bluuebunny/crossref_metadata_2025_split huggingface dataset:
Constructing cancer patient-specific and group-specific gene networks with multi-omics data
Authors: Lee Wook , Huang De-Shuang , Han Kyungsook 
Published: August 2020

Abstract
Background
Cancer is a complex and heterogeneous disease with many possible genetic and environmental causes. The same treatment for patients of the same cancer type often results in different outcomes in terms of efficacy and side effects of the treatment. Thus, the molecular characterization of individual cancer patients is increasingly important to find an effective treatment. Recently a few methods have been developed to construct cancer sample-specific gene networks based on the difference in the mRNA expression levels between the cancer sample and reference samples.

Methods
We constructed a patient-specific network with multi-omics data based on the difference between a reference network and a perturbed reference network by the patient. A network specific to a group of patients was obtained using the average change in correlation coefficients and node degree of patient-specific networks of the group.

Results
In this paper, we present a new method for constructing cancer patient-specific and group-specific gene networks with multi-omics data. The main differences of our method from previous ones are as follows: (1) networks are constructed with multi-omics (mRNA expression, copy number variation, DNA methylation and microRNA expression) data rather than with mRNA expression data alone, (2) background networks are constructed with both normal samples and cancer samples of the specified type to extract cancer-specific gene correlations, and (3) both patient individual-specific networks and patient group-specific networks can be constructed. The results of evaluating our method with several types of cancer show that it constructs more informative and accurate gene networks than previous methods.

Conclusions
The results of evaluating our method with extensive data of seven cancer types show that the difference of gene correlations between the reference samples and a patient sample is a more predictive feature than mRNA expression levels and that gene networks constructed with multi-omics data show a better performance than those with single omics data in predicting cancer for most cancer types. Our approach will be useful for finding genes and gene pairs to tailor treatments to individual characteristics.
Clinically relevant radioresistant rhabdomyosarcoma cell lines: functional, molecular and immune-related characterization
Authors: Petragnano Francesco , Pietrantoni Ilaria , Camero Simona , Codenotti Silvia , Milazzo Luisa , Vulcano Francesca , Macioce Giampiero , Giordani Ilenia , Tini Paolo , Cheleschi Sara , Gravina Giovanni Luca , Festuccia Claudio , Rossetti Alessandra , Delle Monache Simona , Ordinelli Alessandra , Ciccarelli Carmela , Mauro Annunziata , Barbara Barboni , Antinozzi Cristina , Schiavetti Amalia , Maggio Roberto , Di Luigi Luigi , Polimeni Antonella , Marchese Cinzia , Tombolini Vincenzo , Fanzani Alessandro , Bernabò Nicola , Megiorni Francesca , Marampon Francesco 
Published: August 2020

Abstract
Background
The probability of local tumor control after radiotherapy (RT) remains still miserably poor in pediatric rhabdomyosarcoma (RMS). Thus, understanding the molecular mechanisms responsible of tumor relapse is essential to identify personalized RT-based strategies. Contrary to what has been done so far, a correct characterization of cellular radioresistance should be performed comparing radioresistant and radiosensitive cells with the same isogenic background.

Methods
Clinically relevant radioresistant (RR) embryonal (RD) and alveolar (RH30) RMS cell lines have been developed by irradiating them with clinical-like hypo-fractionated schedule. RMS-RR cells were compared to parental isogenic counterpart (RMS-PR) and studied following the radiobiological concept of the “6Rs”, which stand for repair, redistribution, repopulation, reoxygenation, intrinsic radioresistance and radio-immuno-biology.

Results
RMS-RR cell lines, characterized by a more aggressive and in vitro pro-metastatic phenotype, showed a higher ability to i) detoxify from reactive oxygen species; ii) repair DNA damage by differently activating non-homologous end joining and homologous recombination pathways; iii) counteract RT-induced G2/M cell cycle arrest by re-starting growth and repopulating after irradiation; iv) express cancer stem-like profile. Bioinformatic analyses, performed to assess the role of 41 cytokines after RT exposure and their network interactions, suggested TGF-β, MIF, CCL2, CXCL5, CXCL8 and CXCL12 as master regulators of cancer immune escape in RMS tumors.

Conclusions
These results suggest that RMS could sustain intrinsic and acquire radioresistance by different mechanisms and indicate potential targets for future combined radiosensitizing strategies.
Maternal and infant outcomes in sarcoidosis pregnancy: a Swedish population-based cohort study of first births
Authors: Köcher Laura , Rossides Marios , Remaeus Katarina , Grunewald Johan , Eklund Anders , Kullberg Susanna , Arkema Elizabeth V. 
Published: August 2020

AbstractBackgroundIt is unclear whether sarcoidosis, a multisystem inflammatory disease, is associated with adverse pregnancy outcomes. We aimed to assess the risk of adverse maternal and infant outcomes in sarcoidosis pregnancies, focused on first births.MethodsUsing a population-based cohort study design and Swedish national registers (2002–2013), we identified 182 singleton first pregnancies in the Medical Birth Register with at least two maternal ICD-coded sarcoidosis visits prior to pregnancy in the National Patient Register. Modified Poisson regression models estimated relative risks (RR) of adverse outcomes in sarcoidosis pregnancies compared to the general population adjusted for maternal age at delivery, calendar year and educational level. Some models were additionally adjusted for maternal body mass index and smoking status.ResultsThe prevalence of pre-existing diabetes and hypertension was higher in mothers with sarcoidosis than those without sarcoidosis. Mothers with sarcoidosis had an increased risk of preeclampsia/eclampsia (RR 1.6; 95%CI 1.0, 2.6) and cesarean delivery (RR 1.3; 95%CI 1.0, 1.6). There were < 5 stillbirths and cases of infection and no cases of placental abruption, venous thromboembolism, cardiac arrest or maternal death. Newborns of first-time mothers with sarcoidosis had a 70% increased risk of preterm birth (RR 1.7; 95%CI 1.1, 2.5). There was an increased risk of birth defects (RR 1.6; 95%CI 0.9, 2.8) the majority of which were non-cardiac.ConclusionsSarcoidosis is associated with increased risks for preeclampsia/eclampsia, cesarean delivery, preterm birth and some birth defects. Awareness of these conditions may prevent possible pregnancy complications in mothers with sarcoidosis and their newborns.
Prevalence and determinants of malaria infection among children of local farmers in Central Malawi
Authors: Chilanga Emmanuel , Collin-Vézina Delphine , MacIntosh Heather , Mitchell Claudia , Cherney Katrina 
Published: August 2020

AbstractBackgroundMalaria is a leading cause of morbidity and mortality among children under 5 years in Malawi, and especially among those from rural areas of central Malawi. The goal of this study was to examine the prevalence and determinants of malaria infection among children in rural areas of Dowa district in central Malawi.MethodsA multistage, cross-sectional study design was used to systematically sample 523 child-mother dyads from postnatal clinics. A survey was administered to mothers and a rapid malaria infection diagnostic test was administered to children. The main outcome was positive malaria diagnostic tests in children. Logistic regressions were used to determine risk factors associated with malaria among children aged 2 to 59 months.ResultsThe prevalence of malaria among children under 5 years was 35.4%. Results suggest that children of mothers who experienced recent intimate partner violence (IPV) were more likely to be diagnosed with malaria (AOR: 1.88, 95% CI 1.19–2.97;P = 0.007) than children of mothers who did not. Children of mothers who had no formal education were more likely to be diagnosed with malaria (AOR: 2.77, 95% CI 1.24–6.19;P = 0.013) than children of mothers who had received secondary education. Children aged 2 to 5 months and 6 to 11 months were less likely to be diagnosed with malaria (AOR: 0.21, 95% CI 0.10–0.46;P = 0.000 and AOR: 0.43; 95% CI 0.22–0.85;P = 0.016, respectively) than children aged 24 to 59 months.ConclusionThe prevalence of malaria infection among children in the study area was comparable to the national level. In addition to available malaria control programmes, further attention should be paid to children whose mothers have no formal education, children aged 24 to 59 months, and children of mothers that are exposed to IPV in the area.
Engaging parents in digital sexual and reproductive health education: evidence from the JACK trial
Authors: Aventin Áine , Gough Aisling , McShane Theresa , Gillespie Kathryn , O’Hare Liam , Young Honor , Lewis Ruth , Warren Emily , Buckley Kelly , Lohan Maria 
Published: August 2020

Abstract
Background
Research evidence and international policy highlight the central role that parents play in promoting positive sexual behaviour and outcomes in their children, however they can be difficult to engage in sexual and reproductive health (SRH) education programmes. Digital health promotion that uses online and mobile technologies (OMTs) to promote parent-child communication may offer an innovative solution to reach parents, however, few programmes have used OMTs to involve parents in SRH, and none have reported lessons learned in relation to optimising engagement. This study addresses this gap in the literature by reporting acceptability and feasibility of using OMTs to engage parents in SRH education. Findings will be relevant for those wishing to develop and implement digital SRH programmes with parents internationally.

Methods
The Jack Trial is a UK-wide cluster randomised controlled trial recruiting over 8000 adolescents from 66 socially and religiously diverse post-primary schools. An embedded mixed-methods process evaluation explored user engagement with parent components of the If I Were Jack SRH education programme, which include online animated films and a parent-teen homework exercise.

Results
A total of 109 adolescents, teachers, parents and SRH policy experts took part in semi-structured interviews and focus groups, 134 parents responded to an online survey, and 3179 adolescents completed a programme engagement and satisfaction questionnaire. Parents who accessed the materials were positive about them; 87% rated them as ‘good or excellent’ and 67% said they helped them have conversations with their child about SRH. Web analytics revealed that 27% of contacted parents accessed the digital materials, with 9% viewing the animated films. Only 38% of teachers implemented the homework exercise, mainly because they assumed that students would not complete it or it might result in backlash from parents.

Conclusions
While digital parental materials show promise for engaging parents in SRH education, this study suggests that in order to optimise engagement, parental components that give parents the necessary skills to have conversations with their children about sex should be coupled with efforts to increase school and teacher confidence to communicate with parents on sensitive topics.

Trial registration
ISRCTN99459996.
Multicentre clinical radiotherapy audit in rectal cancer: results of the IROCA project
Authors: Fundowicz Magdalena , Aguiar Artur , de Castro Carla Lopes , Torras Maria Glòria , Deantonio Letizia , Konstanty Ewelina , Kruszyna-Mochalska Marta , Macia Miquel , Canals Eugeni , Caro Monica , Pisani Carla , Zwierzchowska Dorota , Molero Jaume , Eraso Arantxa , Lencart Joana , Muñoz-Montplet Carles , Carvalho Luisa , Krengli Marco , Malicki Julian , Guedea Ferran 
Published: August 2020

Abstract
Purpose
To perform a clinical audit to assess adherence to standard clinical practice for the diagnosis, treatment, and follow-up of patients undergoing radiotherapy for rectal cancer treatment in four European countries.

Materials and methods
Multi-institutional, retrospective cohort study of 221 patients treated for rectal cancer in 2015 at six European cancer centres. Clinical indicators applicable to general radiotherapy processes were evaluated. All data were obtained from electronic medical records.

Results
The audits were performed in the year 2017. We found substantial inter-centre variability in adherence to standard clinical practices: 1) presentation of cases at departmental clinical sessions (range, 0–100%) or multidisciplinary tumour board (50–95%); 2) pretreatment MRI (61.5–100%) and thoracoabdominal CT (15.0–100%). Large inter-centre differences were observed in the mean interval between biopsy and first visit to the radiotherapy department (range, 21.6–58.6 days) and between the first visit and start of treatment (15.1–38.8 days). Treatment interruptions ≥ 1 day occurred in 43.9% (2.5–90%) of cases overall. Treatment compensation was performed in 2.1% of cases. Treatment was completed in the prescribed time in 55.7% of cases.

Conclusions
This multi-institutional clinical audit revealed that most centres adhered to standard clinical practices for most of the radiotherapy processes-related variables assessed. However, the audit revealed marked inter-centre variability for certain quality indicators, particularly inconsistent record keeping. Multiple targets for improvement and/or harmonisation were identified, confirming the value of routine clinical audits to detect potential deviations from standard clinical practice.
Patient and surgical prognostic factors for inpatient functional recovery following THA and TKA: a prospective cohort study
Authors: Hewlett-Smith Nicola A. , Pope Rodney P. , Hing Wayne A. , Simas Vini P. , Furness James W. 
Published: August 2020

Abstract
Background
The introduction of enhanced recovery pathways has demonstrated both patient and organisational benefits. However, enhanced recovery pathways implemented for total hip arthroplasty (THA) and total knee arthroplasty (TKA) vary between health-care organisations, as do their measures of success, particularly patient-related outcomes. Despite inpatient functional recovery being essential for safe and timely hospital discharge, there is currently no gold standard method for its assessment, and the research undertaken to establish prognostic factors is limited. This study aimed to identify prognostic factors and subsequently develop prognostic models for inpatient functional recovery following primary, unilateral THA and TKA; identify factors associated with acute length of stay; and assess the relationships between inpatient function and longer-term functional outcomes.

Methods
Correlation and multiple regression analyses were used to determine prognostic factors for functional recovery (assessed using the modified Iowa Level of Assistance Scale on day 2 post-operatively) in a prospective cohort study of 354 patients following primary, unilateral THA or TKA.

Results
For the overall cohort and TKA group, significant prognostic factors included age, sex, pre-operative general health, pre-operative function, and use of general anaesthesia, local infiltration analgesia, and patient-controlled analgesia. In addition, arthroplasty site was a prognostic factor for the overall cohort, and surgery duration was prognostic for the TKA group. For the THA group, significant prognostic factors included pre-operative function, Risk Assessment and Prediction Tool score, and surgical approach. Several factors were associated with acute hospital length of stay. Inpatient function was positively correlated with functional outcomes assessed at 6 months post-operatively.

Conclusions
Prognostic models may facilitate the prediction of inpatient flow thus optimising organisational efficiency. Surgical prognostic factors warrant consideration as potential key elements in enhanced recovery pathways, associated with early post-operative functional recovery. Standardised measures of inpatient function serve to evaluate patient-centred outcomes and facilitate the benchmarking and improvement of enhanced recovery pathways.
Increasing the level of cytoskeletal protein Flightless I reduces adhesion formation in a murine digital flexor tendon model
Authors: Jackson Jessica E. , Kopecki Zlatko , Anderson Peter J. , Cowin Allison J. 
Published: August 2020

AbstractBackgroundSurgical repair of tendons is common, but function is often limited due to the formation of flexor tendon adhesions which reduce the mobility and use of the affected digit and hand. The severity of adhesion formation is dependent on numerous cellular processes many of which involve the actin cytoskeleton. Flightless I (Flii) is a highly conserved cytoskeletal protein, which has previously been identified as a potential target for improved healing of tendon injuries. Using human in vitro cell studies in conjunction with a murine model of partial laceration of the digital flexor tendon, we investigated the effect of modulating Flii levels on tenocyte function and formation of adhesions.MethodsHuman tenocyte proliferation and migration was determined using WST-1 and scratch wound assays following Flii knockdown by siRNA in vitro. Additionally, mice with normal and increased levels of Flii were subjected to a partial laceration of the digital flexor tendon in conjunction with a full tenotomy to immobilise the paw. Resulting adhesions were assessed using histology and immunohistochemistry for collagen I, III, TGF-β1and -β3ResultsFlii knockdown significantly reduced human tenocyte proliferation and migration in vitro. Increasing the expression of Flii significantly reduced digital tendon adhesion formation in vivo which was confirmed through significantly smaller adhesion scores based on collagen fibre orientation, thickness, proximity to other fibres and crimping. Reduced adhesion formation was accompanied with significantly decreased deposition of type I collagen and increased expression of TGF-β1 in vivo.ConclusionsThese findings suggest that increasing the level of Flii in an injured tendon may be beneficial for decreasing tendon adhesion formation.
CNS axonal degeneration and transport deficits at the optic nerve head precede structural and functional loss of retinal ganglion cells in a mouse model of glaucoma
Authors: Maddineni Prabhavathi , Kasetti Ramesh B. , Patel Pinkal D. , Millar J. Cameron , Kiehlbauch Charles , Clark Abbot F. , Zode Gulab S. 
Published: August 2020

Abstract
Background
Glaucoma is a leading neurodegenerative disease affecting over 70 million individuals worldwide. Early pathological events of axonal degeneration and retinopathy in response to elevated intraocular pressure (IOP) are limited and not well-defined due to the lack of appropriate animal models that faithfully replicate all the phenotypes of primary open angle glaucoma (POAG), the most common form of glaucoma. Glucocorticoid (GC)-induced ocular hypertension (OHT) and its associated iatrogenic open-angle glaucoma share many features with POAG. Here, we characterized a novel mouse model of GC-induced OHT for glaucomatous neurodegeneration and further explored early pathological events of axonal degeneration in response to elevated IOP.

Methods
C57BL/6 J mice were periocularly injected with either vehicle or the potent GC, dexamethasone 21-acetate (Dex) once a week for 10 weeks. Glaucoma phenotypes including IOP, outflow facility, structural and functional loss of retinal ganglion cells (RGCs), optic nerve (ON) degeneration, gliosis, and anterograde axonal transport deficits were examined at various stages of OHT.

Results
Prolonged treatment with Dex leads to glaucoma in mice similar to POAG patients including IOP elevation due to reduced outflow facility and dysfunction of trabecular meshwork, progressive ON degeneration and structural and functional loss of RGCs. Lowering of IOP rescued Dex-induced ON degeneration and RGC loss, suggesting that glaucomatous neurodegeneration is IOP dependent. Also, Dex-induced neurodegeneration was associated with activation of astrocytes, axonal transport deficits, ON demyelination, mitochondrial accumulation and immune cell infiltration in the optic nerve head (ONH) region. Our studies further show that ON degeneration precedes structural and functional loss of RGCs in Dex-treated mice. Axonal damage and transport deficits initiate at the ONH and progress toward the distal end of ON and target regions in the brain (i.e. superior colliculus). Most of anterograde transport was preserved during initial stages of axonal degeneration (30% loss) and complete transport deficits were only observed at the ONH during later stages of severe axonal degeneration (50% loss).

Conclusions
These findings indicate that ON degeneration and transport deficits at the ONH precede RGC structural and functional loss and provide a new potential therapeutic window for rescuing neuronal loss and restoring health of damaged axons in glaucoma.
Longitudinal changes of inflammatory parameters and their correlation with disease severity and outcomes in patients with COVID-19 from Wuhan, China
Authors: Zeng Zhilin , Yu Haijing , Chen Huilong , Qi Weipeng , Chen Liang , Chen Guang , Yan Weiming , Chen Tao , Ning Qin , Han Meifang , Wu Di 
Published: August 2020

Abstract
Background
Coronavirus disease 2019 (COVID-19) is a newly emerging infectious disease and rapidly escalating epidemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The pathogenesis of COVID-19 remains to be elucidated. We aimed to clarify correlation of systemic inflammation with disease severity and outcomes in COVID-19 patients.

Methods
In this retrospective study, baseline characteristics, laboratory findings, and treatments were compared among 317 laboratory-confirmed COVID-19 patients with moderate, severe, or critically ill form of the disease. Moreover, the longitudinal changes of serum cytokines, lactate dehydrogenase (LDH), high-sensitivity C-reactive protein (hsCRP), and hsCRP to lymphocyte count ratio (hsCRP/L) as well as their associations with disease severity and outcomes were investigated in 68 COVID-19 patients.

Results
Within 24 h of admission, the critically ill patients showed higher concentrations of inflammatory markers including serum soluble interleukin (IL)-2 receptor, IL-6, IL-8, IL-10, tumor necrosis factor alpha (TNF-α), ferritin, procalcitonin, LDH, hsCRP, and hsCRP/L than patients with severe or moderate disease. The severe cases displayed the similar response patterns when compared with moderate cases. The longitudinal assays showed the levels of pro-inflammatory cytokines, LDH, hsCRP, and hsCRP/L gradually declined within 10 days post admission in moderate, severe cases or those who survived. However, there was no significant reduction in cytokines, LDH, hsCRP, and hsCRP/L levels in critically ill or deceased patients throughout the course of illness. Compared with female patients, male cases showed higher serum concentrations of soluble IL-2R, IL-6, ferritin, procalcitonin, LDH, and hsCRP. Multivariate logistic regression analysis revealed that IL-6 > 50 pg/mL and LDH > 400 U/L on admission were independently associated with disease severity in patients with COVID-19.

Conclusion
Exuberant inflammatory responses within 24 h of admission in patients with COVID-19 may correlate with disease severity. SARS-CoV-2 infection appears to elicit a sex-based differential immune response. IL-6 and LDH were independent predictive parameters for assessing the severity of COVID-19. An early decline of these inflammation markers may be associated with better outcomes.