening protocol.
Involvement of community paediatricians in the care of children and young people with mental health difficulties in the UK: implications for case ascertainment by child and adolescent psychiatric, and paediatric surveillance systems
Authors: Ayyash Hani F , Ogundele Michael Oladipo , Lynn Richard M , Schumm Tanja-Sabine , Ani Cornelius
Published: February 2021

Objective

To ascertain the extent to which community paediatricians are involved in the care of children with mental health conditions in order to determine which difficulties are appropriate for single or joint surveillance by the British Paediatric Surveillance Unit (BPSU) and Child and Adolescent Psychiatry Surveillance System (CAPSS).

Design

An online survey of the 1120 members of the British Association of Community Child Health (BACCH) working in 169 Community Child Health (CCH) services in the UK.

Results

A total of 245 community paediatricians responded to the survey. This represents 22% of members of BACCH but likely to have covered many of the 169 CCH units because participants could respond on behalf of other members in their unit. The survey showed that children and young people (CYP) with neurodevelopmental conditions presented more frequently to paediatrics than to Child and Adolescent Mental Health Services (CAMHS). In addition, a sizeable proportion of CYP with emotional difficulties presented to paediatricians (eg, 29.5% for anxiety/obsessive compulsive disorder (OCD), and 12.8% for depression)—mainly due to difficulty with accessing CAMHS. More than half of the community paediatricians are involved in the care of CYP with anxiety and OCD, while 32.3% are involved in the care of those with depression.

Conclusion

There is significant involvement of community paediatricians in the care of CYP with mental health conditions. Involvement is highest for neurodevelopmental conditions, but also significant for CYP with emotional difficulties. The implication of the findings for surveillance case ascertainment is that joint BPSU and CAPSS is recommended for surveillance studies of neurodevelopmental conditions. However, for emotional disorders, single or joint surveillance should be made based on the specific research question and the relative trade-offs between case ascertainment, and the additional cost and reporting burden of joint surveillance. Single CAPSS studies remain appropriate for psychosis and bipolar disorder.
Prostaglandin E2 receptor PTGER4-expressing macrophages promote intestinal epithelial barrier regeneration upon inflammation
Authors: Na Yi Rang , Jung Daun , Stakenborg Michelle , Jang Hyeri , Gu Gyo Jeong , Jeong Mi Reu , Suh Soo Youn , Kim Hak Jae , Kwon Yoon Hey , Sung Tae Sik , Ryoo Seung Bum , Park Kyu Joo , Im Jong Pil , Park Ji Yong , Lee Yun Sang , Han Heonjong , Park Boyoun , Lee Sungwook , Kim Daesik , Lee Ho Su , Cleynen Isabelle , Matteoli Gianluca , Seok Seung Hyeok
Published: February 2021

Objective

Dysfunctional resolution of intestinal inflammation and altered mucosal healing are essential features in the pathogenesis of inflammatory bowel disease (IBD). Intestinal macrophages are vital in the process of inflammation resolution, but the mechanisms underlying their mucosal healing capacity remain elusive.

Design

We investigated the role of the prostaglandin E2 (PGE2) receptor PTGER4 on the differentiation of intestinal macrophages in patients with IBD and mouse models of intestinal inflammation. We studied mucosal healing and intestinal epithelial barrier regeneration in Csf1r-iCre Ptger4fl/fl mice during dextran sulfate sodium (DSS)-induced colitis. The effect of PTGER4+ macrophage secreted molecules was investigated on epithelial organoid differentiation.

Results

Here, we describe a subset of PTGER4-expressing intestinal macrophages with mucosal healing properties both in humans and mice. Csf1r-iCre Ptger4fl/fl mice showed defective mucosal healing and epithelial barrier regeneration in a model of DSS colitis. Mechanistically, an increased mucosal level of PGE2 triggers chemokine (C-X-C motif) ligand 1 (CXCL1) secretion in monocyte-derived PTGER4+ macrophages via mitogen-activated protein kinases (MAPKs). CXCL1 drives epithelial cell differentiation and proliferation from regenerating crypts during colitis. Specific therapeutic targeting of macrophages with liposomes loaded with an MAPK agonist augmented the production of CXCL1 in vivo in conditional macrophage PTGER4-deficient mice, restoring their defective epithelial regeneration and favouring mucosal healing.

Conclusion

PTGER4+ intestinal macrophages are essential for supporting the intestinal stem cell niche and regeneration of the injured epithelium. Our results pave the way for the development of a new class of therapeutic targets to promote macrophage healing functions and favour remission in patients with IBD.
Using synthetic control methodology to estimate effects of aCure Violenceintervention in Baltimore, Maryland
Authors: Buggs Shani A , Webster Daniel W , Crifasi Cassandra K
Published: February 2021

Objective

To estimate the long-term impact of Safe Streets Baltimore, which is based on theCure Violenceoutreach and violence interruption model, on firearm violence.

Methods

We used synthetic control methods to estimate programme effects on homicides and incidents of non-fatal penetrating firearm injury (non-fatal shootings) in neighbourhoods that had Safe Streets’ sites and model-generated counterfactuals. Synthetic control analyses were conducted for each firearm violence outcome in each of the seven areas where Safe Streets was implemented. The study also investigated variation in programme impact over time by generating effect estimates of varying durations for the longest-running programme sites.

Results

Synthetic control models reduced prediction error relative to regression analyses. Estimates of Safe Streets’ effects on firearm violence varied across intervention sites: some positive, some negative and no effect. Beneficial programme effects on firearm violence reported in prior research were found to have attenuated over time.

Conclusions

For highly targeted interventions, synthetic control methods may provide more valid estimates of programme impact than panel regression with data from all city neighbourhoods. This research offers new understanding about the effectiveness of theCure Violenceintervention over extended periods of time in seven neighbourhoods. Combined with existingCure Violenceevaluation literature, it also raises questions about contextual and implementation factors that might influence programme outcomes.
Mesenchymal stem cells and oncolytic viruses: joining forces against cancer
Authors: Moreno Rafael
Published: February 2021

The development of oncolytic viruses (OVs) has increased significantly in the past 20 years, with many candidates entering clinical trials and three of them receiving approval for some indications. Recently, OVs have also gathered interest as candidates to use in combination with immunotherapies for cancer due to their immunogenic properties, which include immunogenic cell death and the possibility to carry therapeutic transgenes in their genomes. OVs transform non-immunogenic ‘cold’ tumors into inflamed immunogenic ‘hot’ tumors, where immunotherapies show the highest efficacy. However, in monotherapy or in combination with immunotherapy, OVs face numerous challenges that limit their successful application, in particular upon systemic administration, such as liver sequestration, neutralizing interactions in blood, physical barriers to infection, and fast clearance by the immune system. In this regard, the use of mesenchymal stem cells (MSCs) as cells carrier for OV delivery addresses many of these obstacles acting as virus carriers and factories, expressing additional transgenes, and modulating the immune system. Here, I review the current progress of OVs-loaded MSCs in cancer, focusing on their interaction with the immune system, and discuss new strategies to improve their therapeutic efficacy.
Neurofilament light chain predicts future dementia risk in cerebral small vessel disease
Authors: Egle Marco , Loubiere Laurence , Maceski Aleksandra , Kuhle Jens , Peters Nils , Markus Hugh S
Published: February 2021

Objectives

Serum neurofilament light chain (NfL) has been proposed as prognostic markers in neurogenerative disease. A cross-sectional study in cerebral small vessel disease (SVD) reported an association with cognition and disability. If NfL is to be used to predict outcome, studies are required to demonstrate baseline NfL predicts future dementia risk. Furthermore, if it is to be used as a surrogate marker in clinical trials, change in NfL over time periods typical of a clinical trial must be linked to clinical progression. In a longitudinal study of patients with lacunar stroke and confluent white matter hyperintensities, we determined whether both baseline, and change, in NfL levels were linked to changes in MRI markers, cognitive decline and dementia risk.

Methods

Patients underwent MRI, cognitive testing and blood taking at baseline and annually for 3 years. Clinical and cognitive follow-up continued for 5 years.

Results

NfL data were available for 113 subjects for baseline analysis, and 90 patients for the longitudinal analysis. Baseline NfL predicted cognitive decline (global cognition β=−0.335, SE=0.094, p=0.001) and risk of converting to dementia (HR=1.676 (95% CI 1.183 to 2.373), p=0.004). In contrast to imaging, there was no change in NfL values over the follow-up period.

Conclusions

Baseline NfL predicts changes in MRI markers, cognitive decline and dementia rate over a 5 years follow-up period in SVD, suggesting NfL may be a useful prognostic marker. However, change in NfL values was not detected, and therefore NfL may not be a useful surrogate marker in clinical trials in SVD.
Within-trial economic analysis of flare data from the BLISS-SC trial of subcutaneous belimumab in systemic lupus erythematosus
Authors: Lokhandwala Tasneem , Yue Binglin , Coutinho Anna D , Bell Christopher F
Published: February 2021

Objective

The management of systemic lupus erythematosus (SLE) flares can incur substantial healthcare costs. In the phase III BLISS-SC trial, subcutaneous (SC) belimumab 200 mg plus standard therapy was associated with significant reductions in time to severe flare, and risk of flares, versus placebo plus standard therapy, in adults with active SLE. We evaluated whether the reduction in SLE flares with belimumab SC plus standard therapy translated to lower healthcare costs.

Methods

A retrospective, post hoc economic analysis of BLISS-SC data was conducted. Unit costs per flare from claims data were estimated and applied to flares observed in BLISS-SC to quantify costs associated with treating severe flares (primary objective) or flares of any severity (secondary objective).

Results

Of 836 patients (n=556 belimumab, n=280 placebo) analysed (94.4% female, mean (standard deviation, SD) age 38.6 (12.3) years), 13.2% and 62.8% had experienced a severe or mild/moderate flare, respectively. Mean (SD) unit costs per severe, moderate, mild or mild/moderate flare were US$9273 (38 800), US$3048 (9321), US$1671 (6202) and US$2303 (7821), respectively. Adjusted mean costs of treating flares were significantly lower with belimumab SC plus standard therapy than placebo plus standard therapy (severe flare, US$927 lower, p<0.001; flare of any severity, US$1379 lower, p<0.001).

Conclusions

This economic analysis of data from the BLISS-SC trial revealed significant cost reductions were associated with treating SLE flares with belimumab SC plus standard therapy versus placebo plus standard therapy. These findings may help to inform decision making about introducing belimumab to healthcare systems.

Trial registration number

NCT01484496.