bluuebunny/crossref_metadata_2025_split huggingface dataset:
N6-methyladenosine (m6A) RNA modification in gastrointestinal tract cancers: roles, mechanisms, and applications
Authors: Hu Bin-bin , Wang Xiao-yan , Gu Xu-Yu , Zou Chen , Gao Zhen-jun , Zhang Heng , Fan Yu 
Published: December 2019

AbstractAnalogous to DNA methylation and histone modification, RNA modification, as another epigenetic layer, plays an important role in many diseases, especially in tumours. As the most common form of RNA modification, m6A methylation has attracted increasing research interest in recent years. m6A is catalysed by RNA methyltransferases METTL3, METTL14 and WTAP (writers), m6A is removed by the demethylases FTO and ALKBH5 (erasers) and interacts with m6A-binding proteins, such as YT521-B homology (YTH) domain-containing proteins. This article reviews recent studies on methylation modification of m6A in gastrointestinal tract cancers.
Meningeal inflammation changes the balance of TNF signalling in cortical grey matter in multiple sclerosis
Authors: Magliozzi Roberta , Howell Owain William , Durrenberger Pascal , Aricò Eleonora , James Rachel , Cruciani Carolina , Reeves Cheryl , Roncaroli Federico , Nicholas Richard , Reynolds Richard 
Published: December 2019

Abstract
Background
Recent studies of cortical pathology in secondary progressive multiple sclerosis have shown that a more severe clinical course and the presence of extended subpial grey matter lesions with significant neuronal/glial loss and microglial activation are associated with meningeal inflammation, including the presence of lymphoid-like structures in the subarachnoid space in a proportion of cases.

Methods
To investigate the molecular consequences of pro-inflammatory and cytotoxic molecules diffusing from the meninges into the underlying grey matter, we carried out gene expression profiling analysis of the motor cortex from 20 post-mortem multiple sclerosis brains with and without substantial meningeal inflammation and 10 non-neurological controls.

Results
Gene expression profiling of grey matter lesions and normal appearing grey matter not only confirmed the substantial pathological cell changes, which were greatest in multiple sclerosis cases with increased meningeal inflammation, but also demonstrated the upregulation of multiple genes/pathways associated with the inflammatory response. In particular, genes involved in tumour necrosis factor (TNF) signalling were significantly deregulated in MS cases compared with controls. Increased meningeal inflammation was found to be associated with a shift in the balance of TNF signalling away from TNFR1/TNFR2 and NFkB-mediated anti-apoptotic pathways towards TNFR1- and RIPK3-mediated pro-apoptotic/pro-necroptotic signalling in the grey matter, which was confirmed by RT-PCR analysis. TNFR1 was found expressed preferentially on neurons and oligodendrocytes in MS cortical grey matter, whereas TNFR2 was predominantly expressed by astrocytes and microglia.

Conclusions
We suggest that the inflammatory milieu generated in the subarachnoid space of the multiple sclerosis meninges by infiltrating immune cells leads to increased demyelinating and neurodegenerative pathology in the underlying grey matter due to changes in the balance of TNF signalling.
Potential treatment effect modifiers for manipulative therapy for children complaining of spinal pain.Secondary analyses of a randomised controlled trial
Authors: Dissing Kristina Boe , Vach Werner , Hartvigsen Jan , Wedderkopp Niels , Hestbæk Lise 
Published: December 2019

Abstract
Background
In children, spinal pain is transitory for most, but up to 20% experience recurrent and bothersome complaints. It is generally acknowledged that interventions may be more effective for subgroups of those affected with low back pain. In this secondary analysis of data from a randomized clinical trial, we tested whether five indicators of a potential increased need for treatment might act as effect modifiers for manipulative therapy in the treatment of spinal pain in children. We hypothesized that the most severely affected children would benefit more from manipulative therapy.

Method
This study was a secondary analysis of data from a randomised controlled trial comparing advice, exercises and soft tissue treatment with and without the addition of manipulative therapy in 238 Danish school children aged 9–15 years complaining of spinal pain. A text message system (SMS) and clinical examinations were used for data collection (February 2012 to April 2014).
Five pre-specified potential effect modifiers were explored: Number of weeks with spinal pain 6 months prior to inclusion, number of weeks with co-occurring musculoskeletal pain 6 months prior to inclusion, expectations of the clinical course, pain intensity, and quality of life.
Outcomes were number of recurrences of spinal pain, number of weeks with pain, length of episodes, global perceived effect, and change in pain intensity. To explore potential effect modification, various types of regression models were used depending on the type of outcome, including interaction tests.

Results
We found that children with long duration of spinal pain or co-occurring musculoskeletal pain prior to inclusion as well as low quality of life at baseline tended to benefit from manipulative therapy over non-manipulative therapy, whereas the opposite was seen for children reporting high intensity of pain. However, most results were statistically insignificant.

Conclusions
This secondary analysis indicates that children more effected by certain baseline characteristics, but not pain intensity, have a greater chance to benefit from treatment that include manipulative therapy. However, these analyses were both secondary and underpowered, and therefore merely exploratory. The results underline the need for a careful choice of inclusion criteria in future investigations of manipulative therapy in children.

Trial registration
NCT01504698; results
Socioeconomic factors and lifestyles influencing the incidence of calcaneal fractures, a national population-based survey in China
Authors: Zhu Yanbin , Li Jia , Liu Song , Chen Wei , Wang Lin , Zhang Xiaolin , Zhang Yingze 
Published: December 2019

Abstract
Background
We aimed to do a national survey on the population-based incidence of calcaneal fracture in China.

Methods
All the data on calcaneal fractures were available from the China National Fracture Survey (CNFS) between January and May in 2015. And in the CNFS, all eligible household members were sampled from 8 provinces, 24 urban cities and 24 rural counties in China, using stratified random sampling and the probability proportional to size method. Questionnaires were sent to every participant for data collection and quality control was accomplished by our research team members.

Results
A total of 512187 valid questionnaires were collected and relevant data were abstracted and analyzed. There were 59 patients with 62 calcaneal fractures occurring in 2014, indicating that the incidence was 11.5/100,000 person-years, 17.3/100,000 in males, and 5.5/100,000 in females. BMI ≥ 28.0 kg/m2, scarce meat consumption, smoking, alcohol consumption, average sleep time < 7 h/day, and previous history of fracture were identified as independent risk factors for calcaneal fracture.

Conclusions
Specific public health policies focusing on quitting smoking, decreasing alcohol consumption, and encouraging individuals to obtain sufficient sleep should be implemented. Reasonable meat consumption and maintaining a normal body weight should be emphasized in individuals, especially in those with previous fracture.
Associations of foot ulceration with quality of life and psychosocial determinants among patients with diabetes; a case‐control study
Authors: Alosaimi Fahad D. , Labani Reem , Almasoud Nouf , Alhelali Nora , Althawadi Lamya , AlJahani Dhaherah Mani 
Published: December 2019

AbstractBackgroundPatients with diabetic foot ulcers may have a lower quality of life. The objective was to compare the quality of life and its psychosocial determinants among patients with and without diabetic foot ulcers.MethodsA case‐control study was conducted in 2017 among patients with (cases) and without (controls) diabetic foot ulcers. The study tools included the World Health Organization's Quality of Life scale (WHOQOL‐BREF), the Hospital Anxiety and Depression (HAD) scale for anxiety and depression, the Patient Health Questionnaire Physical Symptoms (PHQ‐15) for the severity of somatic symptoms, and the Summary of Diabetes Self‐Care Activities (SDSCA) measure for self‐management.ResultsA total of 209 patients (45 cases and 164 controls) were included. The average age was 56.2 ± 11.7 years, and 55.5% were female. The average scores of WHOQOL‐BREF, PHQ‐15, and SDSCA were 74.4% ± 12.1% and 8.1 ± 6.1, and 30.4 ± 21.8, respectively. The prevalence of anxiety and depression were 19.6 and 24.9%, respectively. SDSCA was the only psychosocial determinants higher in cases than controls (mean difference = 15.0, 95% CI = ‐8.0–22.0). The correlation coefficients of WHOQOL‐BREF scores with anxiety, depression, and PHQ‐15 scores in all patients were − 0.559 (p < 0.001), − 0.582 (p < 0.001), and − 0.532 (p < 0.001), respectively, with similar numbers in both groups. In multivariate analysis, only the association between quality of life and depression was maintained.ConclusionQuality of life and psychosocial determinants with the exception of self‐management were not associated with diabetic foot ulcers. Depressive symptoms were independent determinant of poor quality of life, irrespective of the status of diabetic foot ulcers.
PET and CSF amyloid-β status are differently predicted by patient features: information from discordant cases
Authors: Reimand Juhan , de Wilde Arno , Teunissen Charlotte E. , Zwan Marissa , Windhorst Albert D. , Boellaard Ronald , Barkhof Frederik , van der Flier Wiesje M. , Scheltens Philip , van Berckel Bart N. M. , Ossenkoppele Rik , Bouwman Femke 
Published: December 2019

AbstractBackgroundAmyloid-β PET and CSF Aβ42yield discordant results in 10–20% of memory clinic patients, possibly providing unique information. Although the predictive power of demographic, clinical, genetic, and imaging features for amyloid positivity has previously been investigated, it is unknown whether these features differentially predict amyloid-β status based on PET or CSF or whether this differs by disease stage.MethodsWe included 768 patients (subjective cognitive decline (SCD,n = 194), mild cognitive impairment (MCI,n = 127), dementia (AD and non-AD,n = 447) with amyloid-β PET and CSF Aβ42measurement within 1 year. Ninety-seven (13%) patients had discordant PET/CSF amyloid-β status. We performed parallel random forest models predicting separately PET and CSF status using 17 patient features (demographics, APOE4 positivity, CSF (p)tau, cognitive performance, and MRI visual ratings) in the total patient group and stratified by syndrome diagnosis. Thereafter, we selected features with the highest variable importance measure (VIM) as input for logistic regression models, where amyloid status on either PET or CSF was predicted by (i) the selected patient feature and (ii) the patient feature adjusted for the status of the other amyloid modality.ResultsAPOE4, CSF tau, and p-tau had the highest VIM for PET and CSF in all groups. In the amyloid-adjusted logistic regression models, p-tau was a significant predictor for PET-amyloid in SCD (OR = 1.02 [1.01–1.04],pFDR = 0.03), MCI (OR = 1.05 [1.02–1.07],pFDR < 0.01), and dementia (OR = 1.04 [1.03–1.05],pFDR < 0.001), but not for CSF-amyloid. APOE4 (OR = 3.07 [1.33–7.07],punc < 0.01) was associated with CSF-amyloid in SCD, while it was only predictive for PET-amyloid in MCI (OR = 9.44 [2.93, 30.39],pFDR < 0.01). Worse MMSE scores (OR = 1.21 [1.03–1.41],punc = 0.02) were associated to CSF-amyloid status in SCD, whereas worse memory (OR = 1.17 [1.05–1.31],pFDR = 0.02) only predicted PET positivity in dementia.ConclusionAmyloid status based on either PET or CSF was predicted by different patient features, and this varied by disease stage, suggesting that PET-CSF discordance yields unique information. The stronger associations of both APOE4 carriership and worse memory z-scores with CSF-amyloid in SCD suggest that CSF-amyloid is more sensitive early in the disease course. The higher predictive value of CSF p-tau for a positive PET scan suggests that PET is more specific to AD pathology.
Scrub typhus with multi-organ dysfunction syndrome and immune thrombocytopenia: a case report and review of the literature
Authors: Li Weijia , Huang Lei , Zhang Weixing 
Published: December 2019

Abstract
Background
Scrub typhus is an acute infectious zoonotic disease caused by Orientia tsutsugamushi. Multi-organ dysfunction secondary to scrub typhus is hard to diagnose and has a high mortality rate. Only one case of scrub typhus with multi-organ dysfunction syndrome and immune thrombocytopenia has been reported thus far. In this study, we report a second case of scrub typhus with multi-organ dysfunction syndrome and immune thrombocytopenia, and we summarize its diagnosis and treatment.

Case presentation
A 43-year-old Han Chinese woman, a sanitation worker, was admitted to our hospital after 7 days of a skin infection and 5 days of a sore throat with fever and dizziness. A physical examination revealed the presence of an eschar on the right side of her neck. She had a history of insect bites during her sanitation work. A diagnostic evaluation identified scrub typhus as the primary illness, which was associated with multi-organ dysfunction syndrome and immune thrombocytopenia. She recovered completely after 15 days of treatment and extensive symptomatic supportive care.

Conclusion
We report a second case of tsutsugamushi disease with multi-organ dysfunction syndrome and immune thrombocytopenia, which resolved after treatment and extensive care.
SUV variability in EARL-accredited conventional and digital PET
Authors: Koopman Daniëlle , Jager Pieter L. , Slump Cornelis H. , Knollema Siert , van Dalen Jorn A. 
Published: December 2019

Abstract
Background
A high SUV-reproducibility is crucial when different PET scanners are in use. We evaluated the SUV variability in whole-body FDG-PET scans of patients with suspected or proven cancer using an EARL-accredited conventional and digital PET scanner.
In a head-to-head comparison we studied images of 50 patients acquired on a conventional scanner (cPET, Ingenuity TF PET/CT, Philips) and compared them with images acquired on a digital scanner (dPET, Vereos PET/CT, Philips). The PET scanning order was randomised and EARL-compatible reconstructions were applied.
We measured SUVmean, SUVpeak, SUVmax and lesion diameter in up to 5 FDG-positive lesions per patient. The relative difference ΔSUV between cPET and dPET was calculated for each SUV-parameter. Furthermore, we calculated repeatability coefficients, reflecting the 95% confidence interval of ΔSUV.

Results
We included 128 lesions with an average size of 19 ± 14 mm. Average ΔSUVs were 6-8% with dPET values being higher for all three SUV-parameters (p < 0.001). ΔSUVmax was significantly higher than ΔSUVmean (8% vs. 6%, p = 0.002) and than ΔSUVpeak (8% vs. 7%, p = 0.03). Repeatability coefficients across individual lesions were 27% (ΔSUVmean and ΔSUVpeak) and 33% (ΔSUVmax) (p < 0.001).

Conclusions
With EARL-accredited conventional and digital PET, we found a limited SUV variability with average differences up to 8%. Furthermore, only a limited number of lesions showed a SUV difference of more than 30%. These findings indicate that EARL standardisation works.

Trial registration
This prospective study was registered on the 31th of October 2017 at ClinicalTrials.cov. URL: https://clinicaltrials.gov/ct2/show/NCT03457506?id=03457506&rank=1.
Kleeblattschädel skull presenting in concert with Pfeiffer syndrome
Authors: Sajid Mir Ibrahim , Malik Noor , Balouch Samira S. , Javed Gohar 
Published: December 2019

Abstract
Background
Kleeblattschädel skull, also known as the cloverleaf is a complex synostosis which presents with an enlarged tri-lobar skull resulting temporal bulging and a flat posterior skull, a rare find in the population. This pansynostosis is associated with other congenital syndromes which include Crouzon, Pfeifer, and Carpenter’s. The genetic disorder Pfeiffer syndrome results from skull bones’ premature fusion characterized by deformities of the hand and feet. The author reports a 10-month-old girl who presented with a tri-lobar skull and wide toes which is a significant finding of Pfeiffer syndrome.

Case presentation
A 10-month-old girl presents with congenital obstructive hydrocephalus due to cloverleaf skull with horizontally enlarged head and large fontanelles. The child also had mid-facial hypoplasia and pre-axial bilateral lower limb polydactyly. Wide toes were also observed, an indicator of Pfeiffer’s Syndrome. Computed tomography (CAT) scans grossly abnormal craniofacial appearances, with premature closure of the sagittal suture giving a cloverleaf skull appearance. There was also a significant thinning of the brain parenchyma.

Conclusion
Premature closure of sutures leads to a forced growth in a plane perpendicular to the closed suture. Cloverleaf deformity can present with multiple syndromes such as Pfeiffer’s. This leads to gross alteration of the skull with potential underlying morbidity.
Pulmonary arterial hypertension: the case for a bioelectronic treatment
Authors: Ntiloudi Despοina , Qanud Khaled , Tomaio Jacquelyn-Nicole , Giannakoulas George , Al-Abed Yousef , Zanos Stavros 
Published: December 2019

AbstractPulmonary arterial hypertension (PAH) is a rare disease of unknown etiology that progresses to right ventricular failure. It has a complex pathophysiology, which involves an imbalance between vasoconstrictive and vasodilative processes in the pulmonary circulation, pulmonary vasoconstriction, vascular and right ventricular remodeling, systemic inflammation, and autonomic imbalance, with a reduced parasympathetic and increased sympathetic tone. Current pharmacological treatments for PAH include several classes of drugs that target signaling pathways in vascular biology and cardiovascular physiology, but they can have severe unwanted effects and they do not typically stop the progression of the disease. Pulmonary artery denervation has been tested clinically as a method to suppress sympathetic overactivation, however it is a nonspecific and irreversible intervention. Bioelectronic medicine, in particular vagus nerve stimulation (VNS), has been used in cardiovascular disorders like arrhythmias, heart failure and arterial hypertension and could, in principle, be tested as a treatment in PAH. VNS can produce pulmonary vasodilation and renormalize right ventricular function, via activation of pulmonary and cardiac vagal fibers. It can suppress systemic inflammation, via activation of fibers that innervate the spleen. Finally, VNS can gradually restore the balance between parasympathetic and sympathetic tone by regulating autonomic reflexes. Preclinical studies support the feasibility of using VNS in PAH. However, there are challenges with such an approach, arising from the need to affect a relatively small number of relevant vagal fibers, and the potential for unwanted cardiac and noncardiac effects of VNS in this sensitive patient population.
Plasminogen activator inhibitor (PAI-1) gene polymorphism (4G/5G) and hepatocellular carcinoma in Egyptian patients
Authors: Nemr Nader , Mandour Mohamed , Badran Dahlia , Kishk Rania , Attia Fawzy , Hashish Abdullah , Gaber Ahmed 
Published: December 2019

Abstract
Background
Plasminogen activator inhibitor-1 (PAI-1), which is a part of urokinase plasminogen activation (uPA) system, had been reported to have a crucial role in the development of different types of cancers. The PAI-1 gene, located on chromosome 7, contains nine exons and eight introns. This gene is highly polymorphic, and its most common polymorphism (4G/5G) affects PAI-1 biosynthesis and consequently its circulating level.

Aim
The current study investigated the distribution of genotypes and the allelic frequency of the PAI-1 4G/5G polymorphism in hepatocellular carcinoma (HCC) compared to chronic HCV patients living in Egypt. Additionally, the effect of the PAI-1 4G/5G polymorphism on serum PAI-1 levels was assessed.

Methods
The study was carried on 50 HCC and 47 chronic HCV patients using real-time polymerase chain reaction.

Results
The genotypic distributions of the 4G/5G polymorphism (5G/5G, 4G/4G, 4G/5G, and 4G/4G + 4G/5G) and the frequency of alleles (5G and 4G) were not statistically significantly different between both study groups (p > 0.05). In addition, serum levels of PAI-1did not show any significant difference between HCC patients and HCV patients regarding all different genotypes of the 5G/4G polymorphism at p > 0.05 neither between the different genotypes of the 5G/4G polymorphism in the same group at p > 0.05.

Conclusion
Our study suggests that the PAI-1 4G/5G polymorphism may not be considered as one of the underlying genetic causes of hepatocarcinogenesis in chronically HCV-infected patients living in Egypt.
Prolactin Enhances the Proliferation of Proliferative Endometrial Glandular Cells and Endometrial Cancer Cells
Authors: Yamaguchi Munekage , Erdenebaatar Chimeddulam , Saito Fumitaka , Honda Ritsuo , Ohba Takashi , Kyo Satoru , Tashiro Hironori , Katabuchi Hidetaka 
Published: December 2019

Abstract
To elucidate the mechanism of endometrial cancer (EC) development in young hyperprolactinemic women, this study assessed the hormonal receptor expression, proliferation, and signaling induced by prolactin in endometrial glands (EG) and EC.
Prolactin receptor (PRLR) and estrogen receptor alpha (ER-α) in EG were evaluated during the menstrual cycle by immunohistochemistry. The following parameters were compared between EM-E6/E7/TERT cells, which originated from proliferative EG and Ishikawa cells. The expression levels of PRLR, pJAK2 (phosphorylated Janus Activating Kinase 2), its downstream pathways (MAPK, PI3K, and STAT), and ER-α were assessed after adding prolactin by Western blotting. U0126 was used as a MAPK inhibitor. The proliferation caused by estradiol was also examined by MTS assay after adding prolactin.
PRLR expression in the EG was significantly higher in the proliferative phase than in the secretory phase, and it was correlated with ER-α expression during the menstrual cycle. After adding prolactin, the expression of pJAK2, PRLR and ER-α was significantly increased in both cell lines, MAPK was activated after adding prolactin in both cell lines, and PI3K and STAT were activated only in EM-E6/E7/TERT cells. The increased proliferation induced by estradiol was enhanced after adding prolactin in both cell lines. All changes caused by prolactin were inhibited in Ishikawa cells pretreated with U0126.
Long-term effects of serum prolactin on persistent proliferative endometrium in the presence of estradiol may induce abnormal proliferation of EG in hyperprolactinemic women. Prolactin-PRLR signaling via MAPK may play a crucial role in the progression of EC in hyperprolactinemic women.