bluuebunny/crossref_metadata_2025 huggingface dataset:
Asiaticoside inhibits TGF-β1-induced mesothelial-mesenchymal transition and oxidative stress via the Nrf2/HO-1 signaling pathway in the human peritoneal mesothelial cell line HMrSV5
Authors: Zhao Junyi , Shi Jun , Shan Yun , Yu Manshu , Zhu Xiaolin , Zhu Yilin , Liu Li , Sheng Meixiao
Published: May 2020

Background

Peritoneal fibrosis (PF) is a frequent complication caused by peritoneal dialysis (PD). Peritoneal mesothelial cells (PMCs), the first barrier of the peritoneum, play an important role in maintaining structure and function in the peritoneum during PD. Mesothelial-mesenchymal transition (MMT) and oxidative stress of PMCs are two key processes of PF.

Purpose

To elucidate the efficacy and possible mechanism of asiaticoside inhibition of MMT and ROS generation in TGF-β1-induced PF in human peritoneal mesothelial cells (HPMCs).

Methods

MMT and ROS generation of HPMCs were induced by TGF-β1. To explain the anti-MMT and antioxidant role of asiaticoside, varied doses of asiaticoside, oxygen radical scavenger (NAC), TGF-β receptor kinase inhibitor (LY2109761) and Nrf2 inhibitor (ML385) were used separately. Immunoblots were used to detect the expression of signaling associated proteins. DCFH-DA was used to detect the generation of ROS. Transwell migration assay and wound healing assay were used to verify the capacity of asiaticoside to inhibit MMT. Immunofluorescence assay was performed to observe the subcellular translocation of Nrf2 and expression of HO-1.

Results

Asiaticoside inhibited TGF-β1-induced MMT and suppressed Smad signaling in a dose-dependent manner. Migration and invasion activities of HPMCs were decreased by asiaticoside. Asiaticoside decreased TGF-β1-induced ROS, especially in a high dose (150 μM) for 6 h. Furthermore, ML385 partly abolished the inhibitory effect of asiaticoside on MMT, ROS and p-Smad2/3.

Conclusions

Asiaticoside inhibited the TGF-β1-induced MMT and ROS via Nrf2 activation, thus protecting the peritoneal membrane and preventing PF.
The relationship between biological function and teleology: Implications for biology education
Authors: Trommler Friederike , Hammann Marcus
Published: May 2020

This paper explicates the relationship between biological function and teleology by focusing not only on difference but also on conceptual overlap. By doing so, this paper is meant to increase awareness of the misleading potential of biological function and the educational necessity to explicate the meaning of biological function to biology students to prevent them from drawing inadequate teleological conclusions about biological phenomena. The conceptual overlap between teleology and biological function lies in the notion oftelos(end, goal). Biologically inadequate teleology assumes thatteloi(ends, goals) exist in nature and that natural mechanisms are directed towardsteloi. Such inadequate teleological assumptions have been documented in students’ reasoning about biological phenomena. Biological function, however, does not involve the assumption thatteloiexist in nature. Rather, biologists use the notion oftelosas anepistemological toolwhenever they consider a structure or mechanism functional because they view this structure or mechanism as a means to an end (telos). Whereas for biologists such means-ends conceptualizations represent a productive tool for identifying biological phenomena functionally, for students, such means-ends considerations can be misleading. Therefore, this paper explicates how far the concept of biological function involves reference to ends (teloi) and how it relates to biological mechanisms. The paper draws implications on how to prevent students from slipping from functional reasoning into inadequate teleological reasoning.
Schizophyllum commune induced oxidative stress and immunosuppressive activity in Spodoptera litura
Authors: Kaur Mandeep , Chadha Pooja , Kaur Sanehdeep , Kaur Amarjeet , Kaur Rajvir
Published: May 2020

Background

In the last few decades, considerable attention has been paid to fungal endophytes as biocontrol agents, however little is known about their mode of action. This study aimed to investigate the toxic effects of an endophytic fungus Schizophyllum commune by analyzing activities of antioxidant and detoxifying enzymes as well as morphology of haemocytes using Spodoptera litura as a model.

Results

Ethyl acetate extract of S. commune was fed to the larvae of S. litura using the artificial diet having 276.54 μg/ml (LC50 of fungus) concentration for different time durations. Exposed groups revealed significant (p ≤ 0.05) increase in the activities of various enzymes viz. Catalase, Ascorbate peroxidase, Superoxide dismutase, Glutathione-S-Transferase. Furthermore, haemocytes showed various deformities like breakage in the cell membrane, cytoplasmic leakage and appearance of strumae in the treated larvae. A drastic reduction in the percentage of normal haemocytes was recorded in the treated groups with respect to control.

Conclusion

The study provides important information regarding the oxidative stress causing and immunosuppressant potential of S. commune against S. litura and its considerable potential for incorporation in pest management programs.
Association of aortic valve calcification with carotid artery lesions and peripheral artery disease in patients with chronic kidney disease: a cross-sectional study
Authors: Arita Yui , Nakayama Masaru , Matsukuma Yuta , Yoshitomi Ryota , Seki Makiko , Fukui Akiko , Tsuda Susumu , Sonoda Yuri , Imazu Rina , Arakawa Kimika , Tominaga Mitsuhiro , Nakano Toshiaki , Tsuruya Kazuhiko , Kitazono Takanari
Published: May 2020

Background

Patients with chronic kidney disease (CKD) reportedly have a high prevalence of aortic valve calcification (AVC). In population-based studies, AVC is considered a manifestation of systemic atherosclerosis. The association of AVC with atherosclerotic lesions has not been fully investigated in predialysis patients. The present study was performed to determine whether carotid artery lesions and peripheral artery disease (PAD) are associated with AVC in patients with CKD not on dialysis.

Methods

In total, 749 patients were included in this cross-sectional study. AVC was evaluated using echocardiography. Carotid artery lesions including carotid artery plaque (CAP) and PAD were simultaneously examined in each patient. A logistic regression analysis was applied to determine the factors associated with AVC.

Results

AVC, CAP, and PAD were found in 201, 583, and 123 patients, respectively. In the multivariable analyses adjusted for covariates including the estimated glomerular filtration rate and makers of mineral metabolism (serum calcium, serum phosphorus, parathyroid hormone, 1,25-dihydroxyvitamin D, and fibroblast growth factor 23), AVC was significantly associated with the presence of CAP [odds ratio (OR), 3.37; 95% confidence interval (CI), 1.43–7.95], the presence of PAD (OR, 1.76; 95% CI, 1.10–2.81), the CAP score (per 1.0-point increase) (OR, 1.06; 95% CI, 1.02–1.11), and the ankle-brachial blood pressure index (per 0.1-point increase) (OR, 0.83; 95% CI, 0.72–0.95).

Conclusions

AVC was associated with atherosclerotic lesions independent of kidney function and mineral metabolism. We consider that this association between AVC and atherosclerosis might reflect the burden of shared atherosclerotic risk factors.
Effectiveness of a theory-based back care intervention on spine-related behavior among pupils: a school-based randomised controlled trial (T-Bak study)
Authors: Akbari-Chehrehbargh Zahra , Tavafian Sedigheh Sadat , Montazeri Ali
Published: May 2020

Background

Children’s health and welfare have a special place in research and policy in many countries. One of the most important concerns is the increasing rate of backache in children due to many of behavioral risk factors. The aim of this study was to evaluate the effectiveness of an educational program on promoting back-related behavior as well as knowledge, skills, beliefs, and self-efficacy among fifth grade girls.

Methods

The theory-based back care (T-Bak) study was a school-based randomised controlled trial (RCT) that assessed the effectiveness of developing a back care training program based on the social cognitive theory (SCT). A total of 104 schoolchildren aged 11 ± 1.0 years were assigned to intervention (n = 52) and control (n = 52) groups. The intervention group received six sessions training on proper lifting and carrying techniques, having proper posture during daily activities, and correct backpack wearing techniques with a 1-week interval while the control group received nothing. Then, the two groups were assessed for knowledge, skills, self-efficacy, beliefs, and behavior at four points in time: baseline, immediate, three and six-months post-intervention. The changes of the outcomes investigated using univariate repeated measures analysis of variance. Partial eta squared measure (ηp2) was used to calculate effect sizes.

Results

A positive change was found for the intervention group back-related behavior from baseline to immediate post-intervention and follow-ups (F = 78.865, p < 0.001, ηp2 = 0.22). Overall there were 36.4% improvement for knowledge (ηp2 = 0.21), 53.2% for the skills (ηp2 = 0.25), 19.5% for the self-efficacy (ηp2 = 0.11), and 25.6% for the beliefs (ηp2 = 0.14) scores from baseline to 6 months’ follow-up assessments among the intervention group (p < 0.001). The results also showed a significant interaction effect between group and time.

Conclusion

The T-Bak intervention was effective in improving back-related behavior in pupils. It is now available and could be evaluated further in back-care related studies.

Trial registration

Current Controlled Trials IRCT20180528039885N1, 30th Oct 2018, ‘Prospectively registered’. https://www.irct.ir/trial/31534
Addressing the quality and scope of paediatric primary care in South Africa: evaluating contextual impacts of the introduction of the Practical Approach to Care Kit for children (PACK Child)
Authors: Murdoch Jamie , Curran Robyn , Cornick Ruth , Picken Sandy , Bachmann Max , Bateman Eric , Simelane Makhosazana Lungile , Fairall Lara
Published: May 2020

Background

Despite significant reductions in mortality, preventable and treatable conditions remain leading causes of death and illness in children in South Africa. The PACK Child intervention, comprising clinical decision support tool (guide), training strategy and health systems strengthening components, was developed to expand on WHO’s Integrated Management of Childhood Illness programme, extending care of children under 5 years to those aged 0–13 years, those with chronic conditions needing regular follow-up, integration of curative and preventive measures and routine care of the well child. In 2017–2018, PACK Child was piloted in 10 primary healthcare facilities in the Western Cape Province. Here we report findings from an investigation into the contextual features of South African primary care that shaped how clinicians delivered the PACK Child intervention within clinical consultations.

Methods

Process evaluation using linguistic ethnographic methodology which provides analytical tools for investigating human behaviour, and the shifting meaning of talk and text within context. Methods included semi-structured interviews, focus groups, ethnographic observation, audio-recorded consultations and documentary analysis. Analysis focused on how mapped contextual features structured clinician-caregiver interactions.

Results

Primary healthcare facilities demonstrated an institutionalised orientation to minimising risk upheld by provincial documentation, providing curative episodic care to children presenting with acute symptoms, and preventive care including immunisations, feeding and growth monitoring, all in children 5 years or younger. Children with chronic illnesses such as asthma rarely receive routine care. These contextual features constrained the ability of clinicians to use the PACK Child guide to facilitate diagnosis of long-term conditions, elicit and manage psychosocial issues, and navigate use of the guide alongside provincial documentation.

Conclusion

Our findings provide evidence that PACK Child is catalysing a transition to an approach that strikes a balance between assessing and minimising risk on the day of acute presentation and a larger remit of care for children over time. However, optimising success of the intervention requires reviewing priorities for paediatric care which will facilitate enhanced skills, knowledge and deployment of clinical staff to better address acute illnesses and long-term health conditions of children of all ages, as well as complex psychosocial issues surrounding the child.
Quantitative CT-based structural alterations of segmental airways in cement dust-exposed subjects
Authors: Kim Taewoo , Cho Hyun Bin , Kim Woo Jin , Lee Chang Hyun , Chae Kum Ju , Choi So-Hyun , Lee Kyeong Eun , Bak So Hyeon , Kwon Sung Ok , Jin Gong Yong , Choi Jiwoong , Park Eun-Kee , Lin Ching-Long , Hoffman Eric A. , Choi Sanghun
Published: May 2020

Background

Dust exposure has been reported as a risk factor of pulmonary disease, leading to alterations of segmental airways and parenchymal lungs. This study aims to investigate alterations of quantitative computed tomography (QCT)-based airway structural and functional metrics due to cement-dust exposure.

Methods

To reduce confounding factors, subjects with normal spirometry without fibrosis, asthma and pneumonia histories were only selected, and a propensity score matching was applied to match age, sex, height, smoking status, and pack-years. Thus, from a larger data set (N = 609), only 41 cement dust-exposed subjects were compared with 164 non-cement dust-exposed subjects. QCT imaging metrics of airway hydraulic diameter (Dh), wall thickness (WT), and bifurcation angle (θ) were extracted at total lung capacity (TLC) and functional residual capacity (FRC), along with their deformation ratios between TLC and FRC.

Results

In TLC scan, dust-exposed subjects showed a decrease of Dh (airway narrowing) especially at lower-lobes (p < 0.05), an increase of WT (wall thickening) at all segmental airways (p < 0.05), and an alteration of θ at most of the central airways (p < 0.001) compared with non-dust-exposed subjects. Furthermore, dust-exposed subjects had smaller deformation ratios of WT at the segmental airways (p < 0.05) and θ at the right main bronchi and left main bronchi (p < 0.01), indicating airway stiffness.

Conclusions

Dust-exposed subjects with normal spirometry demonstrated airway narrowing at lower-lobes, wall thickening at all segmental airways, a different bifurcation angle at central airways, and a loss of airway wall elasticity at lower-lobes. The airway structural alterations may indicate different airway pathophysiology due to cement dusts.
A demonstration of high field-of-view stability in hands-free echocardiography
Authors: Sjoerdsma Marloes , Fixsen Louis S , Schoots Thijs , van de Vosse Frans N , Lopata Richard GP
Published: May 2020

Background

Exercise stress echocardiography is clinically used to assess cardiovascular diseases. For accurate cardiac evaluation, a stable field-of-view is required. However, transducer orientation and position are difficult to preserve. Hands-free acquisitions might provide more consistent and reproducible results. In this study, the field-of-view stability and variability of hands-free acquisitions are objectively quantified in a comparison with manually obtained images, based on image structural and feature similarities. In addition, the feasibility and consistency of hands-free strain imaging is assessed.

Methods

In twelve healthy males, apical and parasternal images were acquired hands-free, using a fixation device, and manually, during semi-supine exercise sessions. In the final ten seconds of every exercise period, the image structural similarity and cardiac feature consistency were computed using a steerable pyramid employing complex, oriented wavelets. An algorithm discarding images displaying lung artifacts was created. Hands-free strain consistency was analyzed.

Results

Hands-free acquisitions were possible in 9 of the 12 subjects, whereas manually 10 out of 12 could be imaged. The image structural similarity was significantly improved in the hands-free apical window acquisitions (0.91 versus 0.82), and at least equally good in the parasternal window (0.90 versus 0.82). The change in curvature and orientation of the interventricular septum also appeared to be lower in the hands-free acquisitions. The variability in field-of-view was similar in both acquisitions. Longitudinal, septal strain was shown to be at least as consistent when obtained hands-free compared to manual acquisitions.

Conclusions

The field-of-view was shown to be more or equally stable and consistent in the hands-free data in comparison to manually obtained images. The variability was similar, thus respiration- and exercise-induced motions were comparable for manual and hands-free acquisitions. Additionally, the feasibility of hands-free strain has been demonstrated. Furthermore, the results suggest the hands-free measurements to be more reproducible, though further analysis is required.
MR-guided proton therapy: a review and a preview
Authors: Hoffmann Aswin , Oborn Bradley , Moteabbed Maryam , Yan Susu , Bortfeld Thomas , Knopf Antje , Fuchs Herman , Georg Dietmar , Seco Joao , Spadea Maria Francesca , Jäkel Oliver , Kurz Christopher , Parodi Katia
Published: May 2020

Background

The targeting accuracy of proton therapy (PT) for moving soft-tissue tumours is expected to greatly improve by real-time magnetic resonance imaging (MRI) guidance. The integration of MRI and PT at the treatment isocenter would offer the opportunity of combining the unparalleled soft-tissue contrast and real-time imaging capabilities of MRI with the most conformal dose distribution and best dose steering capability provided by modern PT. However, hybrid systems for MR-integrated PT (MRiPT) have not been realized so far due to a number of hitherto open technological challenges. In recent years, various research groups have started addressing these challenges and exploring the technical feasibility and clinical potential of MRiPT. The aim of this contribution is to review the different aspects of MRiPT, to report on the status quo and to identify important future research topics.

Methods

Four aspects currently under study and their future directions are discussed: modelling and experimental investigations of electromagnetic interactions between the MRI and PT systems, integration of MRiPT workflows in clinical facilities, proton dose calculation algorithms in magnetic fields, and MRI-only based proton treatment planning approaches.

Conclusions

Although MRiPT is still in its infancy, significant progress on all four aspects has been made, showing promising results that justify further efforts for research and development to be undertaken. First non-clinical research solutions have recently been realized and are being thoroughly characterized. The prospect that first prototype MRiPT systems for clinical use will likely exist within the next 5 to 10 years seems realistic, but requires significant work to be performed by collaborative efforts of research groups and industrial partners.
On the pitfalls of PTV in lung SBRT using type-B dose engine: an analysis of PTV and worst case scenario concepts for treatment plan optimization
Authors: Leung Ronnie Wing King , Chan Mark Ka Heng , Chiang Chi-Leung , Wong Matthew , Blanck Oliver
Published: May 2020

Background

PTV concept is presumed to introduce excessive and inconsistent GTV dose in lung stereotactic body radiotherapy (SBRT). That GTV median dose prescription (D50) and robust optimization are viable PTV–free solution (ICRU 91 report) to harmonize the GTV dose was investigated by comparisons with PTV–based SBRT plans.

Methods

Thirteen SBRT plans were optimized for 54 Gy / 3 fractions and prescribed (i) to 95% of the PTV (D95) expanded 5 mm from the ITV on the averaged intensity project (AIP) CT, i.e., PTVITV, (ii) to D95 of PTV derived from the van Herk (VH)‘s margin recipe on the mid–ventilation (MidV)–CT, i.e., PTVVH, (iii) to ITV D98 by worst case scenario (WCS) optimization on AIP,i.e., WCSITV and (iv) to GTV D98 by WCS using all 4DCT images, i.e., WCSGTV. These plans were subsequently recalculated on all 4DCT images and deformably summed on the MidV–CT. The dose differences between these plans were compared for the GTV and selected normal organs by the Friedman tests while the variability was compared by the Levene’s tests. The phase–to–phase changes of GTV dose through the respiration were assessed as an indirect measure of the possible increase of photon fluence owing to the type–B dose engine. Finally, all plans were renormalized to GTV D50 and all the dosimetric analyses were repeated to assess the relative influences of the SBRT planning concept and prescription method on the variability of target dose.

Results

By coverage prescriptions (i) to (iv), significantly smaller chest wall volume receiving ≥30 Gy (CWV30) and normal lung ≥20 Gy (NLV20Gy) were achieved by WCSITV and WCSGTV compared to PTVITV and PTVVH (p > 0.05). These plans differed significantly in the recalculated and summed GTV D2, D50 and D98 (p <  0.05). The inter–patient variability of all GTV dose parameters is however equal between these plans (Levene’s tests; p > 0.05). Renormalizing these plans to GTV D50 reduces their differences in GTV D2, and D98 to insignificant level (p > 0.05) and their inter–patient variability of all GTV dose parameters. None of these plans showed significant differences in GTV D2, D50 and D98 between respiratory phases, nor their inter–phase variability is significant.

Conclusion

Inconsistent GTV dose is not unique to PTV concept but occurs to other PTV–free concept in lung SBRT. GTV D50 renormalization effectively harmonizes the target dose among patients and SBRT concepts of geometric uncertainty management.
Laparoscopic omental flap for the treatment of thoracic aortic graft infection: report of two cases and review of the literature
Authors: Zhou Jiawei , Sun Junfeng , Yao Xingxing , Zhao Guochang , Sun Fuqiang , Sheng Weiyong , Lu Fanfan , Zhan Haibo , Liu Chao
Published: May 2020

Background

Thoracic aortic graft infection (TAGI) is a rare and serious complication after surgery for which the treatment is controversial and challenging. Rather than following the traditional surgical strategy of graft replacement and extensive debridement, we have chosen to preserve the graft and cover it by a laparoscopic omental flap. In this article, we describe the clinical manifestation, diagnostic modalities, and treatment of this disease and analyze the role of laparoscopic omental flaps in its treatment.

Case presentation

We present two cases of thoracic aortic graft infections that had undergone surgical graft replacement for acute Stanford type A dissection. Their clinical manifestation of infection was atypical, with computed tomography suggesting infection of the grafts. Both patients were successfully treated with debridement, laparoscopic omental transposition, and antibiotics. The first case, a 55-year-old male, was found to have an infection at the aortic arch. The second case is a 52-year-old male who was found to have infection at the ascending aorta and arch. Surprisingly, both intraoperative cultures were negative. The infections were brought under control and the patients recovered steadily after surgery. Early follow-up results showed no signs of graft infection.

Conclusion

These findings suggest that graft replacement for the treatment of TAGI is not always necessary in selected patients. Conservative surgical treatment, including laparoscopic omental transposition, is effective and less invasive for treating TAGI.
LIG4 syndrome: clinical and molecular characterization in a Chinese cohort
Authors: Sun Bijun , Chen Qiuyu , Wang Ying , Liu Danru , Hou Jia , Wang Wenjie , Ying Wenjing , Hui Xiaoying , Zhou Qinhua , Sun Jinqiao , Wang Xiaochuan
Published: May 2020

Background

DNA Ligase IV (LIG4) syndrome is a rare disease with few reports to date. Patients suffer from a broad spectrum of clinical features, including microcephaly, growth retardation, developmental delay, dysmorphic facial features, combined immunodeficiency, and malignancy predisposition. There may be a potential association between genotypes and phenotypes. We investigated the characteristics of LIG4 syndrome in a Chinese cohort.

Results

All seven patients had growth restriction. Most patients (6/7) had significant microcephaly (< − 3 SD). Recurrent bacterial infections of the lungs and intestines were the most common symptoms. One patient had myelodysplastic syndromes. One patient presented with an inflammatory bowel disease (IBD)-like phenotype. Patients presented with combined immunodeficiency. The proportions of naïve CD4+ and naïve CD8+ T cells decreased notably in five patients. All patients harbored compound heterozygous mutations in the LIG4 gene, which consisted of a missense mutation (c.833G > T, p.R278L) and a deletion shift mutation, primarily c.1271_1275delAAAGA (p.K424Rfs*20). Two other deletion mutations, c.1144_1145delCT and c.1277_1278delAA, were novel. Patients with p.K424Rfs*20/p.R278 may have milder dysmorphism but more significant IgA/IgM deficiency compared to the frequently reported genotype p.R814X/p.K424Rfs*20. One patient underwent umbilical cord blood stem cell transplantation (UCBSCT) but died.

Conclusions

The present study reported the clinical and molecular characteristics of a Chinese cohort with LIG4 syndrome, and the results further expand the phenotypic and genotypic spectrum and our understanding of genotype-to-phenotype correlations in LIG4 syndrome.
Implementation outcomes of cognitive behavioural therapy delivered by non-specialists for common mental disorders and substance-use disorders in low- and middle-income countries: a systematic review
Authors: Verhey Ibone J. , Ryan Grace K. , Scherer Nathaniel , Magidson Jessica F.
Published: May 2020

Due to severe shortages of specialist mental health personnel in low- and middle-income countries (LMICs), psychological therapies are increasingly being delivered by non-specialist health workers (NSHWs). Previous reviews have investigated the effectiveness of NSHW-delivered psychological therapies, including cognitive behavioural therapy (CBT), in LMIC settings. This systematic review aims to synthesise findings on the implementation outcomes of NSHW-delivered CBT interventions addressing common mental disorders and substance-use disorders in LMICs. Four databases were searched, yielding 3211 records, 18 of which met all inclusion criteria. We extracted and synthesised qualitative and quantitative data across eight implementation outcomes: acceptability, adoption, appropriateness, feasibility, fidelity, implementation cost, penetration and sustainability. Findings suggest that delivery of CBT-based interventions by NSHWs can be acceptable, appropriate and feasible in LMIC settings. However, more research is needed to better evaluate these and other under-reported implementation outcomes.
Differentiation and localization of interneurons in the developing spinal cord depends on DOT1L expression
Authors: Gray de Cristoforis Angelica , Ferrari Francesco , Clotman Frédéric , Vogel Tanja
Published: May 2020

Genetic and epigenetic factors contribute to the development of the spinal cord. Failure in correct exertion of the developmental programs, including neurulation, neural tube closure and neurogenesis of the diverse spinal cord neuronal subtypes results in defects of variable severity. We here report on the histone methyltransferase Disruptor of Telomeric 1 Like (DOT1L), which mediates histone H3 lysine 79 (H3K79) methylation. Conditional inactivation of DOT1L using Wnt1-cre as driver (Dot1l-cKO) showed that DOT1L expression is essential for spinal cord neurogenesis and localization of diverse neuronal subtypes, similar to its function in the development of the cerebral cortex and cerebellum. Transcriptome analysis revealed that DOT1L deficiency favored differentiation over progenitor proliferation. Dot1l-cKO mainly decreased the numbers of dI1 interneurons expressing Lhx2. In contrast, Lhx9 expressing dI1 interneurons did not change in numbers but localized differently upon Dot1l-cKO. Similarly, loss of DOT1L affected localization but not generation of dI2, dI3, dI5, V0 and V1 interneurons. The resulting derailed interneuron patterns might be responsible for increased cell death, occurrence of which was restricted to the late developmental stage E18.5. Together our data indicate that DOT1L is essential for subtype-specific neurogenesis, migration and localization of dorsal and ventral interneurons in the developing spinal cord, in part by regulating transcriptional activation of Lhx2.
Protocol for the process evaluation of a cluster randomised controlled trial to determine the effectiveness and cost-effectiveness of independent pharmacist prescribing in care home: the CHIPPS study
Authors:   On behalf of the CHIPPS Team, Bond Christine M. , Holland Richard , Alldred David P. , Arthur Antony , Barton Garry , Birt Linda , Blyth Annie , Desborough James , Ford Joanna , Handford Christine , Hill Helen , Hughes Carmel M. , Maskrey Vivienne , Massey Kate , Myint Phyo K. , Norris Nigel , Poland Fiona M. , Shepstone Lee , Zermansky Arnold , Wright David
Published: May 2020

Background

Prescribing, monitoring and administration of medicines in care homes could be improved. A cluster randomised controlled trial (RCT) is ongoing to evaluate the effectiveness of an independent prescribing pharmacist assuming responsibility for medicines management in care homes compared to usual care.

Aims and Objectives

To conduct a mixed-methods process evaluation of the RCT, in line with Medical Research Council (MRC) process evaluation guidance, to inform interpretation of main trial findings and if the service is found to be effective and efficient, to inform subsequent implementation.

Objectives

To describe the intervention as delivered in terms of quality, quantity, adaptations and variations across triads and time.

To explore the effects of individual intervention components on the primary outcomes.

To investigate the mechanisms of impact.

To describe the perceived effectiveness of relevant intervention components [including pharmacist independent prescriber (PIP) training and care home staff training] from participant [general practitioner (GP), care home, PIP and resident/relative] perspectives.

To describe the characteristics of GP, care home, PIP and resident participants to assess reach.

To estimate the extent to which intervention delivery is normalised among the intervention healthcare professionals and related practice staff.

Methods

A mix of quantitative (surveys, record reviews) and qualitative (interviews) approaches will be used to collect data on the extent of the delivery of detailed tasks required to implement the new service, to collect data to confirm the mechanism of impact as hypothesised in the logic model, to collect explanatory process and final outcome data, and data on contextual factors which could have facilitated or hindered effective and efficient delivery of the service.

Discussion

Recruitment is ongoing and the trial should complete in early 2020. The systematic and comprehensive approach that is being adopted will ensure data is captured on all aspects of the study, and allow a full understanding of the implementation of the service and the RCT findings. With so many interrelated factors involved it is important that a process evaluation is undertaken to enable us to identify which elements of the service were deemed to be effective, explain any differences seen, and identify enablers, barriers and future adaptions.

Trial registration

ISRCTN17847169.

Date registered: 15 December 2017.
Ancestry-specific predisposing germline variants in cancer
Authors:   TCGA Analysis Network, Oak Ninad , Cherniack Andrew D. , Mashl R. Jay , Hirsch Fred R. , Ding Li , Beroukhim Rameen , Gümüş Zeynep H. , Plon Sharon E. , Huang Kuan-lin
Published: May 2020

Background

Distinct prevalence of inherited genetic predisposition may partially explain the difference of cancer risks across ancestries. Ancestry-specific analyses of germline genomes are required to inform cancer genetic risk and prognosis of diverse populations.

Methods

We conducted analyses using germline and somatic sequencing data generated by The Cancer Genome Atlas. Collapsing pathogenic and likely pathogenic variants to cancer predisposition genes (CPG), we analyzed the association between CPGs and cancer types within ancestral groups. We also identified the predisposition-associated two-hit events and gene expression effects in tumors.

Results

Genetic ancestry analysis classified the cohort of 9899 cancer cases into individuals of primarily European (N = 8184, 82.7%), African (N = 966, 9.8%), East Asian (N = 649, 6.6%), South Asian (N = 48, 0.5%), Native/Latin American (N = 41, 0.4%), and admixed (N = 11, 0.1%) ancestries. In the African ancestry, we discovered a potentially novel association of BRCA2 in lung squamous cell carcinoma (OR = 41.4 [95% CI, 6.1–275.6]; FDR = 0.002) previously identified in Europeans, along with a known association of BRCA2 in ovarian serous cystadenocarcinoma (OR = 8.5 [95% CI, 1.5–47.4]; FDR = 0.045). In the East Asian ancestry, we discovered one previously known association of BRIP1 in stomach adenocarcinoma (OR = 12.8 [95% CI, 1.8–90.8]; FDR = 0.038). Rare variant burden analysis further identified 7 suggestive associations in African ancestry individuals previously described in European ancestry, including SDHB in pheochromocytoma and paraganglioma, ATM in prostate adenocarcinoma, VHL in kidney renal clear cell carcinoma, FH in kidney renal papillary cell carcinoma, and PTEN in uterine corpus endometrial carcinoma. Most predisposing variants were found exclusively in one ancestry in the TCGA and gnomAD datasets. Loss of heterozygosity was identified for 7 out of the 15 African ancestry carriers of predisposing variants. Further, tumors from the SDHB or BRCA2 carriers showed simultaneous allelic-specific expression and low gene expression of their respective affected genes, and FH splice-site variant carriers showed mis-splicing of FH.

Conclusions

While several CPGs are shared across patients, many pathogenic variants are found to be ancestry-specific and trigger somatic effects. Studies using larger cohorts of diverse ancestries are required to pinpoint ancestry-specific genetic predisposition and inform genetic screening strategies.
Season of birth is associated with increased risk of atopic dermatitis in Japanese infants: a retrospective cohort study
Authors: Kuwabara Yu , Nii Ritsue , Tanaka Keiko , Ishii Eiichi , Nagao Mizuho , Fujisawa Takao
Published: May 2020

Background

Several epidemiological studies have examined the possibility of a relationship between season of birth and atopic dermatitis (AD) and food allergy (FA), yet their results are contradictory. We investigated the association between season of birth and risk of AD and FA in Japanese infants.

Methods

Study subjects were 612 newborn infants born at a single obstetric/pediatric clinic without perinatal diseases. Season of birth was classified as spring (March–May), summer (June–August), autumn (September–November) or winter (December–February). AD was diagnosed according to the United Kingdom Working Party’s criteria. FA was defined as present if there was a history of immediate allergic symptoms within 2 h after ingestion of a food. Specific IgE to the corresponding food was also assessed to support the diagnosis. We assessed the association between season of birth and risk of AD and FA using Cox proportional hazard models.

Results

We identified a total of 365 cases of AD occurring during 3659 person-months of follow-up. Compared with summer birth, autumn, winter, and spring birth were significantly positively associated with the risk of AD: adjusted HRs (95% CIs) were 2.67 (1.96–3.63), 1.42 (1.03–1.95), and 1.43 (1.04–1.98), respectively. We identified a total of 23 cases of physician-diagnosed FA occurring during 6815 person-months of follow-up.

Conclusions

Being born in the summer is associated with a lower risk of AD compared to other seasons of birth. The low incidence of FA in our cohort group made it difficult to establish a valid association between FA and season of birth as the statistical power was low.
The functions of long non-coding RNAs in neural stem cell proliferation and differentiation
Authors: Zhao Yanfang , Liu Hongliang , Zhang Qili , Zhang Yuan
Published: May 2020

The capacities for neural stem cells (NSCs) self-renewal with differentiation are need to be precisely regulated for ensuring brain development and homeostasis. Recently, increasing number of studies have highlighted that long non-coding RNAs (lncRNAs) are associated with NSC fate determination during brain development stages. LncRNAs are a class of non-coding RNAs more than 200 nucleotides without protein-coding potential and function as novel critical regulators in multiple biological processes. However, the correlation between lncRNAs and NSC fate decision still need to be explored in-depth. In this review, we will summarize the roles and molecular mechanisms of lncRNAs focusing on NSCs self-renewal, neurogenesis and gliogenesis over the course of neural development, still more, dysregulation of lncRNAs in all stage of neural development have closely relationship with development disorders or glioma. In brief, lncRNAs may be explored as effective modulators in NSCs related neural development and novel biomarkers for diagnosis and prognosis of neurological disorders in the future.
A survey of Monte Carlo methods for parameter estimation
Authors: Luengo David , Martino Luca , Bugallo Mónica , Elvira Víctor , Särkkä Simo
Published: May 2020

Statistical signal processing applications usually require the estimation of some parameters of interest given a set of observed data. These estimates are typically obtained either by solving a multi-variate optimization problem, as in the maximum likelihood (ML) or maximum a posteriori (MAP) estimators, or by performing a multi-dimensional integration, as in the minimum mean squared error (MMSE) estimators. Unfortunately, analytical expressions for these estimators cannot be found in most real-world applications, and the Monte Carlo (MC) methodology is one feasible approach. MC methods proceed by drawing random samples, either from the desired distribution or from a simpler one, and using them to compute consistent estimators. The most important families of MC algorithms are the Markov chain MC (MCMC) and importance sampling (IS). On the one hand, MCMC methods draw samples from a proposal density, building then an ergodic Markov chain whose stationary distribution is the desired distribution by accepting or rejecting those candidate samples as the new state of the chain. On the other hand, IS techniques draw samples from a simple proposal density and then assign them suitable weights that measure their quality in some appropriate way. In this paper, we perform a thorough review of MC methods for the estimation of static parameters in signal processing applications. A historical note on the development of MC schemes is also provided, followed by the basic MC method and a brief description of the rejection sampling (RS) algorithm, as well as three sections describing many of the most relevant MCMC and IS algorithms, and their combined use. Finally, five numerical examples (including the estimation of the parameters of a chaotic system, a localization problem in wireless sensor networks and a spectral analysis application) are provided in order to demonstrate the performance of the described approaches.
Vision-based patient identification recognition based on image content analysis and support vector machine for medical information system
Authors: Lin Guo-Shiang , Chai Sin-Kuo , Li Hsiang-Min , Lin Jen-Yung
Published: May 2020

In this paper, a vision-based patient identification recognition system based on image content analysis and support vector machine is proposed for medical information system, especially in dermatology. This proposed system is composed of three parts: pre-processing, candidate region detection, and digit recognition. To consider the efficiency of the proposed scheme, image normalization is performed. The color information is used to identify camera-captured screen images. In the pre-processing part, the effect of noise in captured screen images is reduced by a bilateral filter. The color and spatial information is used to initially and roughly locate the candidate region. To reduce the skew effect, a skew correction algorithm based on the Hough transform is developed. A template matching algorithm is used to find special symbols for locating the region of interest (ROI). For digit segmentation, digits are segmented in the ROI based on the vertical projection and adaptive thresholding. For the digit recognition, some features are measured from each digit segment and a classifier based on the support vector machine is applied to recognize digits.

The experiment’s results show that the proposed system could effectively not only use color information to distinguish the captured screen images from the skin images but also detect the ROIs. After the digit segmentation, the accuracy rates of digit recognition are 98.4% and 94.2% for the proposed system and the Tesseract Optical Character Recognition (OCR) software, respectively. These results demonstrate that the proposed system outperforms the Tesseract OCR software in terms of the accuracy rate of digit recognition.
Niche switching and leapfrog foraging: movement ecology of sympatric petrels during the early breeding season
Authors: Quillfeldt Petra , Weimerskirch Henri , Delord Karine , Cherel Yves
Published: May 2020

Background

The timing of events in the early part of the breeding season is crucially important for successful reproduction. Long-lived animals that migrate large distances independently of each other meet at the breeding sites to re-establish their pair bonds and coordinate their breeding duties with their partners.

Methods

Using miniature light-geolocation and immersion data together with blood stable isotopes, we studied the early breeding season in Thin-billed prions Pachyptila belcheri, Antarctic prions P. desolata and Blue petrels Halobaena caerulea breeding at Kerguelen Islands in the Indian Ocean. These three species exhibit differences in their winter habitat and timing of migration, moult and breeding. We hypothesised that these differences would influence their behaviour during the early breeding season.

Results

In line with our hypothesis, we found clear differences not only in the timing of colony attendance, but also in the time budgets while at sea and in habitat use. Both early breeding Blue petrels and late breeding Antarctic prions spent about 8 h per day in flight and 15 h foraging. In comparison, Thin-billed prions, which breed in mid-summer, spent less time (5 h daily) in flight and more time (18 h daily) foraging, thus maximizing the time spent foraging during the longest daylight days of the year. While the ecological habitat parameters (sea temperature, wind, productivity) of Thin-billed prions and Blue petrels were relatively stable throughout the year, Antarctic prions showed clear niche switching, caused by leapfrogging between the northernmost winter distribution to the southernmost distribution during the early breeding season. Blood stable isotopes confirmed the habitat switch between the inter-breeding and early breeding periods and highlighted trophic segregation with Blue petrels feeding more on fish and Antarctic petrels more on crustaceans during the early breeding period.

Conclusion

We found that the three sympatric petrel species segregated in time and space, both in the winter and the early breeding season. The interplay of timing and distribution meant that the three species show the full range of migratory strategies, from niche-tracking Blue petrels to niche-switching Antarctic prions. The latitudinal distribution resembled the leapfrogging of terrestrial avian migrant species or populations.
Short-term water demand forecasting using hybrid supervised and unsupervised machine learning model
Authors: Bata Mo’tamad , Carriveau Rupp , Ting David S.-K.
Published: May 2020

Regression Tree (RT) forecasting models are widely used in short-term demand forecasting. Likewise, Self-Organizing Maps (SOM) models are known for their ability to cluster and organize unlabeled big data. Herein, a combination of these two Machine Learning (ML) techniques is proposed and compared to a standalone RT and a Seasonal Autoregressive Integrated Moving Average (SARIMA) models, in forecasting the short-term water demand of a municipality. The inclusion of the Unsupervised Machine Learning clustering model has resulted in a significant improvement in the performance of the Supervised Machine Learning forecasting model. The results show that using the output of the SOM clustering model as an input for the RT forecasting model can, on average, double the accuracy of water demand forecasting. The Mean Absolute Percentage Error (MAPE) and the Normalized Root Mean Squared Error (NRMSE) were calculated for the proposed models forecasting 1 h, 8 h, 24 h, and 7 days ahead. The results show that the hybrid models outperformed the standalone RT model, and the broadly used SARIMA model. On average, hybrid models achieved double accuracy in all 4 forecast periodicities. The increase in forecasting accuracy afforded by this hybridized modeling approach is encouraging. In our application, it shows promises for more efficient energy and water management at the water utilities.
Evaluating Fidelity of reporting in randomized controlled trials on childhood acute lymphocytic leukemia
Authors: Jellison Samuel , Hoffsommer Nicholas , Hoelscher Alexander , Vassar Matt
Published: May 2020

Background

Randomized controlled trials (RCTs) play an integral role in childhood cancer research. Several efforts to improve the quality of reporting of clinical trials have been published in recent years, including the TIDieR checklist. Many reviews have since used TIDieR to evaluate how well RCTs are being reported, but no such study has yet been done in childhood cancer. The aim of this study is to evaluate adherence of RCTs involving acute lymphocytic leukemia (ALL) to the TIDieR checklist.

Methods

The PubMed database was used to screen for RCTs involving ALL published since 2015. Of 1546 articles identified, 46 met study criteria and were then evaluated against the TIDieR 12-point checklist to measure the degree of adherence.

Results

Of the 46 articles included, 9 (19.6%) met full TIDieR criteria. Seven of the 9 reported non-pharmacological interventions, and the remaining 2 reported pharmacological interventions. The average article properly reported 8.98/12 checklist items. Item 5 (intervention provider) was the most poorly reported item, properly reported in only 34.8% of articles.

Conclusion

We conclude that overall TIDieR adherence is low and needs to be adhered to more fully in order to improve research in ALL as well as in all childhood cancers.