bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intra-fraction displacement of the prostate bed during post-prostatectomy radiotherapy
Authors: Bell Linda J. , Eade Thomas , Hruby George , Bromley Regina , Kneebone Andrew 
Published: January 2021

Abstract
Background
To measure intra-fraction displacement (IFD) in post-prostatectomy patients treated with anisotropic margins and daily soft tissue matching.

Methods
Pre-treatment cone beam computed tomography (CBCT) scans were acquired daily and post-treatment CBCTs for the first week then weekly on 46 patients. The displacement between the scans was calculated retrospectively to measure IFD of the prostate bed (PB). The marginal miss (MM) rate, and the effect of time between imaging was assessed.

Results
A total of 392 post-treatment CBCT’s were reviewed from 46 patients. The absolute mean (95% CI) IFD was 1.5 mm (1.3–1.7 mm) in the AP direction, 1.0 mm (0.9–1.2 mm) SI, 0.8 mm (0.7–0.9 mm) LR, and 2.4 mm (2.2–2.5 mm) 3D displacement. IFD ≥  ± 3 mm and ≥  ± 5 mm was 24.7% and 5.4% respectively. MM of the PB was detected in 33 of 392 post-treatment CBCT (8.4%) and lymph nodes in 6 of 211 post-treatment CBCT images (2.8%). Causes of MM due to IFD included changes in the bladder (87.9%), rectum (66.7%) and buttock muscles (6%). A time ≥ 9 min between the pre and post-treatment CBCT demonstrated that movement ≥ 3 mm and 5 mm increased from 19.2 to 40.5% and 5 to 8.1% respectively.

Conclusions
IFD during PB irradiation was typically small, but was a major contributor to an 8.4% MM rate when using daily soft tissue match and tight anisotropic margins.
Outcome and experience of arthroscopic lateral retinacular release combined with lateral patelloplasty in the management of excessive lateral pressure syndrome
Authors: Wang Cheng-Liang , Chen Ji-Bin , Li Te 
Published: January 2021

AbstractBackgroundOnly a few studies have described the effect of full arthroscopic surgery in treatment of excessive lateral pressure syndrome (ELPS). Therefore, the purpose of this study was to assess the clinical efficacy and experience of total arthroscopic lateral retinacular (LR) release and lateral patelloplasty for the treatment of ELPS.MethodsA total of 73 patients (88 knees) with ELPS underwent arthroscopic LR release and lateral patelloplasty. The visual analogue scale (VAS), Kujala score, Lysholm scores, patella medial pushing distance, patellar tilt angle (PTA), and lateral patellofemoral angle (LPFA) were measured and evaluated before and after surgery.ResultsFollow-up ranged from 12 to 36 months with an average of 24 ± 5.8 months. The VAS was significantly lower at the last follow-up than before surgery (P< 0.01). The patella medial pushing distance, Kujala score, Lysholm score, PTA, and LPFA were significantly higher at the last follow-up than before surgery (P< 0.01, respectively). Years and lateral patella Outerbridge classification at the last follow-up have negative correlation with Kujala score, Lysholm score, Patella medial pushing distance, PTA, and LPFA (P< 0.01, respectively) and have positive correlation with VAS (P< 0.01, respectively). Related complications were not reported.ConclusionsFull arthroscopic LR release combined with lateral patelloplasty in the treatment of ELPS is an effective minimally invasive method, which can effectively correct anomalies of force line and skeleton of patella, relieve pain, and restore knee joint motor function with less complications.
Supportive care needs of patients with rare chronic diseases: multi-method, cross-sectional study
Authors: Depping Miram K. , Uhlenbusch Natalie , von Kodolitsch Yskert , Klose Hans F. E. , Mautner Victor-Felix , Löwe Bernd 
Published: January 2021

AbstractBackgroundIn the absence of a cure for the majority of rare diseases, the disease management aims to provide optimal supportive care. The goal of this study was to assess supportive care needs in patients with chronic rare diseases.MethodsCross-sectional mixed-method study was conducted using validated self-report scales and open-ended questions to assess supportive care needs. Participants affected by rare diseases across Germany were contacted via patient organizations and centers for rare diseases. N = 304 participants with 81 different rare diseases completed the study, 81.6% were female, mean age was 44.2 years (SD = 12.8, range 16–74). The quantitative results regarding supportive care needs were compared to a reference population of patients affected by cancer (N = 888). Main outcomes were unmet supportive care needs of patients with rare diseases, as assessed by the Supportive Care Needs Survey (SNCS-SF34) and an open-ended question on support wishes.ResultsPatients with rare diseases did not feel sufficiently supported with regard to psychological support, health system and information, physical and daily living, patient care and support, and sexuality needs. The unmet supportive care needs were significantly higher in the patient sample with rare diseases compared to the SCNS-SF34 reference sample of patients with cancer. 60% of patients with rare diseases did not feel sufficiently socially supported.ConclusionsPatients affected by rare diseases have high unmet support needs in all areas studied. Multidisciplinary care, including psychological support and the provision of information regarding the healthcare system, treatment options, disease course and sexuality, might help address these needs.
Musculo-skeletal phenotype of Costello syndrome and cardio-facio-cutaneous syndrome: insights on the functional assessment status
Authors: Leoni Chiara , Romeo Domenico Marco , Pelliccioni Michele , Di Già Mariangela , Onesimo Roberta , Giorgio Valentina , Flex Elisabetta , Tedesco Marta , Tartaglia Marco , Rigante Donato , Valassina Antonio , Zampino Giuseppe 
Published: January 2021

Abstract
Background
Costello syndrome (CS)
and cardio-facio-cutaneous syndrome (CFCS) belong to the RASopathies, a group of neurodevelopmental disorders with skeletal anomalies. Due to their rarity, the characterization of the musculo-skeletal phenotype in both disorders has been poorly characterized.

Patients and methods
Herein we reported data on orthopedic findings and functional status of a large sample of CS and CFCS patients. Thirty-four patients (CS = 17 and CFCS = 17) were recruited. Functional and disability evaluations were performed by assessing the 6-min walking test (6MWT) and Pediatric Outcomes Data Collection Instrument (PODCI). Genotype/phenotype correlation was also provided.

Results
Orthopedic manifestations are highly prevalent in CS and CFCS and overlap in the two disorders. Overall, patients with CS harboring the recurrent HRAS Gly12Ser substitution show a more severe skeletal phenotype compared to patients carrying the Gly12Ala and Gly13Cys variants. Among CFCS patients, those with the MAP2K1/2 variant show different skeletal characteristics compared to BRAF variants, with a higher prevalence of orthopedic abnormalities. Functional assessment showed that patients with CS and CFCS reached lower values compared to the general population, with CFCS patients displaying the lowest scores.

Conclusions
Orthopedic manifestations appear universal features of CS and CFCS and they can evolve across patients’ life. Longitudinal assessment of disability status by using 6MWT and PODCI could be useful to evaluate the functional impact of orthopedic manifestations on patients’ outcome and help planning a tailored treatment of these comorbidities.
One test for all: whole exome sequencing significantly improves the diagnostic yield in growth retarded patients referred for molecular testing for Silver–Russell syndrome
Authors: Meyer Robert , Begemann Matthias , Hübner Christian Thomas , Dey Daniela , Kuechler Alma , Elgizouli Magdeldin , Schara Ulrike , Ambrozaityte Laima , Burnyte Birute , Schröder Carmen , Kenawy Asmaa , Kroisel Peter , Demuth Stephanie , Fekete Gyorgy , Opladen Thomas , Elbracht Miriam , Eggermann Thomas 
Published: January 2021

Abstract
Background
Silver-Russell syndrome (SRS) is an imprinting disorder which is characterised by severe primordial growth retardation, relative macrocephaly and a typical facial gestalt. The clinical heterogeneity of SRS is reflected by a broad spectrum of molecular changes with hypomethylation in 11p15 and maternal uniparental disomy of chromosome 7 (upd(7)mat) as the most frequent findings. Monogenetic causes are rare, but a clinical overlap with numerous other disorders has been reported. However, a comprehensive overview on the contribution of mutations in differential diagnostic genes to phenotypes reminiscent to SRS is missing due to the lack of appropriate tests. With the implementation of next generation sequencing (NGS) tools this limitation can now be circumvented.

Main body
We analysed 75 patients referred for molecular testing for SRS by a NGS-based multigene panel, whole exome sequencing (WES), and trio-based WES. In 21/75 patients a disease-causing variant could be identified among them variants in known SRS genes (IGF2, PLAG1, HMGA2). Several patients carried variants in genes which have not yet been considered as differential diagnoses of SRS.

Conclusions
WES approaches significantly increase the diagnostic yield in patients referred for SRS testing. Several of the identified monogenetic disorders have a major impact on clinical management and genetic counseling.
Long-read transcriptome sequencing reveals abundant promoter diversity in distinct molecular subtypes of gastric cancer
Authors: Huang Kie Kyon , Huang Jiawen , Wu Jeanie Kar Leng , Lee Minghui , Tay Su Ting , Kumar Vikrant , Ramnarayanan Kalpana , Padmanabhan Nisha , Xu Chang , Tan Angie Lay Keng , Chan Charlene , Kappei Dennis , Göke Jonathan , Tan Patrick 
Published: January 2021

AbstractBackgroundDeregulated gene expression is a hallmark of cancer; however, most studies to date have analyzed short-read RNA sequencing data with inherent limitations. Here, we combine PacBio long-read isoform sequencing (Iso-Seq) and Illumina paired-end short-read RNA sequencing to comprehensively survey the transcriptome of gastric cancer (GC), a leading cause of global cancer mortality.ResultsWe performed full-length transcriptome analysis across 10 GC cell lines covering four major GC molecular subtypes (chromosomal unstable, Epstein-Barr positive, genome stable and microsatellite unstable). We identify 60,239 non-redundant full-length transcripts, of which > 66% are novel compared to current transcriptome databases. Novel isoforms are more likely to be cell line and subtype specific, expressed at lower levels with larger number of exons, with longer isoform/coding sequence lengths. Most novel isoforms utilize an alternate first exon, and compared to other alternative splicing categories, are expressed at higher levels and exhibit higher variability. Collectively, we observe alternate promoter usage in 25% of detected genes, with the majority (84.2%) of known/novel promoter pairs exhibiting potential changes in their coding sequences. Mapping these alternate promoters to TCGA GC samples, we identify several cancer-associated isoforms, including novel variants of oncogenes. Tumor-specific transcript isoforms tend to alter protein coding sequences to a larger extent than other isoforms. Analysis of outcome data suggests that novel isoforms may impart additional prognostic information.ConclusionsOur results provide a rich resource of full-length transcriptome data for deeper studies of GC and other gastrointestinal malignancies.
Interleukin (IL)-33 is dispensable for Schistosoma mansoni worm maturation and the maintenance of egg-induced pathology in intestines of infected mice
Authors: Mukendi Jean Pierre Kambala , Nakamura Risa , Uematsu Satoshi , Hamano Shinjiro 
Published: January 2021

Abstract
Background
Schistosomes are trematode worms that dwell in their definitive host’s blood vessels, where females lay eggs that need to be discharged into the environment with host excreta to maintain their life-cycle. Both worms and eggs require type 2 immunity for their maturation and excretion, respectively. However, the immune molecules that orchestrate such immunity remain unclear. Interleukin (IL)-33 is one of the epithelium-derived cytokines that induce type 2 immunity in tissues. The aim of this study was to determine the role of IL-33 in the maturation, reproduction and excretion of Schistosoma mansoni eggs, and in the maintenance of egg-induced pathology in the intestines of mice.

Methods
The morphology of S. mansoni worms and the number of eggs in intestinal tissues were studied at different time points post-infection in S. mansoni-infected IL-33-deficient (IL-33−/−) and wild-type (WT) mice. IL-5 and IL-13 production in the spleens and mesenteric lymph nodes were measured. Tissue histology was performed on the terminal ilea of both infected and non-infected mice.

Results
Worms from IL-33−/− and WT mice did not differ morphologically at 4 and 6 weeks post-infection (wpi). The number of eggs in intestinal tissues of IL-33−/− and WT mice differed only slightly. At 6 wpi, IL-33−/− mice presented impaired type 2 immunity in the intestines, characterized by a decreased production of IL-5 and IL-13 in mesenteric lymph nodes and fewer inflammatory infiltrates with fewer eosinophils in the ilea. There was no difference between IL-33−/− and WT mice in the levels of IL-25 and thymic stromal lymphopoietin (TSLP) in intestinal tissues.

Conclusions
Despite its ability to initiate type 2 immunity in tissues, IL-33 alone seems dispensable for S. mansoni maturation and its absence may not affect much the accumulation of eggs in intestinal tissues. The transient impairment of type 2 immunity observed in the intestines, but not spleens, highlights the importance of IL-33 over IL-25 and TSLP in initiating, but not maintaining, locally-induced type 2 immunity in intestinal tissues during schistosome infection. Further studies are needed to decipher the role of each of these molecules in schistosomiasis and clarify the possible interactions that might exist between them.

Graphical Abstract
The common European mosquitoes Culex pipiens and Aedes albopictus are unable to transmit SARS-CoV-2 after a natural-mimicking challenge with infected blood
Authors: Fortuna Claudia , Montarsi Fabrizio , Severini Francesco , Marsili Giulia , Toma Luciano , Amendola Antonello , Bertola Michela , Michelutti Alice , Ravagnan Silvia , Capelli Gioia , Rezza Giovanni , Di Luca Marco ,   the Working Group
Published: January 2021

AbstractBackgroundOn 11 March 2020, the World Health Organisation (WHO) declared the coronavirus disease 2019 (COVID-19) outbreak to be a pandemic. As the mosquito season progressed, the understandable concern that mosquitoes could transmit the virus began to increase among the general public and public health organisations. We have investigated the vector competence ofCulex pipiensandAedes albopictus, the two most common species of vector mosquitoes in Europe, for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Due to the very unusual feeding behaviour ofAe. albopictus, we also evaluated the role of this mosquito in a potential mechanical transmission of the virus.MethodsFor the vector competence study, mosquitoes were allowed to take several infectious blood meals. The mosquitoes were then collected and analysed at 0, 3, 7 and 10 days post-feeding. For the mechanical transmission test,Ae. albopictusfemales were allowed to feed for a short time on a feeder containing infectious blood and then on a feeder containing virus-free blood. Both mosquitoes and blood were tested for viral presence.ResultsCulex pipiensandAe. albopictuswere found not be competent vectors for SARS-CoV-2, andAe. albopictuswas unable to mechanically transmit the virus.ConclusionsThis is the first study to show that the most common species of vector mosquitoes in Europe do not transmit SARS-CoV-2 and thatAe. albopictusis unable to mechanically transmit the virus from a positive host to a healthy host through host-feeding.Graphical Abstract
Risk factors for lymphatic filariasis and mass drug administration non-participation in Mandalay Region, Myanmar
Authors: Dickson Benjamin F. R. , Graves Patricia M. , Aye Ni Ni , Nwe Thet Wai , Wai Tint , Win San San , Shwe Myint , Douglass Janet , Wood Peter , Wangdi Kinley , McBride William J. 
Published: January 2021

Abstract
Background
Myanmar commenced a lymphatic filariasis (LF) elimination programme in 2000. Whilst the country has made considerable progress since then, a number of districts have demonstrated persistent transmission after many rounds of mass drug administration (MDA). The causes of unsuccessful MDA have been examined elsewhere; however, there remains little information on the factors that contribute in Myanmar.

Methods
We conducted an analysis of factors associated with persistent infection, LF-related hydrocoele and MDA participation in an area with ongoing transmission in 2015. A cross-sectional household survey was undertaken in 24 villages across four townships of Mandalay Region. Participants were screened for circulating filarial antigen (CFA) using immunochromatographic tests and, if positive, for microfilaria by night-time thick blood slide. Individuals 15 year and older were assessed for filariasis morbidity (lymphoedema and, if male, hydrocoele) by ultrasound-assisted clinical examination. A pre-coded questionnaire was used to assess risk factors for LF and for non-participation (never taking MDA). Significant variables identified in univariate analyses were included in separate step-wise multivariate logistic regressions for each outcome.

Results
After adjustment for covariates and survey design, being CFA positive was significantly associated with age [odds ratio (OR) 1.03, 95% CI 1.01–1.06), per year], male gender (OR 3.14, 1.27–7.76), elevation (OR 0.96, 0.94–0.99, per metre) and the density of people per household room (OR 1.59, 1.31–1.92). LF-related hydrocoele was associated with age (OR 1.06, 1.03–1.09, per year) and residing in Amarapura Township (OR 8.93, 1.37–58.32). Never taking MDA was associated with male gender [OR 6.89 (2.13–22.28)] and age, particularly in females, with a significant interaction term. Overall, compared to those aged 30–44 years, the proportion never taking MDA was higher in all age groups (OR highest in those < 5 years and > 60 years, ranging from 3.37 to 12.82). Never taking MDA was also associated with residing in Amarapura township (OR 2.48, 1.15–5.31), moving to one’s current village from another (OR 2.62, 1.12–6.11) and ever having declined medication (OR 11.82, 4.25–32.91). Decreased likelihood of never taking MDA was associated with a higher proportion of household members being present during the last MDA round (OR 0.16, 0.03–0.74) and the number visits by the MDA programme (OR 0.69, 0.48–1.00).

Conclusions
These results contribute to the understanding of LF and MDA participation-related risk factors and will assist Myanmar to improve its elimination and morbidity management programmes.

Graphical Abstract
Gene co-expression network analysis of Trypanosoma brucei in tsetse fly vector
Authors: Mwangi Kennedy W. , Macharia Rosaline W. , Bargul Joel L. 
Published: January 2021

AbstractBackgroundTrypanosoma bruceispecies are motile protozoan parasites that are cyclically transmitted by tsetse fly (genusGlossina) causing human sleeping sickness and nagana in livestock in sub-Saharan Africa. African trypanosomes display digenetic life cycle stages in the tsetse fly vector and in their mammalian host. Experimental work on insect-stage trypanosomes is challenging because of the difficulty in setting up successfulin vitrocultures. Therefore, there is limited knowledge on the trypanosome biology during its development in the tsetse fly. Consequently, this limits the development of new strategies for blocking parasite transmission in the tsetse fly.MethodsIn this study, RNA-Seq data of insect-stage trypanosomes were used to construct aT. bruceigene co-expression network using the weighted gene co-expression analysis (WGCNA) method. The study identified significant enriched modules for genes that play key roles during the parasite’s development in tsetse fly. Furthermore, potential 3′ untranslated region (UTR) regulatory elements for genes that clustered in the same module were identified using the Finding Informative Regulatory Elements (FIRE) tool.ResultsA fraction of gene modules (12 out of 27 modules) in the constructed network were found to be enriched in functional roles associated with the cell division, protein biosynthesis, mitochondrion, and cell surface. Additionally, 12 hub genes encoding proteins such as RNA-binding protein 6 (RBP6), arginine kinase 1 (AK1),bruceialanine-rich protein (BARP), among others, were identified for the 12 significantly enriched gene modules. In addition, the potential regulatory elements located in the 3′ untranslated regions of genes within the same module were predicted.ConclusionsThe constructed gene co-expression network provides a useful resource for network-based data mining to identify candidate genes for functional studies. This will enhance understanding of the molecular mechanisms that underlie important biological processes during parasite’s development in tsetse fly. Ultimately, these findings will be key in the identification of potential molecular targets for disease control.Graphical Abstract
MSCR: multidimensional secure clustered routing scheme in hierarchical wireless sensor networks
Authors: Fang Weidong , Zhang Wuxiong , Chen Wei , Liu Jin , Ni Yepeng , Yang Yinxuan 
Published: January 2021

AbstractFor hierarchical wireless sensor network (WSN), the clustered routing protocol can effectively deal with large-scale application requirements, thereby, how to efficiently elect the secure cluster heads becomes very critical. Unfortunately, many current studies only focus on improving security while neglecting energy efficiency and transmission performance. In this paper, a lightweight trust management scheme (LTMS) is proposed based on binomial distribution for defending against the internal attacks. Simultaneously, distance domain, energy domain, security domain and environment domain are considered and introduced to propose a multidimensional secure clustered routing (MSCR) scheme by using dynamic dimension weight in hierarchical WSNs. The simulation results show that LTMS can effectively prevent a malicious node from being elected as a cluster head, and MSCR can achieve a balance between security, transmission performance and energy efficiency under the requirements of environmental applications.
DSSAM: digitally signed secure acknowledgement method for mobile ad hoc network
Authors: Srivastava Ashutosh , Gupta Sachin Kumar , Najim Mohd , Sahu Nitesh , Aggarwal Geetika , Mazumdar Bireshwar Dass 
Published: January 2021

AbstractMobile ad hoc network (MANET) is an infrastructure-less, self-motivated, arbitrary, self-configuring, rapidly changing, multi-hop network that is self-possessing wireless bandwidth-conscious links without centrally managed router support. In such a network, wireless media is easy to snoop. It is firm to the surety to access any node, easier to insertion of bad elements or attackers for malicious activities in the network. Therefore, security issues become one of the significant considerations for such kind of networks. The deployment of an effective intrusion detection system is important in order to provide protection against various attacks. In this paper, a Digitally Signed Secure Acknowledgement Method (DSSAM) with the use of the RSA digital signature has been proposed and simulated. Three different parameters are considered, namely secure acknowledgment, node authentication, and packet authentication for study. This article observes the DSSAM performance and compares it with two existing standard methods, namely Watchdog and 2-ACK under standard Dynamic Source Routing (DSR) routing environment. In the end, it is noticed that the rate of detection of malicious behaviour is better in the case of the proposed method. However, associated overheads are high. A trade-off between performance and overhead has been considered.