bluuebunny/crossref_metadata_2025_split huggingface dataset:
Study protocol: improving cognition in people with progressive multiple sclerosis: a multi-arm, randomized, blinded, sham-controlled trial of cognitive rehabilitation and aerobic exercise (COGEx)
Authors:   On behalf of the CogEx Research Team, Feinstein Anthony , Amato Maria Pia , Brichetto Giampaolo , Chataway Jeremy , Chiaravalloti Nancy , Dalgas Ulrik , DeLuca John , Feys Peter , Filippi Massimo , Freeman Jennifer , Meza Cecilia , Inglese Matilde , Motl Robert W. , Rocca Maria Assunta , Sandroff Brian M. , Salter Amber , Cutter Gary 
Published: May 2020

Abstract
Background
Cognitive dysfunction affects up to 70% of people with progressive MS (PMS). It can exert a deleterious effect on activities of daily living, employment and relationships. Preliminary evidence suggests that performance can improve with cognitive rehabilitation (CR) and aerobic exercise (EX), but existing data are predominantly from people with relapsing-remitting MS without cognitive impairment. There is therefore a need to investigate whether this is also the case in people with progressive forms of the disease who have objectively identified cognitive impairment. It is hypothesized that CR and EX are effective treatments for people with PMS who have cognitive impairment, in particular processing speed (PS) deficits, and that a combination of these two treatments is more effective than each individual treatment given alone. We further hypothesize that improvements in PS will be associated with modifications of functional and/or structural plasticity within specific brain networks/regions involved in PS measured with advanced MRI techniques.

Methods
This study is a multisite, randomized, double-blinded, sham controlled clinical trial of CR and aerobic exercise. Three hundred and sixty subjects from 11 sites will be randomly assigned into one of four groups: CR plus aerobic exercise; CR plus sham exercise; CR sham plus aerobic exercise and CR sham plus sham exercise. Subjects will participate in the assigned treatments for 12 weeks, twice a week.
All subjects will have a cognitive and physical assessment at baseline, 12 weeks and 24 weeks. In an embedded sub-study, approximately 30% of subjects will undergo structural and functional MRI to investigate the neural mechanisms underlying the behavioral response. The primary outcome is the Symbol Digit Modalities Test (SDMT) measuring PS. Secondary outcome measures include: indices of verbal and non-verbal memory, depression, walking speed and a dual cognitive-motor task and MRI.

Discussion
The study is being undertaken in 6 countries (11 centres) in multiple languages (English, Italian, Danish, Dutch); with testing material validated and standardized in these languages. The rationale for this approach is to obtain a robustly powered sample size and to demonstrate that these two interventions can be given effectively in multiple countries and in different languages.

Trial registration
The trial was registered on September 20th 2018 at www.clinicaltrials.gov having identifier NCT03679468. Registration was performed before recruitment was initiated.
The evaluation of the distance between the popliteus tendon and the lateral collateral ligament footprint and the implant in Total knee Arthroplasty using a 3-dimensional template
Authors: Takubo Akihito , Ryu Keinosuke , Iriuchishima Takanori , Nagaoka Masahiro , Tokuhashi Yasuaki , Aizawa Shin 
Published: May 2020

Abstract
Background
The popliteus tendon (PT) or lateral collateral ligament (LCL) stabilizes the postero-lateral aspects of the knees. When surgeons perform total knee arthroplasty (TKA), PT and LCL iatrogenic injuries are a risk because the femoral attachments are relatively close to the femoral bone resection area. The purpose of this study was to evaluate the distance between the PT or LCL footprint and the TKA implant using a 3D template system and to evaluate any significant differences according to the implant model.

Methods
Eighteen non-paired formalin fixed cadaveric lower limbs were used (average age: 80.3). Whole length lower limbs were resected from the pelvis. All the surrounding soft tissue except the PT, knee ligaments and meniscus were removed from the limb. Careful dissection of the PT and LCL was performed, and the femoral footprints were detected. Each footprint periphery was marked with a 1.5 mm K-wire. Computed tomography (CT) scanning of the whole lower limb was then performed. The CT data was analyzed with a 3D template system. This simulation models for TKA were the Journey II BCS and the Persona PS. The area of each footprint, and the length between the most distal and posterior point of the lateral femoral condyle and the edge of each footprint were measured. Matching the implant model to the CT image of the femur, the shortest length between each footprint and the bone resection area were calculated.

Results
PT and LCL footprint were detected in all knees. The area of the PT and LCL footprints was 38.7 ± 17.7 mm2 and 58.0 ± 24.6 mm2, respectively. The length between the most distal and posterior point of the lateral femoral condyle and the edge of the PT footprint was 10.3 ± 2.4 mm and 14.2 ± 2.8 mm, respectively. The length between most distal and most posterior point of the lateral femoral condyle and the edge of the LCL footprint was 16.3 ± 2.3 mm and 15.5 ± 3.3 mm, respectively. Under TKA simulation, the shortest length between the PT footprint and the femoral bone resection area for the Journey II BCS and the Persona PS was 4.3 ± 2.5 mm and 3.2 ± 2.9 mm, respectively. The shortest length between the LCL footprint and the femoral bone resection area for the Journey II BCS and the Persona PS was 7.2 ± 2.3 mm and 5.6 ± 2.1 mm, respectively. The PT attachment was damaged by the bone resection of the Journey II BCS and the Persona PS TKA in 3 and 9 knees, respectively.

Conclusion
The PT and LCL femoral attachments existed close to the femoral bone resection area of the TKA. To prevent postero-lateral instability in TKA, careful attention is needed to avoid damage to the PT and LCL during surgical procedures.
Implementing volunteer-navigation for older persons with advanced chronic illness (Nav-CARE): a knowledge to action study
Authors: Pesut Barbara , Duggleby Wendy , Warner Grace , Kervin Emily , Bruce Paxton , Antifeau Elisabeth , Hooper Brenda 
Published: May 2020

Abstract
Background
Nav-CARE is a volunteer-led intervention designed to build upon strategic directions in palliative care: a palliative approach to care, a public health/compassionate community approach to care, and enhancing the capacity of volunteerism. Nav-CARE uses specially trained volunteers to provide lay navigation for older persons and family living at home with advanced chronic illness. The goal of this study was to better understand the implementation factors that influenced the utilization of Nav-CARE in eight diverse Canadian contexts.

Methods
This was a Knowledge to Action study using the planned action cycle for Nav-CARE developed through previous studies. Participants were eight community-based hospice societies located in diverse geographic contexts and with diverse capacities. Implementation data was collected at baseline, midpoint, and endpoint using qualitative individual and group interviews. Field notes of all interactions with study sites were also used as part of the data set. Data was analyzed using qualitative descriptive techniques. The study received ethical approval from three university behavioural review boards. All participants provided written consent.

Results
At baseline, stakeholders perceived Nav-CARE to be a good fit with the strategic directions of their organization by providing early palliative support, by facilitating outreach into the community and by changing the public perception of palliative care. The contextual factors that determined the ease with which Nav-CARE was implemented included the volunteer coordinator champion, organizational capacity and connection, the ability to successfully recruit older persons, and the adequacy of volunteer preparation and mentorship.

Conclusions
This study highlighted the importance of community-based champions for the success of volunteer-led initiatives and the critical need for support and mentorship for both volunteers and those who lead them. Further, although the underutilization of hospice has been widely recognized, it is vital to recognize the limitations of their capacity. New initiatives such as Nav-CARE, which are designed to enhance their contributions to palliative care, need to be accompanied by adequate resources. Finally, this study illustrated the need to think carefully about the language and role of hospice societies as palliative care moves toward a public health approach to care.
The endothelium, a key actor in organ development and hPSC-derived organoid vascularization
Authors: Vargas-Valderrama Alejandra , Messina Antonietta , Mitjavila-Garcia Maria Teresa , Guenou Hind 
Published: May 2020

AbstractOver the last 4 decades, cell culture techniques have evolved towards the creation of in vitro multicellular entities that incorporate the three-dimensional complexity of in vivo tissues and organs. As a result, stem cells and adult progenitor cells have been used to derive self-organized 3D cell aggregates that mimic the morphological and functional traits of organs in vitro. These so-called organoids were first generated from primary animal and human tissues, then human pluripotent stem cells (hPSCs) arose as a new tool for organoid generation. Due to their self-renewal capacity and differentiation potential, hPSCs are an unlimited source of cells used for organoids. Today, hPSC-derived small intestinal, kidney, brain, liver, and pancreas organoids, among others, have been produced and are promising in vitro human models for diverse applications, including fundamental research, drug development and regenerative medicine. However, achieving in vivo-like organ complexity and maturation in vitro remains a challenge. Current hPSC-derived organoids are often limited in size and developmental state, resembling embryonic or fetal organs rather than adult organs. The use of endothelial cells to vascularize hPSC-derived organoids may represent a key to ensuring oxygen and nutrient distribution in large organoids, thus contributing to the maturation of adult-like organoids through paracrine signaling.Here, we review the current state of the art regarding vascularized hPSC-derived organoids (vhPSC-Orgs). We analyze the progress achieved in the generation of organoids derived from the three primary germ layers (endoderm, mesoderm and ectoderm) exemplified by the pancreas, liver, kidneys and brain. Special attention will be given to the role of the endothelium in the organogenesis of the aforementioned organs, the sources of endothelial cells employed in vhPSC-Org protocols and the remaining challenges preventing the creation of ex vivo functional and vascularized organs.
Long noncoding RNA ZFAS1 promoting small nucleolar RNA-mediated 2′-O-methylation via NOP58 recruitment in colorectal cancer
Authors: Wu Huizhe , Qin Wenyan , Lu Senxu , Wang Xiufang , Zhang Jing , Sun Tong , Hu Xiaoyun , Li Yalun , Chen Qiuchen , Wang Yuanhe , Zhao Haishan , Piao Haiyan , Zhang Rui , Wei Minjie 
Published: May 2020

Abstract
Background
Increasing evidence supports the role of small nucleolar RNAs (snoRNAs) and long non-coding RNAs (lncRNAs) as master gene regulators at the epigenetic modification level. However, the underlying mechanism of these functional ncRNAs in colorectal cancer (CRC) has not been well investigated.

Methods
The dysregulated expression profiling of lncRNAs-snoRNAs-mRNAs and their correlations and co-expression enrichment were assessed by GeneChip microarray analysis. The candidate lncRNAs, snoRNAs, and target genes were detected by in situ hybridization (ISH), RT-PCR, qPCR and immunofluorescence (IF) assays. The biological functions of these factors were investigated using in vitro and in vivo studies that included CCK8, trans-well, cell apoptosis, IF assay, western blot method, and the xenograft mice models. rRNA 2′-O-methylation (Me) activities were determined by the RTL-P assay and a novel double-stranded primer based on the single-stranded toehold (DPBST) assay. The underlying molecular mechanisms were explored by bioinformatics and RNA stability, RNA fluorescence ISH, RNA pull-down and translation inhibition assays.

Results
To demonstrate the involvement of lncRNA and snoRNAs in 2′-O-Me modification during tumorigenesis, we uncovered a previously unreported mechanism linking the snoRNPs NOP58 regulated by ZFAS1 in control of SNORD12C, SNORD78 mediated rRNA 2′-O-Me activities in CRC initiation and development. Specifically, ZFAS1 exerts its oncogenic functions and significantly up-regulated accompanied by elevated NOP58, SNORD12C/78 expression in CRC cells and tissues. ZFAS1 knockdown suppressed CRC cell proliferation, migration, and increased cell apoptosis, and this inhibitory effect could be reversed by NOP58 overexpression in vitro and in vivo. Mechanistically, the NOP58 protein could be recognized by the specific motif (AAGA or CAGA) of ZFAS1. This event accelerates the assembly of SNORD12C/78 to allow for further guiding of 2′-O-Me at the corresponding Gm3878 and Gm4593 sites. Importantly, silencing SNORD12C or 78 reduced the rRNAs 2′-O-Me activities, which could be rescued by overexpression ZFAS1, and this subsequently inhibits the RNA stability and translation activity of their downstream targets (e.g., EIF4A3 and LAMC2).

Conclusion
The novel ZFAS1-NOP58-SNORD12C/78-EIF4A3/LAMC2 signaling axis that functions in CRC tumorigenesis provides a better understanding regarding the role of lncRNA-snoRNP-mediated rRNAs 2′-O-Me activities for the prevention and treatment of CRC.
Value migration: digitalization of shipping as a mechanism of industry dethronement
Authors: Poulis Konstantinos , Galanakis Gregorios C. , Triantafillou Gregory T. , Poulis Efthimios 
Published: May 2020

AbstractIn this conceptual paper, we review latest developments related to unmanned vessels and sketch potential scenarios that implicate with the existing maritime industry structure. On the one hand, we isolate a range of challenges that make the imminent realization of unmanned vessels seem like a rather utopian pursuit. On the other hand, we explain the reasons that may catalyse their emergence. Inspired by these opposing tensions, we highlight that the digital transformation of the shipping industry has the potential to enhance value within the industry’s ecosystem. However, we also contend that unmanned vessels -if realized- pose a very particular threat to the identity of the shipping industry as we know it. In particular, we build upon the concept of value migration and we highlight the drastic existential changes that may likely stem from a shift to non-seafarer-centric shipping. We conclude with questions that matter for industry dethronement purposes i.e., the possibility that existing industry structures may be substantially reconfigured following a removal of the seafarer as the nucleus of value creation in shipping.
Prediction and assessment of demand response potential with coupon incentives in highly renewable power systems
Authors: Ming Hao , Xia Bainan , Lee Ki-Yeob , Adepoju Adekunle , Shakkottai Srinivas , Xie Le 
Published: May 2020

AbstractDemand Response (DR) provides both operational and financial benefits to a variety of stakeholders in the power system. For example, in the deregulated market operated by the Electric Reliability Council of Texas (ERCOT), load serving entities (LSEs) usually purchase electricity from the wholesale market (either in day-ahead or real-time market) and sign fixed retail price contracts with their end-consumers. Therefore, incentivizing end-consumers’ load shift from peak to off-peak hours could benefit the LSE in terms of reducing its purchase of electricity under high prices from the real-time market. As the first-of-its-kind implementation of Coupon Incentive-based Demand Response (CIDR), the EnergyCoupon project provides end-consumers with dynamic time-of-use DR event announcements, individualized load reduction targets with EnergyCoupons as the incentive for meeting these targets, as well as periodic lotteries using these coupons as lottery tickets for winning dollar-value gifts. A number of methodologies are developed for this special type of DR program including price/baseline prediction, individualized target setting and a lottery mechanism. This paper summarizes the methodologies, design, critical findings, as well as the potential generalization of such an experiment. Comparison of the EnergyCoupon with a conventional Time-of-Use (TOU) price-based DR program is also conducted. Experimental results in the year 2017 show that by combining dynamic coupon offers with periodic lotteries, the effective cost for demand response providers in EnergyCoupon can be substantially reduced, while achieving a similar level of demand reduction as conventional DR programs.
Obesity, Polycystic Ovary Syndrome, and Infertility: A New Avenue for GLP-1 Receptor Agonists
Authors: Cena Hellas , Chiovato Luca , Nappi Rossella E 
Published: May 2020

Abstract

Context
Obesity is responsible for an increased risk of sub-fecundity and infertility. Obese women show poorer reproductive outcomes regardless of the mode of conception, and higher body mass index (BMI) is associated with poorer fertility prognosis. Polycystic ovary syndrome (PCOS) is one of the leading causes of infertility, and many women with PCOS are also overweight or obese.

Evidence Acquisition
The aim of the present narrative review is to describe the mechanisms responsible for the development of infertility and PCOS in women with obesity/overweight, with a focus on the emerging role of glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1 RAs) as a therapeutic option for obese women with PCOS.

Evidence synthesis
Weight reduction represents the most significant factor affecting fertility and pregnancy outcomes. Current experimental and clinical evidence suggests the presence of an underlying pathophysiological link between obesity, GLP-1 kinetic alterations, and PCOS pathogenesis. Based on the positive results in patients affected by obesity, with or without diabetes, the administration of GLP-1 RA (mainly liraglutide) alone or in combination with metformin has been investigated in women with obesity and PCOS. Several studies demonstrated significant weight loss and testosterone reduction, with mixed results relative to improvements in insulin resistance parameters and menstrual patterns.

Conclusions
The weight loss effects of GLP-1 RA offer a unique opportunity to expand the treatment options available to PCOS patients.
Loss of CPAP in developing mouse brain and its functional implication for human primary microcephaly
Authors: Lin Yi-Nan , Lee Ying-Shan , Li Shu-Kuei , Tang Tang K. 
Published: May 2020

ABSTRACT
Primary microcephaly (MCPH) is a neurodevelopmental disorder characterized by small brain size with mental retardation. CPAP (also known as CENPJ), a known microcephaly-associated gene, plays a key role in centriole biogenesis. Here, we generated a previously unreported conditional knockout allele in the mouse Cpap gene. Our results showed that conditional Cpap deletion in the central nervous system preferentially induces formation of monopolar spindles in radial glia progenitors (RGPs) at around embryonic day 14.5 and causes robust apoptosis that severely disrupts embryonic brains. Interestingly, microcephalic brains with reduced apoptosis are detected in conditional Cpap gene-deleted mice that lose only one allele of p53 (also known as Trp53), while simultaneous removal of p53 and Cpap rescues RGP death. Furthermore, Cpap deletion leads to cilia loss, RGP mislocalization, junctional integrity disruption, massive heterotopia and severe cerebellar hypoplasia. Together, these findings indicate that complete CPAP loss leads to severe and complex phenotypes in developing mouse brain, and provide new insights into the causes of MCPH.
Crumbs, Galla and Xpd are required for Kinesin-5 regulation in mitosis and organ growth in Drosophila
Authors: Hwang Ji-Hyun , Vuong Linh Thuong , Choi Kwang-Wook 
Published: May 2020

ABSTRACT
Xeroderma Pigmentosum D (XPD, also known as ERCC2) is a multi-functional protein involved in transcription, DNA repair and chromosome segregation. In Drosophila, Xpd interacts with Crumbs (Crb) and Galla to regulate mitosis during embryogenesis. It is unknown how these proteins are linked to mitosis. Here, we show that Crb, Galla-2 and Xpd regulate nuclear division in the syncytial embryo by interacting with Klp61F, the Drosophila mitotic Kinesin-5 associated with bipolar spindles. Crb, Galla-2 and Xpd physically interact with Klp61F and colocalize to mitotic spindles. Knockdown of any of these proteins results in similar mitotic defects. These phenotypes are restored by overexpression of Klp61F, suggesting that Klp61F is a major effector. Mitotic defects of galla-2 RNAi are suppressed by Xpd overexpression but not vice versa. Depletion of Crb, Galla-2 or Xpd results in a reduction of Klp61F levels. Reducing proteasome function restores Klp61F levels and suppresses mitotic defects caused by knockdown of Crb, Galla-2 or Xpd. Furthermore, eye growth is regulated by Xpd and Klp61F. Hence, we propose that Crb, Galla-2 and Xpd interact to maintain the level of Klp61F during mitosis and organ growth.
Effectiveness of interventions to reduce adverse outcomes among older adults following emergency department discharge: Protocol for an overview of systematic reviews
Authors: Conneely Mairéad , Robinson Katie , Leahy Siobhán , Trépel Dominic , Jordan Fionnuala , Galvin Rose 
Published: May 2020

Background: Older adults are frequent users of Emergency departments (ED) and this trend will continue due to population ageing and the associated increase in healthcare needs. Older adults are vulnerable to adverse outcomes following ED discharge. A number of heterogeneous interventions have been developed and implemented to improve clinical outcomes among this cohort. A growing number of systematic reviews have synthesised evidence regarding ED interventions using varying methodologies. This overview aims to synthesise the totality of evidence in order to evaluate the effectiveness of interventions to reduce adverse outcomes in older adults discharged from the ED. Methods: To identify relevant reviews, the following databases will be searched: Cochrane Database of Systematic reviews, Joanna Briggs Institute Database of Systematic Reviews and Implementation Reports, Databases of Abstracts of Reviews of Effects, PubMed, MEDLINE, Epistemonikos, Ageline, Embase, PEDro, Scopus, CINAHL and the PROSPERO register. The search for grey literature will include Open Grey and Grey Literature Reports. Systematic reviews of randomised controlled trials will be analysed to assess the effect of ED interventions on clinical and process outcomes in older adults. Methodological quality of the reviews will be assessed using the Assessment of Multiple Systematic Reviews 2 tool. The review will be reported in accordance to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Summary of findings will include a hierarchical rank of interventions based on estimates of effects and the quality of evidence. Discussion: This overview is required given the number of systematic reviews published regarding the effectiveness of various ED interventions for older adults at risk of adverse outcomes following discharge from the ED. There is a need to examine the totality of evidence using rigorous analytic techniques to inform best care and potentially develop a hierarchy of treatment options. PROSPERO registration: CRD42020145315 (28/04/2020)