bluuebunny/crossref_metadata_2025 huggingface dataset:
Blood carnitine profiling on tandem mass spectrometry in liver cirrhotic patients
Authors: Miyaaki Hisamitsu , Kobayashi Hironori , Miuma Satoshi , Fukusima Masanori , Sasaki Ryu , Haraguchi Masafumi , Nakao Kazuhiko
Published: February 2020

Background

The level and profiles of blood free carnitine and acylcarnitines, obtained by acylcarnitine analysis using tandem mass spectrometry, reflect various metabolic conditions. We aimed to examine the level of free carnitine and acylcarnitines in liver cirrhosis patients by acylcarnitine analysis and determine the clinical and subjective factors associated with blood carnitine fraction levels in liver cirrhosis.

Methods

We compared blood carnitine fractions in 54 liver cirrhotic patients to other laboratory test results and questionnaire answers.

Results

In almost all patients, the blood levels of free carnitine (C0) and acetylcarnitine (C2) were within the normal reference range. However, in some patients, the levels of long-chain acylcarnitines, such as C16 and C18:1-acylcarnitine, were higher than the normal reference range. Liver function, assessed by Child-Pugh score, was significantly correlated with the blood level of each carnitine fraction measured (C0, C2, C3, C4, C6, C10, C12, C12:1, C14:1, C16, C18:1, and C18:2-acylcarnitine). Cirrhotic symptom score was significantly correlated with C0, C2, C3, C16, and C18–1-acylcarnitine blood levels. Among the 36-item short-form health survey (SF-36) items, the physical component summary was significantly associated with C0, C2, and C18–1-acylcarnitine blood levels.

Conclusions

Carnitine fraction levels were positively correlated with liver cirrhosis stage, particularly, long-chain acylcarnitines. Moreover, carnitine fraction levels were associated with various subjective physical symptoms in liver cirrhosis patients.
Pain reduction by inducing sensory-motor adaptation in Complex Regional Pain Syndrome (CRPS PRISMA): protocol for a double-blind randomized controlled trial
Authors: Halicka Monika , Vittersø Axel D. , Proulx Michael J. , Bultitude Janet H.
Published: February 2020

Background

Complex Regional Pain Syndrome (CRPS) presents as chronic, continuous pain and sensory, autonomic, and motor abnormalities affecting one or more extremities. People with CRPS can also show changes in their perception of and attention to the affected body part and sensory information in the affected side of space. Prism Adaptation (PA) is a behavioural intervention targeted at reducing attention deficits in post-stroke hemispatial neglect. PA also appears to reduce pain and other CRPS symptoms; however, these therapeutic effects have been demonstrated only in small unblinded studies. This paper describes the protocol for an ongoing double-blind, randomized, sham-controlled clinical trial that will evaluate the efficacy of PA treatment for CRPS. The secondary aims of the study are to examine the relationships between neuropsychological changes (such as spatial attention, space and body representation, and motor spatial performance) and clinical manifestations of CRPS, as well as symptom improvement.

Methods

Forty-two participants with upper-limb CRPS type I will undergo 2 weeks of twice-daily PA treatment or sham treatment. The primary outcome measures are current pain intensity and CRPS severity score, measured immediately before and after the treatment period. Secondary outcome measures include the results of self-report questionnaires about pain, movement, symptoms interference, and body representation; clinical assessments of sensory, motor, and autonomic functions; and computer-based psychophysical tests of neuropsychological functions. Data are collected in four research visits: 4 weeks and 1 day before treatment, and 1 day and 4 weeks after the end of treatment. Additional follow-up through postal questionnaires is conducted 3 and 6 months post-treatment.

Discussion

It is hypothesised that participants undergoing PA treatment, compared to those receiving sham treatment, will show greater reduction in pain and CRPS severity score, and improvements on other clinical and neuropsychological measures. Also, more pronounced neuropsychological symptoms are predicted to correlate with more severe clinical CRPS symptoms. This study will provide the first randomized double-blind evaluation of the therapeutic effects of PA that could be implemented as a rehabilitation method for CRPS, and will contribute to the understanding of how neuropsychological changes in body representation and attention pertain to the manifestation and treatment of CRPS.

Trial registration

(27/03/2017): ISRCTN46828292 (ISRCTN - ISRCTN46828292: Treatment of complex regional pain syndrome (CRPS) with sensory-motor adaptation).
The effect of educational intervention program on promoting preventive behaviors of urinary tract infection in girls: a randomized controlled trial
Authors: Ahmadi Zahra , Shamsi Mohsen , Roozbahani Nasrin , Moradzadeh Rahmatollah
Published: February 2020

Background

Urinary tract infection is one of the most common infectious diseases in children, which can lead to serious complications for a child. The purpose of this study was to investigate the impact of Theory Planned Behavior (TPB) -based education on the promotion of preventive behaviors of urinary tract infection in mothers with a daughter under age two.

Methods

The present study is an educational randomized controlled trial that its sample consisted of 100 mothers who had a daughter under age two. They were selected through convenience sampling and then were randomly assigned to the intervention and control groups (each group included 50 participants). The data collection tool was a reliable and valid questionnaire based on TPB constructs. First, in both groups, the pre-test was administrated and then the educational intervention in the intervention group was conducted in the form of four educational sessions in 1 month (based on the pre-test need assessment) and then 3 months after the intervention (according to the ideas of Panel of Experts), post-test in both groups was administrated and then the data were analyzed through SPSS version 23 software with inferential statistics (independent t-test, paired t-test, and chi-square). The significance level was considered 0.05.

Results

Three months after the intervention, the mean score of the constructs of TPB in the intervention group was significantly higher than the control group. The performance of prevention of urinary tract infection in the intervention group before the education increased from 2.85 ± 0.51 to 3.74 ± 0.29 (out of 4) (p = 0.001).

Conclusions

TPB-based education with active and interventional follow-up was effective in promoting the preventive behaviors of urinary tract infection. Therefore, due to the side effects of UTI, especially in vulnerable periods such as childhood, it is recommended that trainings based on this model be carried out in other health care centers in order to maintain children health.

Trial registration

This trial has been registered at IRCT, IRCT2017031533090N1. Registered on 9 July 2017, https://en.irct.ir/trial/25621
Rehabilitation coordinator intervention versus control in psychiatric specialist care for return to work and reduced sick leave: study protocol of a randomised controlled trial
Authors: Andersén Åsa , Berglund Erik , Anderzén Ingrid
Published: February 2020

Background

Mental disorders are the most common reason for sick leave in Sweden. Knowledge about effective methods to help these individuals to return to work (RTW)/entry into work or studies is limited. Rehabilitation coordinators (RC’s) have been introduced within healthcare with the purpose to promote cooperation, streamline the sick leave and rehabilitation process, and facilitate RTW for sick-listed patients. The function of RC’s has shown positive results by reducing sick leave within primary healthcare. However, the function has not been evaluated in terms of specialist psychiatry. This paper describes the design of a study to evaluate effects of a RC intervention on sick leave and RTW/entry in work or studies in patients with moderate to severe affective and/or moderate to severe anxiety disorders within specialist psychiatric care.

Methods

A randomised controlled trial (RCT) comparing an intervention group receiving support from a RC with a control group receiving treatment as usual (TAU). The target group is patients on sick leave, treated for affective and/or anxiety disorder, aged 25–64, with or without employment.

Discussion

This study gives the possibility to evaluate a RC intervention for individuals with mental disorders. If the study has promising vocational outcomes, it may be of importance for the participants in many ways, e.g. increase participation in society, provide economic benefits and improve health and wellbeing. This would be valuable for the individual as well as for the society.

Trial registration

The study is registered at theClinicaltrials.govRegister Platform (IDNCT03729050) in 2 November 2018.
A probiotic treatment increases the immune response induced by the nasal delivery of spore-adsorbed TTFC
Authors: Santos Francisco Denis S. , Mazzoli Arianna , Maia Ana Raquel , Saggese Anella , Isticato Rachele , Leite Fabio , Iossa Susanna , Ricca Ezio , Baccigalupi Loredana
Published: February 2020

Background

Spore-forming bacteria of the Bacillus genus are widely used probiotics known to exert their beneficial effects also through the stimulation of the host immune response. The oral delivery of B. toyonensis spores has been shown to improve the immune response to a parenterally administered viral antigen in mice, suggesting that probiotics may increase the efficiency of systemic vaccines. We used the C fragment of the tetanus toxin (TTFC) as a model antigen to evaluate whether a treatment with B. toyonensis spores affected the immune response to a mucosal antigen.

Results

Purified TTFC was given to mice by the nasal route either as a free protein or adsorbed to B. subtilis spores, a mucosal vaccine delivery system proved effective with several antigens, including TTFC. Spore adsorption was extremely efficient and TTFC was shown to be exposed on the spore surface. Spore-adsorbed TTFC was more efficient than the free antigen in inducing an immune response and the probiotic treatment improved the response, increasing the production of TTFC-specific secretory immunoglobin A (sIgA) and causing a faster production of serum IgG. The analysis of the induced cytokines indicated that also the cellular immune response was increased by the probiotic treatment. A 16S RNA-based analysis of the gut microbial composition did not show dramatic differences due to the probiotic treatment. However, the abundance of members of the Ruminiclostridium 6 genus was found to correlate with the increased immune response of animals immunized with the spore-adsorbed antigen and treated with the probiotic.

Conclusion

Our results indicate that B. toyonensis spores significantly contribute to the humoral and cellular responses elicited by a mucosal immunization with spore-adsorbed TTFC, pointing to the probiotic treatment as an alternative to the use of adjuvants for mucosal vaccinations.
Hsa_circ_0003159 inhibits gastric cancer progression by regulating miR-223-3p/NDRG1 axis
Authors: Wang Jingyu , Lv Weize , Lin Zhidong , Wang Xiao , Bu Juyuan , Su Yonghui
Published: February 2020

Background

Abnormally expressed circular RNAs (circRNAs) are implicated in the development and treatment of gastric cancer (GC). Previous study has reported that hsa_circ_0003159 is expressed in GC. However, the role and mechanism of hsa_circ_0003159 in GC progression remain unclear.

Methods

GC tissues and normal tissues were harvested from 55 patients in this study. The levels of hsa_circ_0003159, microRNA (miR)-223-3p and N-myc downstream regulated gene 1 (NDRG1) were measured by quantitative real-time polymerase chain reaction or western blot. Cell proliferation, migration, invasion and apoptosis were determined by cell counting kit (CCK)-8, transwell assay, flow cytometry and western blot, respectively. The target association of miR-223-3p-hsa_circ_0003159 and miR-223-3p-NDRG1 was explored by dual-luciferase reporter assay. Xenograft model was established to assess the roles of hsa_circ_0003159 in GC in vivo.

Results

Hsa_circ_0003159 was lowly expressed in GC tissues and cells and mainly presented in the cytoplasm. Low expression of hsa_circ_0003159 was associated with lower overall survival and disease-free survival. Hsa_circ_0003159 overexpression inhibited proliferation, migration and invasion but induced apoptosis in GC cells. MiR-223-3p was a target of hsa_circ_0003159 and abated the effect of hsa_circ_0003159 on proliferation, migration, invasion and apoptosis in GC cells. Hsa_circ_0003159 promoted NDRG1 expression by competitively sponging miR-223-3p. Knockdown of NDRG1 reversed the suppressive effect of hsa_circ_0003159 on GC progression. Besides, hsa_circ_0003159 decreased GC cell xenograft tumor growth by regulating miR-223-3p and NDRG1.

Conclusion

Hsa_circ_0003159 suppressed proliferation, migration, invasion and xenograft tumor growth but promoted apoptosis by decreasing miR-223-3p and increasing NDRG1 in GC, indicating a novel target for treatment of GC.
Establishment and characterization of patient-derived cancer models of malignant peripheral nerve sheath tumors
Authors: Oyama Rieko , Kito Fusako , Takahashi Mami , Hattori Emi , Noguchi Rei , Takai Yoko , Sakumoto Marimu , Qiao Zhiwei , Toki Shunichi , Sugawara Masato , Tanzawa Yoshikazu , Kobayashi Eisuke , Nakatani Fumihiko , Iwata Shintaro , Yoshida Akihiko , Kawai Akira , Kondo Tadashi
Published: February 2020

Background

Malignant peripheral nerve sheath tumors (MPNSTs) are a rare subtype of soft-tissue sarcoma, derived from a peripheral branch or the sheath of the sciatic nerve, brachial plexus, or sacral plexus. The clinical outcomes for MPNST patients with unresectable or metastatic tumors are dismal, and novel therapeutic strategies are required. Although patient-derived cancer cell lines are vital for basic research and preclinical studies, few MPNST cell lines are available from public cell banks. Therefore, the aim of this study was to establish cancer cell lines derived from MPNST patients.

Methods

We used tumor tissues from five patients with MPNSTs, including one derived from a rare bone tissue MPNST. The tumor tissues were obtained at the time of surgery and were immediately processed to establish cell lines. A patient-derived xenograft was also established when a sufficient amount of tumor tissue was available. The characterization of established cells was performed with respect to cell proliferation, spheroid formation, and invasion. The mutation status of actionable genes was monitored by NCC Oncopanel, by which the mutation of 114 genes was assessed by next-generation sequencing. The response to anti-cancer agents, including anti-cancer drugs approved for the treatment of other malignancies was investigated in the established cell lines.

Results

We established five cell lines (NCC-MPNST1-C1, NCC-MPNST2-C1, NCC-MPNST3-C1, NCC-MPNST4-C1, and NCC-MPNST5-C1) from the original tumors, and also established patient-derived xenografts (PDXs) from which one cell line (NCC-MPNST3-X2-C1) was produced. The established MPNST cell lines proliferated continuously and formed spheroids while exhibiting distinct invasion abilities. The cell lines had typical mutations in the actionable genes, and the mutation profiles differed among the cell lines. The responsiveness to examined anti-cancer agents differed among cell lines; while the presence of an actionable gene mutation did not correspond with the response to the anticipated anti-cancer agents.

Conclusion

The established cell lines exhibit various characteristics, including proliferation and invasion potential. In addition, they had different mutation profiles and response to the anti-cancer agents. These observations suggest that the established cell lines will be useful for future research on MPNSTs.
The disease burden attributable to 18 occupational risks in China: an analysis for the global burden of disease study 2017
Authors: Li Jie , Yin Peng , Wang Haidong , Zeng Xinying , Zhang Xiao , Wang Lijun , Liu Jiangmei , Liu Yunning , You Jinling , Zhao Zhenping , Yu Shicheng , Zhou Maigeng
Published: February 2020

Background

China has more than 18% of the global population and over 770 million workers. However, the burden of disease attributable to occupational risks is unavailable in China. We aimed to estimate the burden of disease attributable to occupational exposures at provincial levels from 1990 to 2017.

Methods

We estimated the summary exposure values (SEVs), deaths and disability-adjusted life years (DALYs) attributable to occupational risk factors in China from 1990 to 2017, based on Global Burden of Disease Study (GBD) 2017. There were 18 occupational risks, 22 related causes, and 35 risk-outcome pairs included in this study. Meanwhile, we compared age-standardized death rates attributable to occupational risk factors in provinces of China by socio-demographic index (SDI).

Results

The SEVs of most occupational risks increased from 1990 to 2017. There were 323,833 (95% UI 283,780 - 369,061) deaths and 14,060,210 (12,022,974 - 16,125,763) DALYs attributable to total occupational risks in China, which were 27.9 and 22.1% of corresponding global levels, respectively. For attributable deaths, major risks came from occupational particulate matter, gases, and fumes (PGFs), and for the attributable DALYs, from occupational injuries. The attributable burden was higher in males than in females. Compared with high SDI provinces, low SDI provinces, especially Western China, had higher death rates attributable to total occupational risks, occupational PGFs, and occupational injuries.

Conclusion

Occupational risks contribute to a huge disease burden in China. The attributable burden is higher in males, and in less developed provinces of Western China, reflecting differences in risk exposure, socioeconomic conditions, and type of jobs. Our study highlights the need for further research and focused policy interventions on the health of workers especially for less developed provinces in China to reduce occupational health losses effectively.
Psychometric evaluation of the traditional Chinese version of the resilience Scale-14 and assessment of resilience in Hong Kong adolescents
Authors: Chung Joyce Oi Kwan , Lam Katherine Ka Wai , Ho Ka Yan , Cheung Ankie Tan , Ho Long Kwan , Xei Viveka Wei , Gibson Faith , Li William Ho Cheung
Published: February 2020

Background

A reliable and valid instrument that accurately measures resilience is crucial for the development of interventions to enhance the resilience of adolescents and promote their positive mental well-being. However, there is a lack of adolescent resilience assessment tools with good psychometric properties suitable for use with Hong Kong participants. This study aimed to evaluate the psychometric properties of the traditional Chinese version of the Resilience Scale-14.

Methods

Between October 2017 and January 2018, a stratified random sample of 1816 Grade 7 (aged 11–15 years) students from all 18 districts of Hong Kong were invited to participate in the study. Subjects were asked to respond to the traditional Chinese version of the Resilience Scale-14, the Center for Epidemiologic Studies Depression Scale for children, and Rosenberg’s Self-Esteem Scale. The psychometric properties, including the internal consistency, content validity, convergent and discriminant validity, exploratory and confirmatory factor analyses, and test–retest reliability of the Resilience Scale-14 were assessed.

Results

The translated scale demonstrated good internal consistency and test–retest reliability, excellent content validity, and appropriate convergent and discriminant validity. The results of the confirmatory factor analysis supported the two-factor structure of the traditional Chinese version of the Resilience Scale-14.

Conclusions

Results suggest that the translated scale is a reliable and valid tool to assess the resilience of young Hong Kong Chinese adolescents. Healthcare professionals could use the newly translated scale to assess resilience levels among Hong Kong adolescents and develop interventions that can help them combat mental health problems and lead healthier lives.

Trial registration

Clinicaltrials.gov ID NCT03538145 (retrospectively registered on May 15, 2018).
ADAMTS13 ameliorates inflammatory responses in experimental autoimmune encephalomyelitis
Authors: Lu Kaili , Liu Lan , Xu Xiaofeng , Zhao Fei , Deng Jiangshan , Tang Xin , Wang Xiuzhe , Zhao Bing-Qiao , Zhang Xiaojie , Zhao Yuwu
Published: February 2020

Background

ADAMTS13 (a disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13) plays a vital role in preventing microvascular thrombosis and inflammation. Reduced ADAMTS13 levels in plasma have been detected in multiple sclerosis (MS) patients. In the present study, we have determined the role of ADAMTS13 in the disease progression of MS using a mouse model of experimental autoimmune encephalomyelitis (EAE).

Methods

Female C57BL/6 mice were immunized with MOG35–55 peptide and then treated with ADAMTS13 or vehicle in preventive and therapeutic settings. Mice were analyzed for clinical deficit, white matter demyelination and inflammatory cell infiltration. To explore the underlying mechanism, VWF expression and blood-spinal cord barriers (BSCB) were determined.

Results

Plasma ADAMTS13 activity was suppressed in EAE mice. ADAMTS13-treated EAE mice exhibited an ameliorated disease course, reduced demyelination, and decreased T lymphocyte, neutrophil and monocyte infiltration into the spinal cord. Consistently, ADAMTS13 treatment reduced VWF levels and inhibited BSCB breakdown in the spinal cords of EAE mice. However, leukocytes in the blood and spleen of EAE mice remained unaffected by ADAMTS13 administration.

Conclusion

Our results demonstrate that ADAMTS13 treatment ameliorates inflammatory responses, demyelination and disease course in EAE mice. Therefore, our study suggests that ADAMTS13 may represent a potential therapeutic strategy for MS patients.
A computational model to design neural interfaces for lower-limb sensory neuroprostheses
Authors: Zelechowski Marek , Valle Giacomo , Raspopovic Stanisa
Published: February 2020

Background

Leg amputees suffer the lack of sensory feedback from a prosthesis, which is connected to their low confidence during walking, falls and low mobility. Electrical peripheral nerve stimulation (ePNS) of upper-limb amputee’s residual nerves has shown the ability to restore the sensations from the missing limb via intraneural (TIME) and epineural (FINE) neural interfaces. Physiologically plausible stimulation protocols targeting lower limb sciatic nerve hold promise to induce sensory feedback restoration that should facilitate close-to-natural sensorimotor integration and therefore walking corrections. The sciatic nerve, innervating the foot and lower leg, has very different dimensions in respect to upper-limb nerves. Therefore, there is a need to develop a computational model of its behavior in response to the ePNS.

Methods

We employed a hybrid FEM-NEURON model framework for the development of anatomically correct sciatic nerve model. Based on histological images of two distinct sciatic nerve cross-sections, we reconstructed accurate FEM models for testing neural interfaces. Two different electrode types (based on TIME and FINE) with multiple active sites configurations were tested and evaluated for efficiency (selective recruitment of fascicles). We also investigated different policies of stimulation (monopolar and bipolar), as well as the optimal number of implants. Additionally, we optimized the existing simulation framework significantly reducing the computational load.

Results

The main findings achieved through our modelling study include electrode manufacturing and surgical placement indications, together with beneficial stimulation policy of use. It results that TIME electrodes with 20 active sites are optimal for lower limb and the same number has been obtained for FINE electrodes. To interface the huge sciatic nerve, model indicates that 3 TIMEs is the optimal number of surgically implanted electrodes. Through the bipolar policy of stimulation, all studied configurations were gaining in the efficiency. Also, an indication for the optimized computation is given, which decreased the computation time by 80%.

Conclusions

This computational model suggests the optimal interfaces to use in human subjects with lower limb amputation, their surgical placement and beneficial bipolar policy of stimulation. It will potentially enable the clinical translation of the sensory neuroprosthetics towards the lower limb applications.
Correction to: Effect of vibration characteristics and vibror arrangement on the tactile perception of the upper arm in healthy subjects and upper limb amputees
Authors: Guemann Matthieu , Bouvier Sandra , Halgand Christophe , Paclet Florent , Borrini Leo , Ricard Damien , Lapeyre Eric , Cattaert Daniel , de Rugy Aymar
Published: February 2020

The original article [1] contained an error whereby the captions to Fig. 3 and Fig. 8 were mistakenly interchanged.
Recent advances in human stem cell-based modeling of Tuberous Sclerosis Complex
Authors: Afshar Saber Wardiya , Sahin Mustafa
Published: February 2020

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by epilepsy, intellectual disability, and benign tumors of the brain, heart, skin, and kidney. Animal models have contributed to our understanding of normal and abnormal human brain development, but the construction of models that accurately recapitulate a human pathology remains challenging. Recent advances in stem cell biology with the derivation of human-induced pluripotent stem cells (hiPSCs) from somatic cells from patients have opened new avenues to the study of TSC. This approach combined with gene-editing tools such as CRISPR/Cas9 offers the advantage of preserving patient-specific genetic background and the ability to generate isogenic controls by correcting a specific mutation. The patient cell line and the isogenic control can be differentiated into the cell type of interest to model various aspects of TSC. In this review, we discuss the remarkable capacity of these cells to be used as a model for TSC in two- and three-dimensional cultures, the potential variability in iPSC models, and highlight differences between findings reported to date.
Imaging of mandibular fractures: a pictorial review
Authors: Nardi Cosimo , Vignoli Chiara , Pietragalla Michele , Tonelli Paolina , Calistri Linda , Franchi Lorenzo , Preda Lorenzo , Colagrande Stefano
Published: February 2020

Mandibular fractures are among the most common maxillofacial fractures observed in emergency rooms and are mainly caused by road accidents. The clinical features of mandibular fractures include malocclusion and loss of mandibular function. Panoramic radiography is usually limited to isolated lesions, whereas computed tomography is the tool of choice for all other facial traumatic events. No reference standard classification system for the different types of mandibular fractures is defined. Therapeutic options include a conservative approach or surgical treatment based on the anatomic area and the severity of fracture. The main purpose of this pictorial review is to illustrate a practical description of the pathophysiology of mandibular fractures and describe both the imaging techniques to recognise them and the therapeutic indications.
Transforming growth factor β1 accelerates and enhances in vitro red blood cell formation from hematopoietic stem cells by stimulating mitophagy
Authors: Kuhikar Rutuja , Khan Nikhat , Philip Joseph , Melinkeri Sameer , Kale Vaijayanti , Limaye Lalita
Published: February 2020

Background

Generation of red blood cells (RBCs) from hematopoietic stem cells (HSCs) in vitro takes about 21 days, making it unaffordable for clinical applications. Acceleration of the in vitro erythropoiesis process by using small molecules could eventually make the large-scale production of these cells commercially viable. Transforming Growth Factor β1 (TGF-β1) has been shown to have a dose-dependent activity on the HSCs: at high concentration it inhibits, whereas at low concentration it stimulates the HSCs growth. At high concentration, it also inhibits erythropoiesis but accelerates terminal erythroid differentiation of cell lines and erythroid progenitors. Here we examined whether the use of low concentration of TGF-β1 would be beneficial for increasing RBC production by stimulating HSC growth and also supporting erythroid differentiation. Such a strategy could make RBC production in vitro more efficient and cost-effective for clinical applications.

Methods

HSCs isolated from Apheresis samples were differentiated into mature RBCs by the sequential addition of specific combinations of growth factors for 21 days. In the control set, only EPO (3 IU/ml) was added whereas, in the test set, TGF-β1 at a concentration of 10 pg/ml was added along with EPO (3 IU/ml) from day 0.

Results

We found that a low concentration of TGF-β1 has no inhibitory effect on the proliferation of the early stages of erythropoiesis. Additionally, it significantly accelerates terminal stages of erythroid differentiation by promoting BNIP3L/NIX-mediated mitophagy.

Conclusions

Incorporation of TGF-β1 at 10 pg/ml concentration in the differentiation medium accelerates the in vitro erythropoiesis process by 3 days. This finding could have potential applications in transfusion medicine.
Correction to: Rev1 wbdR tagged vaccines against Brucella ovis
Authors: Aragón‑Aranda Beatriz , de Miguel María Jesús , Martinez‑Gomez Estrella , Zuñiga‑Ripa Amaia , Salvador‑Bescós Miriam , Moriyón Ignacio , Iriarte Maite , Muñoz Pilar M. , Conde‑Alvarez Raquel
Published: February 2020

In the original publication of this article [1], the corresponding author points out Pilar M. Muñoz and Raquel Conde‑Alvarez contributed equally to this work.
Periodicity makes perfect: recovering interfered preamble for high-coexistence wireless systems
Authors: Li Ping , Yang Panlong , Yan Yubo
Published: February 2020

Recent researches show that cross technology interference management plays an important role in the emergence of innovative applications for nowadays wireless networks. Existing algorithms either suffer from the constraint on the need of clean preamble or require technological similarities among cross technology systems. In this paper, we ask the question: “whether the packet with interfered preamble can be decoded?" To answer this question, we investigate the property of preamble and propose Narthil, an innovative coexistence algorithm which based on imperfect interference management, handling packet detection, symbol synchronization, and channel estimation with interfered preambles. Narthil applies a simple Butterworth band-stop filter for imperfect interference filtering, and leverages the residual signals for packet detection and symbol synchronization, as well as channel estimation. The insight is the inherent properties of preamble such as periodicity and modulation scheme, and the frequency continuity in OFDM signal could be effectively leveraged for important processes such as packet detection, symbol synchronization, and channel estimation. These favorable properties could be used to further enhance the performance of other cross technology signal coexistence algorithms. We implement Narthil algorithm on our USRP/GNU Radio platform, and evaluate its performance by using 15 USRP-N210 devices through the real deployment experiments. The results demonstrate that Narthil can effectively detect the incoming packet and achieves a high accuracy symbol synchronization, as well as channel estimation of the interfered preamble, and also achieve a good performance on packet decoding.
Sedentary behaviour in hospitalised older people: a scoping review protocol
Authors: Jasper Unyime S. , Yadav Lalit , Jadczak Agathe Daria , Yu Solomon , Visvanathan Renuka , Dollard Joanne
Published: February 2020

Background

Older adults spend up to 23 h daily sitting or lying while in hospital. Sedentary behaviour (SB) within a hospital setting is often associated with poor health outcomes including physical and cognitive decline, reduced quality of life and death as well as hospital readmissions. Conversely, replacing SB with mild to moderate levels of physical activity such as walking can significantly reduce hospital readmission risk by 30 days. Given the potentially harmful effects of SB in hospitalised older adults, it is vital to identify current literature by broadly exploring different aspects of SB among older people in hospital. The overall aim of this scoping review is to produce a literature map of current evidence on key domains of sedentary behaviour in hospitalised older people.

Method

A search for relevant publications will be undertaken in Pedro, MEDLINE Ovid, Cochrane, Scopus, Cumulative Index to Nursing and Allied Health Literature, PsychInfo, Embase, Ageline, Joanna Briggs Institute (JBI) and clinical trials registries. Publications in English and those where the author can provide the full text in English will be included. Studies conducted in hospitals (including in-patient rehabilitation facilities) or acute and subacute care settings and in people aged ≥ 65 will be included. A three-stage method will be used to identify relevant articles, consisting of database search using keywords, keywords and index words across all databases, and reference searching. Articles will be selected following screening of titles/abstracts succeeded by a full-text appraisal utilising a standardised selection form. Two independent reviewers will extract data using the standardised form that will be tested on two articles. A narrative summary will accompany results presented in tables and figures.
How to achieve the climate targets? Spatial planning in the context of the German energy transition
Authors: Wiehe Julia , von Haaren Christina , Walter Anna
Published: February 2020

Background

The transition of the energy system to renewable energy depends on how successfully the national objectives can be implemented at the lower planning levels. Germany pursues an incentive-oriented policy that is not spatially targeted and lets regional and local stakeholders determine where and how renewable energies are used.

A core question is how to achieve the national goals, in a federal system that allows freedom of planning for the local communities. The aim of this paper is to show the discrepancies between the current expansion of wind energy and the necessary expansion that is derived from a scientific analysis.

Methods

The study examined the policy objectives for the expansion of wind energy, based on a literature analysis. In a second step, the regulatory competences and spatial planning at the various levels and their influence on the expansion were explored. In a third step, the current procedure was compared with scientific scenarios of the energy system in 2050 and concretized using the example of the Hannover Region.

Results

The theoretical and empirical analysis shows that people at regional level underestimate their responsibility for contributing to energy transition. The expansion targets for wind energy in the Hannover Region projected in the scientific scenario are above the minimum demand that the local authorities have assumed. The same applies to the state of Lower Saxony, which underestimates its own wind energy potential and thus its necessary contribution to achieving the national targets.

Conclusions

We propose a nationwide coordinated strategy for the successful implementation of the energy transition. With the methodology described, regional targets can be determined and the responsibility of the region and the local actors can be clarified. With the help of spatial planning and public participation, the energy transition can be achieved with this approach.
Carbapenemase-producing Enterobacteriaceae circulating in the Reunion Island, a French territory in the Southwest Indian Ocean
Authors: Miltgen Guillaume , Cholley Pascal , Martak Daniel , Thouverez Michelle , Seraphin Paul , Leclaire Alexandre , Traversier Nicolas , Roquebert Bénédicte , Jaffar-Bandjee Marie-Christine , Lugagne Nathalie , Cimon Céline Ben , Ramiandrisoa Mahery , Picot Sandrine , Lignereux Anne , Masson Geoffrey , Allyn Jérôme , Allou Nicolas , Mavingui Patrick , Belmonte Olivier , Bertrand Xavier , Hocquet Didier
Published: February 2020

Background

The spread of carbapenemase-producing Enterobacteriaceae (CPE) in the Southwest Indian Ocean area (SIOA) is poorly documented. Reunion Island is a French overseas territory located close to Madagascar and connected with Southern Africa, Indian sub-continent and Europe, with several weekly flights. Here we report the results of the CPE surveillance program in Reunion Island over a six-year period.

Methods

All CPE were collected between January 2011 and December 2016. Demographics and clinical data of the carrier patients were collected. We determined their susceptibility to antimicrobials, identified the carbapenemases and ESBL by PCR and sequencing, and explored their genetic relationship using pulsed-field gel electrophoresis and multi-locus sequence typing.

Results

A total of 61 CPEs isolated from 53 patients were retrieved in 6 public or private laboratories of the island. We found that 69.8% of CPE patients were linked to a foreign country of SIOA and that almost half of CPE cases (47.2%) reached the island through a medical evacuation. The annual number of CPE cases strongly increased over the studied period (one case in 2011 vs. 21 cases in 2016). A proportion of 17.5% of CPE isolates were non-susceptible to colistin. blaNDM was the most frequent carbapenemase (79.4%), followed by blaIMI (11.1%), and blaIMP-10 (4.8%). Autochtonous CPE cases (30.2%) harboured CPE isolates belonging to a polyclonal population.

Conclusions

Because the hospital of Reunion Island is the only reference healthcare setting of the SIOA, we can reasonably estimate that its CPE epidemiology reflects that of this area. Mauritius was the main provider of foreign CPE cases (35.5%). We also showed that autochthonous isolates of CPEs are mostly polyclonal, thus unrelated to cross-transmission. This demonstrates the local spread of carbapenemase-encoding genes (i.e. blaNDM) in a polyclonal bacterial population and raises fears that Reunion Island could contribute to the influx of NDM-carbapenemase producers into the French mainland territory.
Perception of quality of life in people experiencing or having experienced a Clostridioides difficile infection: a US population survey
Authors: Lurienne Lise , Bandinelli Pierre-Alain , Galvain Thibaut , Coursel Charles-Alexis , Oneto Caterina , Feuerstadt Paul
Published: February 2020

Background

Although the incidence, severity and mortality of Clostridioides (Clostridium) difficile infection (CDI) have been increasing, patients’ quality of life changes resulting from CDI have not been studied thoroughly. This study aimed at exploring the consequences of CDI on quality of life through patients’ perspective.

Methods

An observational, cross-sectional study involving 350 participants with a self-reported CDI diagnosis was conducted through an online self-administered survey. Participants were grouped into those who had active disease (“Current CDI”) and those who had a history of CDI (“Past CDI”).

Results

One hundred fifteen participants (33%) reported Current CDI and 235 (67%) reported Past CDI. A large majority of participants admitted that their daily activities were impacted by the infection (93.9% and 64.7% of Current and Past CDI respondents respectively, p < 0.05). Physical and psychological consequences of CDI were experienced by 63.5% and 66.1% of participants with active CDI. Despite the infection being cleared, these consequences were still frequently experienced in Past CDI cohort with similar rates (reported by 73.2% of respondents for both, physical consequences p = 0.08; psychological consequences p = 0.21). After the infection, 56.6% of respondents noted that post-CDI symptoms remained; 40.9% believed they would never get rid of them.

Conclusions

While the societal burden of CDI is well described in the literature, our study is one of the first aimed at understanding the major burden of CDI on quality of life. Our results highlight the long-lasting nature of CDI and further reinforce the need for enhanced therapeutics in the prevention and treatment of this devastating infection.
KEYNOTE-365 cohort B updated results: Pembrolizumab (pembro) plus docetaxel and prednisone in abiraterone (abi) or enzalutamide (enza)-pretreated patients (pts) with metastatic castrate-resistant prostate cancer (mCRPC).
Authors: Kolinsky Michael Paul , Gravis Gwenaelle , Mourey Loic , Piulats Josep M. , Sridhar Srikala S. , Romano Emanuela , Berry William R. , Gurney Howard , Retz Margitta , Appleman Leonard Joseph , Boegemann Martin , De Bono Johann S. , Joshua Anthony M. , Emmenegger Urban , Conter Henry Jacob , Laguerre Brigitte , Wu Helen , Schloss Charles , Poehlein Christian Heinrich , Yu Evan Y.
Published: February 2020

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Background: KEYNOTE-365 (NCT02861573) is a phase 1b/2 study to evaluate pembro in combination with other agents in mCRPC. Here we report updated results from cohort B (pembro + docetaxel and prednisone). Methods: Cohort B enrolled pts who failed or were intolerant to ≥4 wk of abi or enza in the prechemotherapy mCRPC state and whose disease progressed within 6 mo of screening as determined by PSA progression or radiologic bone/soft tissue progression. Pts received pembro 200 mg IV + docetaxel 75 mg/m2 IV Q3W and prednisone 5 mg orally twice daily. Primary end points were safety, PSA response rate (confirmed PSA decrease >50%), and ORR per blinded independent central review (BICR). Results: Of 104 treated pts, 72 discontinued, primarily due to progression (55%). Median age was 68 y (range 50-86), 24% were PD-L1+, 25% had visceral disease, and 50% had measurable disease. Median follow-up was 13 mo for all pts (n=104) and 19 mo for pts who had ≥27 wk of follow up (n=72). See table for efficacy outcomes. Treatment-related AEs occurred in 100 pts (96%); most frequent (≥30%) were alopecia, diarrhea, and fatigue (39% each). Grade 3-5 treatment-related AEs occurred in 42 pts (40%). Five pts died of AEs; 2 deaths were from treatment-related AEs (pneumonitis). Conclusions: With additional follow-up, pembro + docetaxel and prednisone continued to show activity in pts with mCRPC who failed previous antihormonal therapy. Safety of the combination was consistent with the known profiles of the individual agents and will be further evaluated in a phase 3 study (KEYNOTE-921). Clinical trial information: NCT02861573. [Table: see text]
PSA progression compared to radiographic or clinical progression in metastatic castration-resistant prostate cancer patients treated with enzalutamide.
Authors: Gandhy Shruti U. , Karzai Fatima , Marte Jennifer L. , Bilusic Marijo , McMahon Sheri , Strauss Julius , Couvillon Anna , Williams Monique , Hankin Amy , Steinberg Seth M. , Figg William Douglas , Arlen Philip M. , Dahut William L. , Gulley James L. , Madan Ravi Amrit
Published: February 2020

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Background: Enzalutamideis ahighly effective treatment in patients with metastatic castration resistant prostate cancer (mCRPC). Although Prostate Cancer Working Group Guidelines (PCWG) recommend continuing treatment until radiographic progression of disease (rPD) or clinical progression (cPD), many patients discontinue therapy for rising PSA alone. Methods: We conducted an open label, randomized phase 2 clinical trial in mCRPC patients (on testosterone suppression therapy) previously untreated with docetaxel, abiraterone, or enzalutamide, comparing enzalutamide alone or in combination with PROSTVAC, a therapeutic cancer vaccine designed to induce an anti-tumor immune response. The study discontinued accrual after a planned interim analysis indicated no difference in progression between the two arms. Patients were followed beyond PSA progression (first of three confirmed PSA rises, evaluated monthly) until rPD per PCWG (scans done every 3 months per protocol). Results: A total of 57 patients were enrolled with a median follow up time of 55.4 months. Of those, 47 (82%) patients were Caucasian and seven (12%) patients were African American. The median age of patients on enrollment was 67.2 years. 49/57 (86%) patients had PSA progression and the median time to first PSA rise for all 57 patients combined was 6.4 months (95% CI: 3.7-11.0 months) after starting enzalutamide. 38/57 (67%) patients experienced progressive disease (majority with rPD and 1/38 (3%) with cPD), with the median time to progression for all 57 patients of 23.3 months (95% CI: 16.1-27.8 months). Conclusions: Consistent with PCWG recommendations, these data suggest that a rising PSA may not be a warning of near-term clinically significant disease progression in mCRPC patients given the nearly 17-month difference between the first rise in PSA and ultimate rPD or cPD seen in this analysis. These data highlight the need to continue to educate patients and providers on PCWG criteria for progression, which were also used in original trials that led to the FDA approval of enzalutamide, so as not to substantially limit the potential efficacy of mCRPC therapies such as enzalutamide. Clinical trial information: NCT01867333.
PROfound: Efficacy of olaparib (ola) by prior taxane use in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) and homologous recombination repair (HRR) gene alterations.
Authors: De Bono Johann S. , Fizazi Karim , Saad Fred , Shore Neal D. , Roubaud Guilhem , Ozguroglu Mustafa , Penel Nicolas , Matsubara Nobuaki , Mehra Niven , Procopio Giuseppe , Kolinsky Michael Paul , Nishimura Kazuo , Feyerabend Susan , Joung Jae Young , Vogelzang Nicholas J. , Carducci Michael Anthony , Kang Jinyu , Poehlein Christian Heinrich , Wu Wenting , Hussain Maha H. A.
Published: February 2020

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Background: Optimal sequencing of therapies for mCRPC is not established. In the Phase III PROfound study (NCT02987543), ola significantly prolonged radiographic progression-free survival (rPFS) vs physician’s choice of new hormonal agent (pcNHA) in pts with mCRPC and an alteration in genes with a direct or indirect role in HRR. We report exploratory subgroup analyses by prior taxane (yes vs no). Methods: Men with mCRPC that had progressed on prior NHA were randomized to ola (tablets; 300 mg bid) or pcNHA (enzalutamide or abiraterone). Pts had alterations in BRCA1, BRCA2 or ATM (Cohort A) or ≥1 of 12 other prespecified genes with a direct or indirect role in HRR (Cohort B). Stratification factors were prior taxane use and measurable disease. rPFS was assessed by blinded independent central review with RECIST v1.1 + PCWG3. Results: Subgroup analyses of rPFS and overall survival (OS) favored ola vs pcNHA irrespective of prior taxane in Cohort A, Cohorts A+B and pts with a BRCA1 and/or BRCA2 or CDK12 alteration (Table). In the ATM subgroup hazard ratio (HR) point estimates for rPFS and OS were lower in pts who had received prior taxane vs pts who had not, but 95% CIs overlapped and pt numbers were small so data should be interpreted with caution. Conclusions: The benefit of ola over pcNHA in pts with mCRPC and HRR gene alterations was generally independent of prior taxane status in the overall study population. Clinical trial information: NCT02987543. [Table: see text]