bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeted DNA Methylation Profiling of Human Cardiac Tissue Reveals Novel Epigenetic Traits and Gene Deregulation Across Different Heart Failure Patient Subtypes
Authors: Glezeva Nadezhda , Moran Bruce , Collier Patrick , Moravec Christine S. , Phelan Dermot , Donnellan Eoin , Russell-Hallinan Adam , O’Connor Darran P. , Gallagher William M. , Gallagher Joe , McDonald Kenneth , Ledwidge Mark , Baugh John , Das Sudipto , Watson Chris J. 
Published: February 2019

Background:
Limited knowledge exists of the extent of epigenetic alterations, such as DNA methylation, in heart failure (HF). We conducted targeted DNA methylation sequencing to identify DNA methylation alterations in coding and noncoding RNA (ncRNA) across different etiological subtypes of HF.

Methods and Results:

A targeted bisulfite sequence capture sequencing platform was applied to DNA extracted from cardiac interventricular septal tissue of 30 male HF patients encompassing causes including hypertrophic obstructive cardiomyopathy, ischemic cardiomyopathy, dilated cardiomyopathy, and 9 control patients with nonfailing hearts. We detected 62 678 differentially methylated regions in the studied HF cohort. By comparing each HF subgroup to the nonfailing control group, we identified 195 unique differentially methylated regions: 5 in hypertrophic obstructive cardiomyopathy, 151 in dilated cardiomyopathy, and 55 in ischemic cardiomyopathy. These translated to 4 genes/1 ncRNA in hypertrophic obstructive cardiomyopathy, 131 genes/17 ncRNA in dilated cardiomyopathy, and 51 genes/5 ncRNA in ischemic cardiomyopathy. Subsequent gene/ncRNA expression analysis was assessed using quantitative reverse transcription polymerase chain reaction and revealed 6 genes: 4 hypermethylated (
HEY2
,
MSR1
,
MYOM3
, and
COX17
), 2 hypomethylated (
CTGF
and
MMP2
); and 2 microRNA: 1 hypermethylated (miR-24-1), 1 hypomethylated (miR-155) with significantly upregulated or downregulated expression levels consistent with the direction of methylation in the particular HF subgroup.

Conclusions:
For the first time DNA methylation alterations and associated gene expression changes were identified in etiologically variant pathological HF tissue. The methylation-sensitive and disease-associated genes/ncRNA identified from this study represent a unique cohort of loci that demonstrate a plausible potential as a novel diagnostic and therapeutic target in HF and warrant further investigation.
A Physically Based Climatology of the Occurrence and Intensification of Australian East Coast Lows
Authors: Cavicchia Leone , Pepler Acacia , Dowdy Andrew , Walsh Kevin 
Published: February 2019

AbstractThe subtropical part of the eastern Australian seaboard experiences intense cyclonic activity. The severe damage caused by the intense storms in the region, known as east coast lows (ECLs), has motivated a number of recent studies. Cyclones in this region appear to be driven by a combination of different (barotropic and baroclinic) formation mechanisms, consistent with the view emerging in the last decades that cyclones span a continuous spectrum of dynamical structures, with the barotropically driven tropical cyclone and the baroclinically driven extratropical cyclone being only the extremes of such a spectrum. In this work we revisit the climatology of cyclone occurrence in the subtropical east coast of Australia as seen in a global reanalysis, systematically applying classification criteria based on the cyclone vertical structure and thermal core. Moreover, we investigate the underlying processes driving the cyclone rapid intensification by means of an atmospheric limited-area energetics analysis. We show that ECLs have different spatial patterns according to the cyclone thermal structure, with the fraction of hybrid cyclones being larger toward the tropics and closer to the coast. Moreover, we find that explosively deepening cyclones in this region are driven by a different combination of processes with respect to the global case, with barotropic processes in the surrounding environment having a more dominant role in the energetics of cyclone rapid intensification. The findings of this work contribute to understanding the physical processes underlying the formation and intensification of Australian east coast lows and the associated coastal damage and risk.
Food and physical literacy: Exploring an obesity prevention approach using formative research
Authors: Gibson Isla , Whitelaw Sandy , Topping Christopher , Kopela Joanna 
Published: February 2019

Objective: The objective of this research was to explore how accessible the concept of food and physical literacy is for health and well-being professionals, and assess its potential effect on service delivery. Design: Formative research and ‘concept testing’ with potential deliverers of food and physical literacy. Setting: Dumfries and Galloway, a rural region in South West Scotland, UK. Method: The research was undertaken after four workshops hosted by National Health Service (NHS) public health specialists, aiming to introduce and discuss the concept. An immediate post-event focus group and a short qualitative questionnaire were used to assess professionals’ initial perspectives on the concept, whether they thought the concept was applicable to their work, and what they might require by way of support if the concept was to be taken forward. Results: The findings illustrated the extent to which professionals feel that food and physical literacy is necessary, barriers to its implementation and ideal components for advancing work within this field. Conclusion: The concept of food and physical literacy has a sufficiently high level of resonance (proof of the concept) among informants to provide a foundation on which further work on its operationalisation can be based. The use of formative research and concept testing with potential service deliverers was able to identify areas to be considered during developmental stages, increasing the likelihood that the end result will be accepted by the professionals expected to utilise it. Thus, the benefits of an inclusive approach to service development were also highlighted.
Thiamin deficiency in low- and middle-income countries: Disorders, prevalences, previous interventions and current recommendations
Authors: Johnson Casey R , Fischer Philip R , Thacher Thomas D , Topazian Mark D , Bourassa Megan W , Combs Gerald F 
Published: February 2019

Background: Thiamin deficiency is a major public health concern in several low- and middle-income countries (LMICs)—current attention to the problem is lacking. Aim: This review discusses prevalence of thiamin insufficiency and thiamin-deficiency disorders (TDDs) in LMICs, outlines programmatic experience with thiamin interventions, and offers recommendations to improve public-health and research attention to thiamin in LMICs. Discussion: Thiamin insufficiency, i.e. low-blood-thiamin status, is endemic among several Southeast Asian countries: Cambodia (70–100% of infants and 27–100% of reproductive-age women); Laos (13% of hospitalized infants); Thailand (16–25% of children and 30% of elderly adults). Thiamin deficiency accounts for up to 45% of under-5 deaths in Cambodia, 34% of infant deaths in Laos, and 17% of infant deaths in Myanmar. Deficiency also exists in Africa, Asia, and the Americas, but these instances have typically been isolated. Exclusively breastfed infants of thiamin-deficient mothers are at highest risk for TDD and related death. Intervention strategies that have been employed to combat thiamin deficiency include food processing, fortification, supplementation, dietary diversification, and dietary behaviors, all of which have shown varying levels of effectiveness. Conclusions: We recommend universal thiamin-fortification of context-specific staple-foods in LMICs as a promising solution, as well as thiamin supplementation, particularly for pregnant and lactating women. Food processing regulations, dietary diversification, and modification of dietary behaviors to increase consumption of thiamin-rich foods may provide benefits in some circumstances, especially in countries without universal fortification programs or in populations dependent on food aid.
Differentiation of renal angiomyolipoma without visible fat from renal cell carcinoma by machine learning based on whole-tumor computed tomography texture features
Authors: Cui En-Ming , Lin Fan , Li Qing , Li Rong-Gang , Chen Xiang-Meng , Liu Zhuang-Sheng , Long Wan-Sheng 
Published: February 2019

Background Morphological findings showed poor accuracy in differentiating angiomyolipoma without visible fat (AMLwvf) from renal cell carcinoma (RCC). Purpose To determine the performance of a machine learning classifier in differentiating AMLwvf from different subtypes of RCC based on whole-tumor slices of CT images. Material and Methods In this retrospective study, 171 pathologically proven renal masses were collected from a single institution. Texture features were extracted from whole-tumor images in three phases including the pre-contrast (PCP), corticomedullary (CMP), and nephrographic (NP) phases. A support vector machine with the recursive feature elimination method based on fivefold cross-validation (SVM-RFECV) with the synthetic minority oversampling technique (SMOTE) was utilized to establish classifiers for differentiating AMLwvf from all subtypes of RCC (all-RCC), clear cell RCC (ccRCC), and non-ccRCC. The performances of the classifiers based on three-phase and single-phase images were compared with each other and morphological interpretations. Results A machine learning classifier achieved the best performance in differentiating AMLwvf from all-RCC, ccRCC, and non-ccRCC. The performance of the best machine learning classifier for differentiating AMLwvf from all-RCC (area under the curve [AUC] = 0.96) and ccRCC (AUC = 0.97) was higher than that for differentiating AMLwvf from non-ccRCC (AUC = 0.89); morphological interpretations achieved lower performance for differentiating AMLwvf from all-RCC (AUC = 0.67), ccRCC (AUC = 0.68), and non-ccRCC (AUC = 0.64). Conclusion Machine learning can be a useful non-invasive technique for differentiating AMLwvf from all-RCC, ccRCC, and non-ccRCC, and it can be more accurate than morphological interpretation by radiologists.
Histologic transformation to small-cell lung cancer following gefitinib and radiotherapy in a patient with pulmonary adenocarcinoma
Authors: Fiore Michele , Trecca Pasquale , Perrone Giuseppe , Amato Michelina , Righi Daniela , Trodella Lucio , D’Angelillo Rolando M. , Ramella Sara 
Published: February 2019

Introduction: Targeted therapies against epidermal growth factor receptor (EGFR) have revolutionized the treatment of a subset of lung adenocarcinomas that have EGFR-activating mutations; however, all patients treated with EGFR tyrosine kinase inhibitors (TKIs) ultimately develop resistance. Histologic transformation of EGFR-mutant adenocarcinoma to small cell lung cancer (SCLC) is a resistance mechanism rarely reported in the literature. Case presentation: We describe the case of a woman with metastatic lung cancer adenocarcinoma with mutated EGFR with an initial response to gefitinib and radiation therapy, who progressed after 18 months due to the development of a resistance mechanism. The new biopsy performed after progression highlighted histologic transformation to SCLC, while maintaining the original EGFR mutation. Conclusions: To better identify patients who progress after TKIs and radiation therapy, it is important to perform tumor rebiopsy and collect data to study mechanisms of acquired EGFR TKI resistance.
A rare testicular tumor: primary carcinoid tumor
Authors: Darré Tchin , Doukouré Brahima , Kouyaté Mohamed , Djiwa Toukilnan , Kwamé Doh , Napo-Koura Gado 
Published: February 2019

Background: Primary carcinoid tumors are rare and constitute 0.23% of all testicular tumors. We report a case of primary carcinoid tumor of testicular localization, with a review of the literature. Case presentation: A 29-year-old man, without specific ascendants, consulted the urology department for progressive scrotal swelling of 6 months, associated with pain. After surgery, histology showed diffuse tumor proliferation composed of small round monotone cells with hyperchromatic nuclei evoking undifferentiated carcinoma. Immunohistochemistry showed that tumor cells were positive for chromogranin A and negative for placental alkaline phosphatase and α-fetoprotein. Conclusion: Primary neuroendocrine carcinoma of the testis is a very rare malignant tumor. Immunohistochemistry contributes to its diagnosis in relation to other metastatic neuroendocrine carcinomas, carcinoid tumor teratomas, seminoma, and Sertoli cells.
Differential diagnosis between bone relapse of breast cancer and lambda light chain multiple myeloma: role of the clinical biochemist
Authors: Mastroianni Antonio , Panella Rossella , Morelli Daniele 
Published: February 2019

Purpose: The integration of expertise between oncologist and clinical biochemist for the monitoring and diagnosis of plasma cell dyscrasia is crucial. In some cases, medical laboratory scientists can provide an original contribution using the appropriate techniques to arrive at a diagnosis. Methods: We report a case of 67-year-old woman who was admitted to our hospital for bone pain. Imaging studies showed multiple diffuse bone lytic lesions, and a laboratory screen revealed anemia and altered creatinemia; serum capillary zone electrophoresis confirmed a monoclonal peak in the γ-zone that had been known since 2011, typed as immunoglobulin G kappa by immunosubtraction electrophoresis. The patient had undergone surgery for breast cancer in 2013, and based on her clinical history, the oncologist suspected the presence of bone metastases from the breast cancer and opted for relative therapy. Immunosubtraction, however, showed a very small reduction in lambda free light chains in the beta zone, but it was difficult to establish if was a monoclonal component, and consequently additional tests were performed. Discussion: A monoclonal component composed of only lambda free light chains was evidenced. This result in association with multiple diffuse bone lytic lesions observed led us to suspect multiple myeloma and not bone metastases from the breast cancer. Based on these observations, we encouraged the oncologist to conduct an osteomedullary biopsy, allowing us to make a diagnosis of low-grade stage II lambda light chain multiple myeloma. Conclusion: In this report, we show how the expertise of the clinical biochemist was instrumental in solving this case.
Common feline problem behaviors: Aggression in multi-cat households
Authors: Ramos Daniela 
Published: February 2019

Practical relevance: Being able to understand and intervene in cases of cat–cat aggression in multi-cat households is important for all veterinarians and behavior counsellors dealing with feline behavior cases. Clincal challenges: Feline conflicts are common, perhaps not helped by many owners’ assumption that this is the norm. Interventions can be complex in multi-cat households with large numbers of cats as there are more interactions to evaluate and monitor, and care needs to be taken not to negatively affect the other cats. There may be limitations due to the environment or the people involved and so behavior guidelines should always be tailored to the individual situation. Aims: This article reviews the main forms of aggression in multi-cat households and the appropriate behavioral interventions, considering both the typical scenarios and emotions/motivations most likely involved. It details essential environmental management for multi-cat homes, as well as an approach to friendly cat introductions. Audience: This article is aimed at veterinarians dealing with feline behavior cases as well as behavior counsellors, as both professionals are likely to experience cases of aggression in multi-cat households. Evidence base: The author draws on the published literature where available and, where there is a lack of research, on hypotheses derived from her own clinical behavior experience.
Clostridium difficile colitis in patients undergoing surgery for hip fractures: an analysis of 17,474 patients
Authors: Malik Azeem Tariq , Quatman Carmen E , Phieffer Laura S , Ly Thuan V , Khan Safdar N 
Published: February 2019

Background: We compiled evidence from a large national surgical database to identify the incidence, risk factors and postoperative impact of Clostridium difficile infection (CDI) in patients undergoing hip fracture repair. Methods: We identified 17,474 patients who underwent hip fracture repairs in 2015 using the ACS-NSQIP database. Interventions studied were open reduction/Internal fixation, total hip arthroplasty or hemiarthroplasty being performed for traumatic hip fractures. Outcomes studied were incidence, preoperative and postoperative risk factors for occurrence of CDI were studied using descriptive and statistical analysis. Results: A total of 92 patients (0.53%) developed CDI within 30 days of the operation. Following adjustment using multi-variate logistic regression, preoperative and hospital-associated factors associated with development of CDI were smoking (OR 1.75 [95% CI 1.03–2.99]), hypertension (OR 1.70 [95% CI 1.01–2.85]), hyponatraemia (OR 1.65 [95% CI 1.04–2.63]), prior systemic inflammatory response syndrome (SIRS) (OR 2.18 [95% CI 1.32-3.59]) and a length of stay >7 days (OR 1.98 [95% CI 1.11–3.53]. Postoperative factors associated with occurrence of CDI were occurrence of a deep surgical site infection (SSI) (OR 5.89 [95% CI 1.31–26.6]), a stay in the hospital >30 days (OR 6.56 [95% CI 2.56–16.9]) and unplanned reoperations (OR 2.78 [95% CI 1.29–5.99]). Conclusion: As we move toward an era of bundled-payment models, identification of risk factors associated with the occurrence of postoperative complications, such as CDI, will help curb excess healthcare utilisation and costs associated with the management of this complication.
10-year results of ReCap hip resurfacing arthroplasty: a non-designer case series
Authors: Kiran Manish , Santhapuri Sunil , Moeen Sara , Merchant Irfan , Arvinte Dan , Sood Manoj 
Published: February 2019

Introduction: We present the 10-year results of the ReCap Magnum HRA system in a consecutive single surgeon’s series from a non-designer centre. Patients and methods: Hip resurfacing arthroplasty (HRA) was performed in active males under 65 years and in pre-menopausal females with adequate bone density proven by a DEXA scan. Clinical follow-up; annual Oxford hip scoring, UCLA scoring and whole blood metal ion level measurement. Kaplan-Meier method was used to determine survivorship with revision as the end point. Radiographs were analysed for; acetabular inclination, notching, neck thinning and change in implant position. 72 HRAs were performed in 66 patients with a mean age of 45.7 years. The mean follow-up was 10.63 ± 0.54 years (range 10–11.75 years). Results: The survivorship of the cohort at minimum 10 years was 97.22% (95% confidence interval 94.14–99.01). There was a significant improvement in the Oxford Hip Score from 15.77 ± 4.33 to 45.67 ± 4.43 ( p < 0.001) and the UCLA score from 3.14 ± 0.74 to 7.07 ± 1.16 ( p < 0.001). Mean whole blood cobalt and chromium levels were 28.83 ± 8.42 nmol/l and 39.93 ± 9.64 nmol/l respectively. There were 2 revisions, due to avascular necrosis and implant failure. In our series the implant has performed well with <1% failure per year. We did not note any difference between the genders, since all the females in our series had been screened for osteopenia using a DEXA scan. All our patients returned to an active lifestyle which was maintained at final follow-up. Conclusion: Strict selection criteria and a well-designed implant result in good long-term functional and radiological results with hip resurfacing.
Satisfaction and Awareness of Systemic Psoriasis Treatments: A National Survey Comparing Biologic and Nonbiologic Users
Authors: Ighani Arvin , Yu Ashley M. , Sandhu Vijay K. , Barankin Benjamin , Manolson Morris F. 
Published: February 2019

Background: There is ongoing development of new therapies for psoriasis, including biologic and systemic agents such as interleukin-17, interleukin-23, and phosphodiesterase-4 inhibitors. The development of these agents has changed the landscape of psoriasis treatment options. Objective: The objective of this study was to characterize the impact of newer biologic and systemic agents approved by June 2016 on patient outcomes. We sought to evaluate and compare biologic users and nonbiologic systemic users with respect to their treatment awareness and satisfaction. Methods: We conducted a national Canadian survey from July to September 2016 on adult patients with moderate-to-severe psoriasis using biologic agents or nonbiologic systemic agents as their current primary treatment modality. Patients were asked to evaluate their overall satisfaction with their treatment agent and their awareness of other treatment options. Responses from biologic and nonbiologic systemic users were compared. Results: Overall, 343 participants were included (biologic users: n = 218; nonbiologic users: n = 125). Treatment satisfaction: Biologic users had a higher overall satisfaction score than nonbiologic users ( P < .001). Among nonbiologic agents, apremilast (62%) was associated with the highest satisfaction proportion. Among biologic agents, ustekinumab (77%) and adalimumab (72%) were associated with the highest proportions of satisfaction. With respect to treatment awareness, 30% of nonbiologic patients did not have enough information to form an opinion about biologics. Conclusions: This study demonstrates the greater treatment satisfaction of biologic users compared with nonbiologic users for moderate-to-severe psoriasis. Given that nearly one-third of nonbiologic users did not have enough information to form an opinion about biologic agents, physicians may consider counselling these patients on the use of biologic agents for psoriasis management.
Clinical relevance of cortical network dynamics in early primary progressive MS
Authors: Tur Carmen , Kanber Baris , Eshaghi Arman , Altmann Dan R , Khaleeli Zhaleh , Prados Ferran , Ourselin Sebastian , Thompson Alan J , Gandini Wheeler-Kingshott Claudia AM , Toosy Ahmed T , Ciccarelli Olga 
Published: February 2019

Background: Structural cortical networks (SCNs) reflect the covariance between the cortical thickness of different brain regions, which may share common functions and a common developmental evolution. SCNs appear abnormal in neurodegenerative conditions such as Alzheimer’s and Parkinson’s diseases, but have never been assessed in primary progressive multiple sclerosis (PPMS). Objective: The aim of this study was to test whether SCNs are abnormal in early PPMS and change over 5 years, and correlate with disability worsening. Methods: A total of 29 PPMS patients and 13 healthy controls underwent clinical and brain magnetic resonance imaging (MRI) assessments for 5 years. Baseline and 5-year follow-up cortical thickness values were obtained and used to build correlation matrices, considered as weighted graphs to obtain network metrics. Bootstrap-based statistics assessed SCN differences between patients and controls and between patients with fast and slow progression. Results: At baseline, patients showed features of lower connectivity ( p = 0.02) and efficiency ( p < 0.001) than controls. Over 5 years, patients, especially those with fastest clinical progression, showed significant changes suggesting an increase in network connectivity ( p < 0.001) and efficiency ( p < 0.02), not observed in controls. Conclusion: SCNs are abnormal in early PPMS. Longitudinal SCN changes demonstrated a switch from low- to high-efficiency networks especially among fast progressors, indicating their clinical relevance.