bluuebunny/crossref_metadata_2025_split huggingface dataset:
A new sequential animal model for infection-related non-unions with segmental bone defect
Authors: Helbig Lars , Guehring Thorsten , Titze Nadine , Nurjadi Dennis , Sonntag Robert , Armbruster Jonas , Wildemann Britt , Schmidmaier Gerhard , Gruetzner Alfred Paul , Freischmidt Holger 
Published: May 2020

AbstractBackgroundThe treatment of fracture-related infections (FRI) is still a challenge for orthopedic surgeons. The prevalence of FRI is particularly high in open fractures with extensive soft-tissue damage. This study aimed to develop a new two-step animal model for non-unions with segmental bone defects, which could be used to evaluate new innovative bone substitutes to improve the therapeutic options in humans with FRI and bone defects.MethodsAfter randomization to infected or non-infected groups, 30 Sprague-Dawley rats underwent a transverse osteotomy of the mid-shaft femur with a 5 mm defect. Additionally, the periosteum at the fracture zone was cauterized at both sides. After intramedullary inoculation with 103 CFUStaphylococcus aureus(infected group) or PBS (non-infected group), a fracture stabilization was done by intramedullary K-wires. After 5 weeks, the bone healing process was evaluated, and revision surgery was performed in order to obtain increased bone healing. The initial K-wires were removed, and debridement of the osteotomy-gap was done followed by a more stable re-osteosynthesis with an angle-stable plate. After further 8 weeks all rats were euthanized and the bone consolidation was tested biomechanically and the callus formation quantitatively by micro-CT analysis.ResultsWe developed and presented a new two-stage non-union animal model through a targetedS. aureusinfection. After 5 weeks, all animals showed a non-union irrespective of assignment to the infected and non-infected group. Lane and Sandhu score showed a higher callus formation in the infected group. In all infected animals, the inoculatedS. aureusstrain was detected in the revision surgery. The second surgery did not improve bone healing, as shown by the Lane Sandhu score and in the μ-CT analysis. Similarly, biomechanical testing showed in both groups a significantly lower maximum torque as compared to the contralateral side (p < 0.0001).ConclusionsWe were able to successfully develop a new two-stage non-union animal model, which reflects a genuine clinical situation of an infection-related non-union model with segmental bone defects. This model could be used to evaluate various therapeutic anti-infectious and osteoinductive strategies in FRIs.
A prospective observational cohort study of posterior tibial nerve stimulation in patients with multiple sclerosis: design and methods
Authors: Lane Giulia I. , Mao-Draayer Yang , Barboglio-Romo Paholo , Clemens J. Quentin , Gupta Priyanka , Dunn Rod , Qin Yongmei , Cameron Anne P. , Stoffel John T. 
Published: May 2020

Abstract
Background
Posterior tibial nerve stimulation (PTNS) is a promising treatment for lower urinary tract symptoms (LUTS) in patients with MS. However, long term data focusing on PTNS impact on health-related quality of life (HRQOL), bowel and bladder symptoms are lacking. This paper describes a study protocol that examines the extended efficacy of PTNS on MS related bladder and bowel symptoms and resulting HRQOL.

Methods/Design
This is a single-centered, prospective, longitudinal, observational cohort study of patients with MS who suffer from LUTS and are refractory to two prior treatment modalities. Participants who have elected to pursue PTNS therapy for LUTS will be eligible. The primary outcome is the median number of urinary frequency and incontinence episodes on a 3-day voiding diary at 3, 12 and 24 months compared to baseline. Secondary outcome measures will include change in total AUA-SS, M-ISI, NBSS, SF-12, SSS and BCS scores from baseline The Expanded Disability Status Scale and magnetic resonance imaging will be evaluated at baseline and annually throughout the study.

Discussion
This research protocol aims to expand on the existing literature regarding outcomes of PTNS in MS. Specifically, it will provide long term follow-up data on bladder, bowel, sexual and HRQOL outcomes. The completion of this study will provide longitudinal efficacy data of the impact of PTNS in MS patients.

Trial registration
NCT04063852.
Report: central diabetes insipidus and schwannoma in a male with X-linked congenital adrenal hypoplasia
Authors: Seo Boo Kyeong , Jeong Seul Ah. , Cho Jae Young , Park Ji Sook , Seo Ji-Hyun , Park Eun Sil , Lim Jae-Young , Woo Hyang-Ok , Youn Hee-Shang 
Published: May 2020

Abstract
Background
DAX1 mutations are related to the X-linked form of adrenal hypoplasia congenita (AHC) in infancy and to hypogonadotropic hypogonadism (HH) in puberty. We report a male patient affected by X-linked AHC who presented with central diabetes insipidus and schwannoma in adulthood, which has not been described in association with AHC.

Case presentation
A 36-day-old male infant who presented with severe dehydration was admitted to the intensive care unit. His laboratory findings showed hyponatremia, hyperkalemia, hypoglycemia, and metabolic acidosis. After hormonal evaluation, he was diagnosed with adrenal insufficiency, and he recovered after treatment with hydrocortisone and a mineralocorticoid. He continued to take hydrocortisone and the mineralocorticoid after discharge. At the age of 17, he did not show any signs of puberty. On the basis of a GnRH test, a diagnosis of HH was made. At the age of 24, he was hospitalized with thirst, polydipsia and polyuria. He underwent a water deprivation test for polydipsia and was diagnosed with central diabetes insipidus. By quantitative polymerase chain reaction analysis, we identified a hemizygous frameshift mutation in DAX1 (c.543delA).

Conclusions
We suggest that DAX1 mutations affect a wider variety of endocrine organs than previously known, including the posterior pituitary gland.
A combined individual and group-based stabilization and skill training intervention versus treatment as usual for patients with long lasting posttraumatic reactions receiving outpatient treatment in specialized mental health care – a study protocol for a randomized controlled trial
Authors: Holgersen K. H. , Brønstad I. , Jensen M. , Brattland H. , Reitan S. K. , Hassel A. M. , Arentz M. , Lara-Cabrera M. , Skjervold A. E. 
Published: May 2020

Abstract
Background
Suffering linked to previous interpersonal trauma is common among patients in mental health care. Diagnostic labels may vary, but the clinical picture is often characterized by long-lasting and complex psychological and somatic symptoms, subjective distress and reduced quality of health and life. A substantial proportion of patients do not recover after individual treatment in ordinary specialized mental healthcare settings, despite the proven usefulness of individual trauma-specific treatments. The therapeutic factors that arise in group settings, such as normalization, shame reduction and corrective relational experiences, may be particularly useful for trauma survivors. However, evidence in support of group treatment for trauma survivors is scarce. This study aims to test whether combining a novel group intervention to individual treatment is superior to conventional individual out-patient treatment in an ordinary community mental health hospital.

Methods
In a single-site, non-blinded, randomized controlled trial (RCT), the effect of a combined group-based stabilization and skill-training (SST) intervention added to individual treatment will be compared to conventional treatment (treatment as usual, TAU) alone. Participants (N = 160) with ongoing and long-lasting reactions related to known adverse life events from the past will be recruited among patients at general outpatient clinics in a community mental health centre at St. Olav’s University Hospital, Trondheim, Norway. Following baseline assessment and randomization, participants will complete follow-up measures at 4, 8, 13 and 19 months post-baseline. The primary outcome is personal recovery (The questionnaire about the process of recovery , QPR). Secondary outcomes include (1) self-reported symptoms of posttraumatic stress, general mental and somatic health symptoms, well-being, functional impairment and client satisfaction, (2) immunological and endocrine response measured in blood samples and (3) national registry data on occupational status, use of mental health services and pharmacological treatment. Additionally, mechanisms of change via posttraumatic cognitions will be examined.

Discussion
The addition of a group-based intervention to individual treatment for trauma survivors might prove to be an efficient way to meet the need of long-lasting high-intensity treatment in a large group of patients in mental health care, thereby reducing their suffering and increasing their psychosocial functioning.

Trial registration
ClinicalTrials.gov: NCT03887559. Registered on 25 March 2019.
The Medical Genome Initiative: moving whole-genome sequencing for rare disease diagnosis to the clinic
Authors:   on behalf of the Medical Genome Initiative, Marshall Christian R. , Bick David , Belmont John W. , Taylor Stacie L. , Ashley Euan , Dimmock David , Jobanputra Vaidehi , Kearney Hutton M. , Kulkarni Shashikant , Rehm Heidi 
Published: May 2020

AbstractClinical whole-genome sequencing (WGS) offers clear diagnostic benefits for patients with rare disease. However, there are barriers to its widespread adoption, including a lack of standards for clinical practice. The Medical Genome Initiative consortium was formed to provide practical guidance and support the development of standards for the use of clinical WGS.
Epidermal growth factor upregulates expression of MUC5AC via TMEM16A, in chronic rhinosinusitis with nasal polyps
Authors: Jiao Jian , Zhang Tao , Zhang Yu , Li Jingyun , Wang Min , Wang Ming , Li Ying , Wang Xiangdong , Zhang Luo 
Published: May 2020

AbstractBackgroundMucus hypersecretion and goblet cell upregulation are common features of chronic rhinosinusitis with nasal polyps (CRSwNP). Although epidermal growth factor (EGF) has been reported to stimulate the expression of MUC5AC, the major macro-molecular constituent of airway mucus, the precise mechanisms underlying the regulation of MUC5AC expression are still not fully understood. The aim of this study therefore was to investigate the role of EGF in regulation of mucin MUC5AC expression and define the involvement of transmembrane protein 16A (TMEM16A) in mediating the EGF-induced mucus overexpression.MethodsHuman nasal epithelial cells (HNECs) derived from tissue of patients with CRSwNP and control subjects were established as air–liquid interface (ALI) cultures. Differentiated cultures were treated with different concentrations of EGF for 4–24 h, and assessed for the expression of TMEM16A and MUC5AC by real-time RT-PCR, Western blotting, ELISA and immunofluorescence. Cultures pretreated for 30 min with T16Ainh-A01 (a specific TMEM16A inhibitor) or LY294002 (a phosphoinositide 3-kinase (PI3K) inhibitor) were also assessed similarly following EGF treatment.ResultsEGF treatment (10–100 ng/ml for 4–24 h) significantly increased the expression of both TMEM16A and MUC5AC mRNA and protein, as well as the percentage of TMEM16A-positive cells, MUC5AC-positive cells and cells coexpressing TMEM16A and MUC5AC in HNECs compared to control non-EGF-treated HNECs. Pretreatment of the HNECs with T16Ainh-A01 and LY294002 attenuated these EGF-induced effects.ConclusionsThis study demonstrated that EGF upregulates the expression of MUC5AC in HNECs from CRSwNP patients. Furthermore, the EGF-mediated regulation of MUC5AC expression is likely to involve a PI3K-TMEM16A signalling pathway in CRSwNP.
Dysregulation of protein synthesis and dendritic spine morphogenesis in ASD: studies in human pluripotent stem cells
Authors: Lo Louisa Hoi-Ying , Lai Kwok-On 
Published: May 2020

AbstractAutism spectrum disorder (ASD) is a brain disorder that involves changes in neuronal connections. Abnormal morphology of dendritic spines on postsynaptic neurons has been observed in ASD patients and transgenic mice that model different monogenetic causes of ASD. A number of ASD-associated genetic variants are known to disrupt dendritic local protein synthesis, which is essential for spine morphogenesis, synaptic transmission, and plasticity. Most of our understanding on the molecular mechanism underlying ASD depends on studies using rodents. However, recent advance in human pluripotent stem cells and their neural differentiation provides a powerful alternative tool to understand the cellular aspects of human neurological disorders. In this review, we summarize recent progress on studying mRNA targeting and local protein synthesis in stem cell-derived neurons, and discuss how perturbation of these processes may impact synapse development and functions that are relevant to cognitive deficits in ASD.
International Hip Outcome Tool (12-items) as health-related quality-of-life measure in osteoarthritis: validation of Greek version
Authors: Stasi Sophia , Stamou Magdalini , Papathanasiou George , Frantzeskaki Paraskevi , Kanavas Emmanouil , Evaggelou-Sossidis George , Gouskos Adamantios , Palantzas Andreas , Poursanidis Kyriakos , Macheras George A. 
Published: May 2020

Abstract
Background
The 12-item International Hip Outcome Tool (iHOT12) is a patient-reported outcome (PRO) designed to evaluate quality of life. We assessed the psychometric properties of the Greek version (iHOT12-Gr) in hip osteoarthritic patients.

Methods
Data from 124 patients aged > 50 years were used for factor analysis. Reliability evaluation included internal consistency, test-retest reliability, and interpretability. Content validity was examined by calculating the item-level content validity indices (I-CVI) and the scale-level content validity indices (S-CVI), using two methods: S-CVI Average (S-CVI/Ave), and the S-CVI Universal Agreement among experts (S-CVI/UA). Construct validity was tested against Greek versions of the Lower Extremity Functional Scale (LEFS-Greek), Modified Harris Hip Score (MHHS-Gr), and the 30 s chair-to-stand, Timed Up & Go (TUG), and 9-stairs-ascend/descend (9S-A/D) tests. Known-groups validity was examined using LEFS-Greek (cut-off = 53 points) as estimate variable. Responsiveness was examined pre and post total hip arthroplasty (4 and 8 weeks).

Results
Factor analysis revealed a two-factor model. Factor-1 (items 1–9) reflects “Symptoms and functionality”, while Factor-2 (items 10–12) reflects “Hip disorder-related concerns”. Reliability: Internal consistency and test-retest reliability of iHOT12-Gr-total were excellent: Cronbach’s alpha > 0.92 and ICC(95% CI) > 0.976(0.96–0.99)(p < 0.001). Interpretability: There was no floor or ceiling effect; measurement error: 3.72 (Factor-1), 3.64 (Factor-2), and 3.22 (iHOT12-Gr-total); minimal detectable change: 10.3 (Factor-1), 10.1 (Factor-2), and 8.92 (iHOT12-Gr-total). Validity: Content validity: The I-CVI value of the 12 items ranged from 1.00 to 0.83, the S-CVI/Ave was 0.97 and the S-CVI/UA was 0.83. Construct validity: iHOT12-Gr correlated strongly with both LEFS-Greek and MHHS-Gr, and weakly but significantly with 30s chair-to-stand, TUG and 9S-A/D (p < 0.001). Known-groups validity showed that iHOT12-Gr well discriminated subgroups of patients (p < 0.001). ROC analysis cut-off points were 51.9 (Factor-1), 25 (Factor-2) and 45.2 (iHOT12-Gr-total) (p < 0.001). Responsiveness: Four and 8 weeks postoperatively, standardized response means of Factor-1, Factor-2, and iHOT12-Gr-total were > 0.8.

Conclusion
iHOT12-Gr showed excellent reliability properties. The content validity was excellent and significant weak-to-strong correlations were found regarding construct validity. The known-group validity was also significant, while the responsiveness was excellent. iHOT12-Gr could be a reliable and valid PRO for assessing quality of life in patients with hip osteoarthritis.
The role of advanced MRI in the development of treat-to-target therapeutic strategies, patient stratification and phenotyping in rheumatoid arthritis
Authors: Mobasheri Ali , Hinton Mark , Shaikh Faiq , Kubassova Olga 
Published: May 2020

AbstractIn this commentary, we discuss the potential of advanced imaging, particularly Dynamic Contrast Enhanced (DCE) magnetic resonance imaging (MRI) for the objective assessment of the inflammatory process in rheumatoid arthritis (RA). We emphasise the potential of DCE-MRI in advancing the field and exploring new areas of research and development in RA. We hypothesize that different grades of bone marrow edema (BME) and synovitis in RA can be examined and monitored in a more sensitive manner with DCE-MRI. Future treatments for RA may benefit from the application of enhanced imaging of BMEs and synovitis. DCE-MRI may also facilitate enhanced stratification and phenotyping of patients enrolled in clinical trials.
Learning to rebel
Authors: Luna Elsie , Mearman Andrew 
Published: May 2020

Abstract
Background
As a response to collective failure to move adequately towards sustainability, youth movements have grown. This article explores the experiences of one young climate activist, Elsie Luna. The article is the product of conversations between the co-authors, augmented by written material by Elsie Luna. The article seeks to avoid adultism, that is, the power that adults have over children; hence it is written principally using Elsie’s own words, with minimal translation or interpretation. The article reflects on three key recent events in Elsie Luna’s activism: her approach to the London headquarters of several oil companies; her ‘dying’ symbolically at the BBC in Berlin; and her recent involvement in the large Extinction Rebellion actions in London.

Findings
The article suggests that these events offer insights on learning. Specifically, she is formulating views on sustainability, on system change and associated strategies, and developing a moral position on these matters. She has learned socially, from family and other immediate influences, and from activism. Thus, further, she has learned from experience, but has done so in her own self-managed way.
Rapid guide to the management of cardiac patients during the COVID-19 pandemic in Egypt: “a position statement of the Egyptian Society of Cardiology”
Authors: Shaheen Sameh , Awwad Omar , Shokry Khalid , Abdel-Hamid Magdy , El-Etriby Adel , Hasan-Ali Hosam , Shawky Islam , Magdy Ahmad , Nasr Gamila , Kabil Hamza , Elhadidy Amr , Zaki Mohamad , Hegab Ahmad 
Published: May 2020

AbstractCOVID-19 pandemic poses an enormous challenge to healthcare system in Egypt. This document is a position statement from the Egyptian Society of Cardiology. It aims to provide information to cardiovascular healthcare providers in Egypt to guarantee delivery of qualitypatient careand ensure adequate levels ofprotectionagainst infection during the COVID-19 pandemic. Older patients and those with cardiovascular disease are at higher risk of mortality. The current situation requires unusual allocation of resources which may negatively impact the care of patients with cardiovascular disease. Cardiologists should be prepared in the COVID-19 pandemic. The challenge is in providing the best quality of care despite limited resources while keeping all medical staff as safe as possible. Consider deferring elective procedures whenever possible. All medical staff should undergo rigorous training on infection control and the use of high-quality personal protection equipment. Cardiologists should promote telemedicine in the outpatient setting, prioritize outpatient contacts, and avoid nosocomial dissemination of the virus to patients and healthcare providers. A much conservative approach for emergent cardiac patients is recommended, and invasive interventions are reserved for high risk hemodynamically unstable patients. During the pandemic, the most important principles of treatment should be controlling the spread of infection as the first priority, prompt assessment of patient risk, recommending conservative medical therapy rather than invasive interventions, and strict infection control measures to limit infection spread within the hospital and to healthcare workers.
Atypical central neurocytoma with leptomeningeal dissemination: a case report
Authors: Goyal Shikha , Kataria Tejinder , Gupta Deepak , Dhyani Aruj , Mohapatra Ishani , Narang Karanjit Singh 
Published: May 2020

Abstract
Background
Central neurocytomas represent 0.25–0.5% of all intracranial tumors in adults. Leptomeningeal spread is uncommon, and the exact incidence of meningeal spread is unknown due to sparse literature. We present the clinical course and management outcome of a case of atypical central neurocytoma with leptomeningeal spread.

Case presentation
A young gentleman, who initially presented with memory loss, was found to have a right intra-axial periventricular mass on imaging. He underwent subtotal resection, and operative histopathology suggested a periventricular atypical neurocytoma. In view of subtotal resection, adjuvant focal radiation therapy was recommended, but he developed headache and blurring of vision 10 days postoperatively. Contrast enhanced craniospinal magnetic resonance imaging (MRI) showed residual primary tumor as well as diffuse leptomeningeal spread. Cerebrospinal fluid cytology also showed malignant cells. After tumor board discussion, craniospinal axis irradiation was advised and delivered. He remained disease-free for 10 months after radiation therapy, but then developed local and spinal recurrence, and offered salvage chemotherapy. His general condition deteriorated following chemotherapy with disease progression, and he was subsequently advised best supportive care.

Conclusion
Leptomeningeal dissemination in atypical neurocytomas portends an aggressive course and adverse prognosis; management decisions may need tailoring as per individual presentation.
Association of polymorphisms in metastasis suppressor genes NME1 and KISS1 with breast cancer development and metastasis
Authors: Antar Sarah , Mokhtar Naglaa , Abd elghaffar Mahmoud Adel , Seleem Amal K. 
Published: May 2020

Abstract
Background
NME1 and KISS1 genes are two tumor metastasis suppressor genes, mapped to chromosomes 17q21.3 and 1q32 respectively. Here, we analyzed the association of EcoR1 (rs34214448—G/T) polymorphism in NME1 gene and 9 del T (rs5780218—A/-) polymorphism in KISS1 gene with breast cancer development and metastasis.

Results
The study included 75 women newly diagnosed with breast cancer recruited from Oncology Center at Mansoura University Hospitals and 37 age-matched healthy female volunteers as a control group. DNA was extracted from peripheral blood samples and genotyping of rs34214448 and rs5780218 SNPs was carried out by PCR-RFLP technique. NME1 EcoR1 (rs34214448) polymorphism has a statistically significant association with breast cancer risk (P < 0.001). Most of breast cancer group (55%) had heterozygous (G/T) genotype while most of control group (95%) had homozygous wild (G/G) genotype (P < 0.0005). Also, KISS1 rs5780218 polymorphism has a statistically significant association with breast cancer risk. The wild (A/A) genotype was associated with lower risk of breast cancer (A/- + -/- vs. A/A: OR = 3.1, 95% CI = 1.15–8.36, P = 0.025). EcoR1 (rs34214448) polymorphism revealed a significant association with tumor stage and distant metastasis as patients. Carriers of the wild (G/G) genotype were more likely to present with advanced disease stages and distant metastasis.

Conclusions
Both EcoR1 (rs34214448) polymorphism of NME1 gene and rs5780218 polymorphism of KISS1 gene revealed significant association with increased risk of breast cancer development. The (G/G) genotype of EcoR1 polymorphism was associated with higher risk of breast cancer metastasis.