bluuebunny/crossref_metadata_2025 huggingface dataset:
Prosecuting controlling or coercive behaviour in England and Wales: Media reports of a novel offence
Authors: McGorrery Paul , McMahon Marilyn
Published: October 2019

The offence of controlling or coercive behaviour came into effect in England and Wales in December 2015, and related offences have since been enacted in Scotland and Ireland. To date, there has been almost no empirical evaluation of the operationalisation of the new English and Welsh offence. This article fills that gap by analysing media reports relating to 107 individuals convicted of controlling or coercive behaviour, providing a profile of offenders and victims (gender and age), the types of abusive behaviours offenders engaged in and how the cases progressed through the criminal justice system (manner of conviction, sentencing outcomes). Media reporting of these cases is also discussed. The results suggest that the offence is (appropriately) operationalised in a highly gendered manner, that it has captured a diverse range of behaviours that would not previously have been considered criminal, and that media reports of this form of domestic violence have not demonstrated the negativity towards victims identified in previous studies. Further research of primary data is required to confirm these findings.
2D in-vivo L-COSY spectroscopy identifies neurometabolite alterations in treated multiple sclerosis
Authors: Quadrelli Scott , Ribbons Karen , Arm Jameen , Al-iedani Oun , Lechner-Scott Jeannette , Lea Rodney , Ramadan Saadallah
Published: October 2019

Background:

We have applied in vivo two-dimensional (2D) localized correlation spectroscopy (2D L-COSY), in treated relapsing relapsing-remitting multiple sclerosis (RRMS) to identify novel biomarkers in normal-appearing brain parenchyma.

Methods:

2D L-COSY magnetic resonance spectroscopy (MRS) spectra were prospectively acquired from the posterior cingulate cortex (PCC) in 45 stable RRMS patients undergoing treatment with Fingolimod, and 40 age and sex-matched healthy control (HC) participants. Average metabolite ratios and clinical symptoms including, disability, cognition, fatigue, and mental health parameters were measured, and compared using parametric and nonparametric tests. Whole brain volume and MRS voxel morphometry were evaluated using SIENAX and the SPM LST toolbox.

Results:

Despite the mean whole brain lesion volume being low in this RRMS group (6.8 ml) a significant reduction in PCC metabolite to tCr ratios were identified for multiple N-acetylaspartate (NAA) signatures, gamma-aminobutyric acid (GABA), glutamine and glutamate (Glx), threonine, and isoleucine/lipid. Of the clinical symptoms measured, visuospatial function, attention, and memory were correlated with NAA signatures, Glx, and isoleucine/lipid in the brain.

Conclusions:

2D L-COSY has the potential to detect metabolic alterations in the normal-appearing MS brain. Despite examining only a localised region, we could detect metabolic variability associated with symptoms.
Primary oral manifestation of Langerhans cell histiocytosis refractory to conventional therapy but susceptible to BRAF-specific treatment: a case report and review of the literature
Authors: Neckel Norbert , Lissat Andrej , von Stackelberg Arendt , Thieme Nadine , Doueiri Mohemed-Salim , Spors Birgit , Beck-Broichsitter Benedicta , Heiland Max , Raguse Jan-Dirk
Published: October 2019

Langerhans cell histiocytosis (LCH) is a diagnostic and therapeutic challenge. We report on a rare case of its primary oral manifestation that was treated successfully with the BRAF-specific agent, vemurafenib, after insufficient standard LCH treatment. This case underlines the importance of proper diagnosis and the evaluation of targeted therapy as a valuable tool in LCH treatment. Furthermore, the close collaboration of surgeons, oncologists, and dentists is mandatory to ensure adequate treatment, restore the stomatognathic system in debilitating post-treatment situations, improve quality of life, and ensure effective disease control in infants and young patients.
Testing a model of subjective well-being: The roles of optimism, psychological vulnerability, and shyness
Authors: Satici Begum
Published: October 2019

This research extended current positive psychological research by investigating the mediating effect of shyness on the association between optimism, psychological vulnerability and subjective well-being. Two hundred fifty-five volunteer university students (131 females and 124 males, mean age = 23.14) participated in the study. The structural equation modeling revealed shyness fully mediated the effect of psychological vulnerability on subjective well-being, while shyness partially mediated the effect of optimism on subjective well-being. Also, bootstrapping procedures confirmed that psychological vulnerability was indirectly associated with subjective well-being through shyness, whereas optimism was directly associated with subjective well-being. The implications for future studies and the limitations of the study were discussed in the context of the relevant literature.
Respiratory muscle activity after spontaneous, neostigmine- or sugammadex-enhanced recovery of neuromuscular blockade: a double blind prospective randomized controlled trial
Authors: Schepens Tom , Janssens Koen , Maes Sabine , Wildemeersch Davina , Vellinga Jurryt , Jorens Philippe G. , Saldien Vera
Published: October 2019

Background

The use of neostigmine after neuromuscular blockade (NMB) has been associated with postoperative respiratory complications. In previous studies, we found lower diaphragmatic activity after neostigmine reversal of NMB, compared to sugammadex. It is still unclear whether the adequate use of neostigmine guarantees normal respiratory muscle function after NMB. In this study, we wanted to assess the effect of commonly used degrees of NMB and their possible reversal strategies on respiratory muscle activity after the return of normal neuromuscular transmission.

Methods

This is a randomized, controlled, parallel-group, single-centre, double-blind study in patients scheduled for intracranial surgery at a tertiary academic hospital in Belgium. All participants received target controlled propofol/remifentanil anesthesia and were randomized into one of five groups, receiving either a shallow NMB with no reversal (shallow/saline), a shallow NMB with sugammadex reversal (shallow/sugammadex), a moderate NMB with neostigmine reversal (moderate/neostigmine), a moderate NMB with sugammadex reversal (moderate/sugammadex), or a deep NMB with sugammadex reversal (deep/sugammadex). Primary and secondary outcome parameters were diaphragm and intercostal electromyographic (EMG) activity at the moment of resumed spontaneous breathing activity, defined as a maximal interval of 10 min after the first spontaneous breath.

Results

For the five groups, a total of 55 patients could be included in the final analysis. Median time of spontaneous breathing analyzed was 5 min (IQR 3–9.5 min). Both the moderate/sugammadex and the moderate/neostigmine groups had lower levels of diaphragm EMG compared to the shallow/sugammadex group. The moderate/neostigmine group had lower levels of intercostal EMG activity compared to the shallow/saline group.

Conclusions

In this study, the depth of neuromuscular blockade and type of reversal strategy impacts respiratory muscle activity at the moment of resumed spontaneous breathing and recovery of neuromuscular blockade. Both groups that received moderate NMB had lower levels of diaphragm EMG, compared to the shallow NMB group with sugammadex reversal. Compared to the shallow NMB group with no reversal, the moderate NMB with neostigmine reversal group had lower intercostal EMG activity.

Trial registration

Clinicaltrials.gov NCT01962298 on October 9, 2013 and EudraCT 2013–001926-25 on October 10, 2013.
Comparative assessment and monitoring of deterioration of articulatory organs using subjective and objective tools among patients with amyotrophic lateral sclerosis
Authors: Pawlukowska Wioletta , Baumert Bartłomiej , Gołąb-Janowska Monika , Meller Agnieszka , Machowska-Sempruch Karolina , Wełnicka Agnieszka , Paczkowska Edyta , Rotter Iwona , Machaliński Bogusław , Nowacki Przemysław
Published: October 2019

Background

Amyotrophic lateral sclerosis (ALS) is a fatal degenerative disease of a rapid course. In 25% of ALS sufferers, speech disorders occur as prodromal symptoms of the disease. Impaired communication affects physical health and has a negative impact on mental and emotional condition. In this study, we assessed which domains of speech are particularly affected in ALS. Subsequently, we estimated possible correlations between the ALS patients’ subjective perception of their speech quality and an objective assessment of the speech organs carried out by an expert.

Methods

The study group consisted of 63 patients with sporadic ALS. The patients were examined for articulatory functions by means of Voice Handicap Index (VHI) and the Frenchay Dysarthria Assessment (FDA).

Results

On the basis of the VHI scores, the entire cohort was divided into 2 groups: group I (40 subjects) with mild speech impairment, and group II (23 subjects) displaying moderate and profound speech deficits. In an early phase of ALS, changes were typically reported in the tongue, lips and soft palate. The FDA and VHI-based measurements revealed a high, positive correlation between the objective and subjective evaluation of articulation quality.

Conclusions

Deterioration of the articulatory organs resulted in the reduction of social, physical and emotional functioning. The highly positive correlation between the VHI and FDA scales seems to indicate that the VHI questionnaire may be a reliable, self-contained tool for monitoring the course and progression of speech disorders in ALS.

Trial registration

NCT02193893.
Tumor-associated macrophages: an accomplice in solid tumor progression
Authors: Chen Yibing , Song Yucen , Du Wei , Gong Longlong , Chang Haocai , Zou Zhengzhi
Published: October 2019

In many solid tumor types, tumor-associated macrophages (TAMs) are important components of the tumor microenvironment (TME). Moreover, TAMs infiltration is strongly associated with poor survival in solid tumor patients. In this review, we describe the origins of TAMs and their polarization state dictated by the TME. We also specifically focus on the role of TAMs in promoting tumor growth, enhancing cancer cells resistance to chemotherapy and radiotherapy, promoting tumor angiogenesis, inducing tumor migration and invasion and metastasis, activating immunosuppression. In addition, we discuss TAMs can be used as therapeutic targets of solid tumor in clinics. The therapeutic strategies include clearing macrophages and inhibiting the activation of TAMs, promoting macrophage phagocytic activity, limiting monocyte recruitment and other targeted TAMs therapies.
M2e-based universal influenza vaccines: a historical overview and new approaches to development
Authors: Mezhenskaya Daria , Isakova-Sivak Irina , Rudenko Larisa
Published: October 2019

The influenza A virus was isolated for the first time in 1931, and the first attempts to develop a vaccine against the virus began soon afterwards. In addition to causing seasonal epidemics, influenza viruses can cause pandemics at random intervals, which are very hard to predict. Vaccination is the most effective way of preventing the spread of influenza infection. However, seasonal vaccination is ineffective against pandemic influenza viruses because of antigenic differences, and it takes approximately six months from isolation of a new virus to develop an effective vaccine. One of the possible ways to fight the emergence of pandemics may be by using a new type of vaccine, with a long and broad spectrum of action. The extracellular domain of the M2 protein (M2e) of influenza A virus is a conservative region, and an attractive target for a universal influenza vaccine. This review gives a historical overview of the study of M2 protein, and summarizes the latest developments in the preparation of M2e-based universal influenza vaccines.
Relationships of coronary culprit-plaque characteristics with duration of diabetes mellitus in acute myocardial infarction: an intravascular optical coherence tomography study
Authors: Sheng Zhaoxue , Zhou Peng , Liu Chen , Li Jiannan , Chen Runzhen , Zhou Jinying , Song Li , Zhao Hanjun , Yan Hongbing
Published: October 2019

Background

Diabetes mellitus (DM) or pre-diabetes status is closely associated with features of vulnerable coronary lesions in patients with stable coronary heart disease or acute coronary syndrome. However, the association between duration of diabetes and the morphologies and features of vulnerable plaques has not been fully investigated in patients with acute myocardial infarction (AMI).

Methods

We enrolled a total of 279 patients who presented with AMI between March 2017 and March 2019 and underwent pre-intervention optical coherence tomography imaging of culprit lesions. Patients with DM were divided into two subgroups: a Short-DM group with DM duration of < 10 years and a Long-DM group with DM duration of ≥ 10 years. Baseline clinical data and culprit-plaque characteristics were compared between patients without DM (the non-DM group), those in the Short-DM group, and those in the Long-DM group.

Results

Patients with DM represented 34.1% of the study population (95 patients). The Short- and Long-DM groups included 64 (67.4%) and 31 patients (32.6%), respectively. Glycated hemoglobin A1c (HbA1c) levels were significantly higher in the Long-DM group than the Non- or Short-DM groups (8.4% [Long-DM] versus 5.7% [Non-DM] and 7.6% [Short-DM], P < 0.001). In addition, the highest prevalence of lipid-rich plaques, thin-cap fibroatheroma (TCFA), and plaque ruptures of culprit lesions were observed in the Long-DM group (lipid-rich plaques: 80.6% [Long-DM] versus 52.2% [Non-DM] and 62.5% [Short-DM], P = 0.007; TCFA: 41.9% [Long-DM] versus 19.6% [Non-DM] and 31.3% [Short-DM], P = 0.012; plaque rupture: 74.2% [Long-DM] versus 46.7% [Non-DM] and 48.4% [Short-DM], P = 0.017). The frequency of calcification was significantly higher among patients with DM than among those without (62.1% versus 46.2%, P = 0.016); however, no significant differences were found between the DM subgroups (61.3% [Long-DM] versus 62.5% [Short-DM], P = 0.999).

Conclusions

Increased duration of DM combined with higher HbA1c levels influences culprit-plaque characteristics in patients with DM who suffer AMI. These findings might account for the higher risks of cardiac death in DM patients with long disease duration.

Trial registration This study is registered at clinicaltrials.gov as NCT03593928
DALBACEN cohort: dalbavancin as consolidation therapy in patients with endocarditis and/or bloodstream infection produced by gram-positive cocci
Authors: Hidalgo-Tenorio Carmen , Vinuesa David , Plata Antonio , Martin Dávila Pilar , Iftimie Simona , Sequera Sergio , Loeches Belén , Lopez-Cortés Luis Eduardo , Fariñas Mari Carmen , Fernández-Roldan Concepción , Javier-Martinez Rosario , Muñoz Patricia , Arenas-Miras Maria del Mar , Martínez-Marcos Francisco Javier , Miró Jose Maria , Herrero Carmen , Bereciartua Elena , De Jesus Samantha E. , Pasquau Juan
Published: October 2019

Objectives

To analyse the effectiveness of dalbavancin (DBV) in clinical practice as consolidation therapy in patients with bloodstream infection (BSI) and/or infective endocarditis (IE) produced by gram-positive cocci (GPC), as well as its safety and pharmacoeconomic impact.

Methods

A multicentre, observational and retrospective study was conducted of hospitalised patients with IE and/or BSI produced by GPC who received at least one dose of DBV. Clinical response was assessed during hospitalization, at 3 months and at 1 year.

Results

Eighty-three patients with median age of 73 years were enrolled; 73.5% were male; 59.04% had BSI and 49.04% IE (44.04% prosthetic valve IE, 32.4% native IE, 23.5% pacemaker lead). The most frequently isolated microorganism wasStaphylococcus aureusin BSI (49%) and coagulase-negative staphylococci in IE (44.1%). All patients with IE were clinically cured in hospital; at 12 months, there was 2.9% loss to follow-up, 8.8% mortality unrelated to IE, and 2.9% therapeutic failure rate. The percentage effectiveness of DBV to treat IE was 96.7%. The clinical cure rate for BSI was 100% during hospital stay and at 3 months; there were no recurrences or deaths during the follow-up. No patient discontinued treatment for adverse events. The saving in hospital stay was 636 days for BSI (315,424.20€) and 557 days for IE (283,187.45€).

Conclusions

DBV is an effective consolidation antibiotic therapy in clinically stabilized patients with IE and/or BSI. It proved to be a cost-effective treatment, reducing the hospital stay, thanks to the pharmacokinetic/pharmacodynamic profile of this drug.
Effects of FSHR polymorphisms on premature ovarian insufficiency in human beings: a meta-analysis
Authors: Huang Wenling , Cao Ying , Shi Lei
Published: October 2019

Background

Whether follicle-stimulating hormone receptor (FSHR) polymorphisms are implicated in premature ovarian insufficiency (POI) remains controversial. Thus, we performed this study to explore correlation between FSHR polymorphisms and POI in human beings.

Methods

Literature retrieve was conducted in PubMed, Medline, Embase and CNKI. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated.

Results

Sixteen studies were enrolled for analyses. No significant relationship with POI was found for rs6165 and rs6166 polymorphisms in overall analyses. Further subgroup analyses revealed that rs6166 polymorphism was significantly associated with the risk of POI in Asians with both FEM and REM. Nevertheless, we failed to detect any significant associations with POI for other ethnicities.

Conclusions

Our findings indicated that FSHR rs6166 polymorphism may serve as a potential genetic biomarker of POI in Asians, but not in other ethnicities.
Intercellular adhesion molecule-1 expression and serum levels as markers of pre-clinical atherosclerosis in polycystic ovary syndrome
Authors: Rashad Nearmeen M. , El-Shal Amal S. , Abomandour Hala G. , Aboelfath Amr Mostafa Kamel , Rafeek Mohamed el sayed , Badr Mohammad Samir , Ali Ayman E. , Yousef Mohammed S. , Fathy Maha Abdelhamid , Sharaf el din Mustafa taha Abdelfattah
Published: October 2019

Background

Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder characterized by obesity, hyperandrogenism, and insulin resistance. Intercellular adhesion molecule-1 (ICAM-1) is a proinflammatory and proatherogenic cytokine which is associated with atherosclerosis, insulin resistance, and cardiovascular disease (CVD). The pathogenesis of PCOS is not precisely known. Thus, the purpose of this study was to investigate the potential role of ICAM-1 expression and serum ICAM-1 concentrations in pathogenesis of PCOS. Moreover, we aimed to evaluate the possible relationship between ICAM-1 gene expression with carotid intima-media thickness as well as clinic-morphological features of PCOS.

Methods

This case control study enrolled 180 patients with PCOS and 120 controls groups and they were stratified according to their fasting plasma glucose (FPG) into three subgroups; normal glucose tolerance (NGT) [n = 75], those with impaired glucose tolerance (IGT) [n = 65], and 40 patients with type 2 diabetes mellitus (T2DM). Circulating ICAM-1 expression levels were determined by real time polymerase chain reaction (RT-PCR). Serum ICAM-1 concentrations were measured using enzyme-linked immunosorbent assay (ELISA).

Results

Our results revealed that PCOS patients had higher values of ICAM-1expression and serum levels. Among PCOS patients, T2DM patients had the highest values of ICAM-1 expression and serum levels compared to IGT and NGT subgroups. The ICAM-1 expression and serum levels were significantly positive correlated with cardiovascular risk and PCOS phenotypes. Linear regression test showed that HOMA-IR was the main predictors of serum ICAM-1 levels in PCOS. Receiver operating characteristic curve (ROC) analysis revealed that, the power of ICAM-1 expression levels was higher than serum ICAM-1 in diagnosis of PCOS and in differentiating T2DM from IGT and NGT subgroups. Interestingly, combination of both ICAM-1 expression and serum levels improved the diagnostic role of serum ICAM-1.

Conclusion

ICAM-1 expression and serum levels were higher in women with PCOS compared to control group also, there was a strong independent association between higher ICAM-1 expression and serum levels with cardiovascular risks in PCOS group.
Isolation and characterization of Chlorella sp. mutants with enhanced thermo- and CO2 tolerances for CO2 sequestration and utilization of flue gases
Authors: Chou Hsiang-Hui , Su Hsiang-Yen , Song Xiang-Di , Chow Te-Jin , Chen Chun-Yen , Chang Jo-Shu , Lee Tse-Min
Published: October 2019

Background

The increasing emission of flue gas from industrial plants contributes to environmental pollution, global warming, and climate change. Microalgae have been considered excellent biological materials for flue gas removal, particularly CO2 mitigation. However, tolerance to high temperatures is also critical for outdoor microalgal mass cultivation. Therefore, flue gas- and thermo-tolerant mutants of Chlorella vulgaris ESP-31 were generated and characterized for their ability to grow under various conditions.

Results

In this study, we obtained two CO2- and thermo-tolerant mutants of Chlorella vulgaris ESP-31, namely, 283 and 359, with enhanced CO2 tolerance and thermo-tolerance by using N-methyl-N-nitro-N-nitrosoguanidine (NTG) mutagenesis followed by screening at high temperature and under high CO2 conditions with the w-zipper pouch selection method. The two mutants exhibited higher photosynthetic activity and biomass productivity than that of the ESP-31 wild type. More importantly, the mutants were able to grow at high temperature (40 °C) and a high concentration of simulated flue gas (25% CO2, 80–90 ppm SO2, 90–100 ppm NO) and showed higher carbohydrate and lipid contents than did the ESP-31 wild type.

Conclusions

The two thermo- and flue gas-tolerant mutants of Chlorella vulgaris ESP-31 were useful for CO2 mitigation from flue gas under heated conditions and for the production of carbohydrates and biodiesel directly using CO2 from flue gas.
Remnants of ancestral larval eyes in an eyeless mollusk? Molecular characterization of photoreceptors in the scaphopod Antalis entalis
Authors: Wollesen Tim , McDougall Carmel , Arendt Detlev
Published: October 2019

Background

Eyes have evolved and been lost multiple times during animal evolution, however, the process of eye loss has only been reconstructed in a few cases. Mollusks exhibit eyes as varied as the octopod camera eye or the gastropod cup eye and are ideal systems for studying the evolution of eyes, photoreceptors, and opsins.

Results

Here, we identify genes related to photoreceptor formation and function in an eyeless conchiferan mollusk, the scaphopod Antalis entalis, and investigate their spatial and temporal expression patterns during development. Our study reveals that the scaphopod early mid-stage trochophore larva has putative photoreceptors in a similar location and with a similar gene expression profile as the trochophore of polyplacophoran mollusks. The apical and post-trochal putative photoreceptors appear to co-express go-opsin, six1/2, myoV, and eya, while expression domains in the posterior foot and pavilion (posterior mantle opening) show co-expression of several other candidate genes but not go-opsin. Sequence analysis reveals that the scaphopod Go-opsin amino acid sequence lacks the functionally important lysine (K296; Schiff base) in the retinal-binding domain, but has not accumulated nonsense mutations and still exhibits the canonical G-protein activation domain.

Conclusions

The scaphopod Go-opsin sequence reported here is the only known example of a bilaterian opsin that lacks lysine K296 in the retinal-binding domain. Although this may render the Go-opsin unable to detect light, the protein may still perform sensory functions. The location, innervation, development, and gene expression profiles of the scaphopod and polyplacophoran apical and post-trochal photoreceptors suggest that they are homologous, even though the scaphopod post-trochal photoreceptors have degenerated. This indicates that post-trochal eyes are not a polyplacophoran apomorphy but likely a molluscan synapomorphy lost in other mollusks. Scaphopod eye degeneration is probably a result of the transition to an infaunal life history and is reflected in the likely functional degeneration of Go-opsin, the loss of photoreceptor shielding pigments, and the scarce expression of genes involved in phototransduction and eye development. Our results emphasize the importance of studying a phylogenetically broad range of taxa to infer the mechanisms and direction of body plan evolution.
Giant mass but small symptoms; huge thrombosis in the right atrium originating from the superior vena cava and protruding to the right ventricle: a case report
Authors: Javanshir Elnaz , Sadat-Ebrahimi Seyyed-Reza , Parvizi Rezayat , Toufan Mehrnoosh , Sate Hosein
Published: October 2019

Background

Thrombosis of the superior vena cava with propagation to the right heart chambers can be seen in the presence of chronic indwelling catheters. Moreover, the idiopathic right atrial thrombi may become entrapped in Chiari’s networks, and idiopathic thrombosis of the superior vena cava may occur rarely because of the underlying coagulation disorders or malignancies.

Case presentation

A 43-year-old Iranian (Persian) woman was admitted to our hospital with palpitation of 2 years’ duration and mild to moderate dyspnea of 10 days’ duration. Her past medical history, basic laboratory test results, and cardiac enzyme measurements were unremarkable. Imaging studies revealed a 1.4-cm × 7.4-cm multilobulated, hypermobile mass in the right atrium, extending into the right ventricle, that appeared to be emanating from the superior vena cava. Moreover, partial filling defects were visible in the distal parts of both right and left pulmonary arteries extending to their branches, suggesting massive pulmonary emboli. The patient’s huge mass and emboli were removed by surgery, and pathologic evaluations confirmed that all of the specimens were thrombosis. A number of mutations known as risk factors of thrombosis were detected during genetic evaluations. However, mild symptoms of the patient along with a huge mass in the right atrium, thrombosis in the superior vena cava, and massive thromboembolism remained unexplained.

Conclusion

Huge and dangerous thrombosis inside the heart and superior vena cava can evolve without expected considerable symptoms. Also, detecting the underlying causes of these thromboses sometimes is not feasible by only checking the prevalent known risk factors. Therefore, comprehensive evaluations should be carried out in these patients.
Antiphospholipid syndrome: a case report with an unusual wide spectrum of clinical manifestations
Authors: Mazzoccoli Carmela , Comitangelo Domenico , D’Introno Alessia , Mastropierro Valeria , Sabbà Carlo , Perrone Antonio
Published: October 2019

Background

Antiphospholipid syndrome (APS) is an autoimmune disease characterized by the occurrence of venous and/or arterial thrombosis, and the detection of circulating antiphospholipid antibodies. The classification criteria for definite APS are actually met when at least one clinical criterion (thrombosis or pregnancy morbidity) is present in association of one laboratory criterion (LAC, aCL antibody or aβ2GPI antibody present on two or more occasions, at least 12 weeks a part), and thrombosis should be confirmed by objective validated criteria. The average age of primary APS patients has been reported to be about 35–40 years and the disease is more common in women than in men.

Case presentation

In this report, we described a rare case of an adult male who presented over a period of 9 years with a wide spectrum of clinical manifestations involving different organs that were not initially diagnosed as APS. Dizziness and syncope were his first clinical symptoms, and a non-bacterial thrombotic endocarditis (NBTE) involving the mitral valve was at first diagnosed. Subsequently, the patient also presented with generalized seizures and subsequent head injury. When the patient was admitted to our clinic with bilateral epistaxis and fever, thrombocytopenia was revealed. Moreover, laboratory examinations showed acute pancreatitis with an increase of levels of inflammation markers.

Conclusion

Based on the patient’s medical history and all the examination results, it was possible to make a diagnosis of primary APS and, starting from diagnosis of thrombocytopenia, we were allowed to conclude that all of manifestation were epi-phenomena of a unique clinical entity, rather than unrelated diseases. Though APS is one of the most common thrombocytophilias, unfortunately, it is not recognized often enough. The lack of prevention in undiagnosed patients may cause severe complications which can in turn result in the death of those patients.
Smart literature review: a practical topic modelling approach to exploratory literature review
Authors: Asmussen Claus Boye , Møller Charles
Published: October 2019

Manual exploratory literature reviews should be a thing of the past, as technology and development of machine learning methods have matured. The learning curve for using machine learning methods is rapidly declining, enabling new possibilities for all researchers. A framework is presented on how to use topic modelling on a large collection of papers for an exploratory literature review and how that can be used for a full literature review. The aim of the paper is to enable the use of topic modelling for researchers by presenting a step-by-step framework on a case and sharing a code template. The framework consists of three steps; pre-processing, topic modelling, and post-processing, where the topic model Latent Dirichlet Allocation is used. The framework enables huge amounts of papers to be reviewed in a transparent, reliable, faster, and reproducible way.
A technical and socioeconomic approach to estimate forest residues as a feedstock for bioenergy in northern Mexico
Authors: Carrasco-Diaz Guadalupe , Perez-Verdin Gustavo , Escobar-Flores Jonathan , Marquez-Linares Marco Antonio
Published: October 2019

Background

Forest residues can be a feasible alternative for converting energy into fuels, electricity, or heat. Compared to other second-generation bioenergy sources, they do not compete for food, are relatively cheap, abundant in forest-rich areas, and more importantly their energy balance is close to zero. Biomass estimations can help design energy strategies to reduce fossil fuels dependency. Because of the land property distribution in Mexico, biomass estimations should consider not only the physical availability, but also the willingness of landowners to extract such raw materials.

Methods

This study presents a methodological approach for evaluating the potential use of forest residues as a feedstock to generate bioenergy in northern Mexico. Remote sensing and field forest inventory were used to estimate the quantity and distribution of forest residues. In addition, a discrete choice analysis evaluated landowners’ preferences towards bioenergy development, including the most important factors that influence their willingness to extract their products and the expected price.

Results and conclusions

Considering both physical and socio-economic aspects, results showed that about 59,000 metric tons per year could be available in the study area. The vast majority of landowners surveyed are willing to extract forest residues, as long as they are presented with extraction plans with the highest income. However, many showed concerns about the environmental impacts this activity can have on soils, plants, and fauna. These results can help evaluate the potential of these resources for bioenergy development.
Glycogenin is Dispensable for Glycogen Synthesis in Human Muscle, and Glycogenin Deficiency Causes Polyglucosan Storage
Authors: Visuttijai Kittichate , Hedberg-Oldfors Carola , Thomsen Christer , Glamuzina Emma , Kornblum Cornelia , Tasca Giorgio , Hernandez-Lain Aurelio , Sandstedt Joakim , Dellgren Göran , Roach Peter , Oldfors Anders
Published: October 2019

Context

Glycogenin is considered to be an essential primer for glycogen biosynthesis. Nevertheless, patients with glycogenin-1 deficiency due to biallelic GYG1 (NM_004130.3) mutations can store glycogen in muscle. Glycogenin-2 has been suggested as an alternative primer for glycogen synthesis in patients with glycogenin-1 deficiency.

Objective

The objective of this article is to investigate the importance of glycogenin-1 and glycogenin-2 for glycogen synthesis in skeletal and cardiac muscle.

Design, Setting, and Patients

Glycogenin-1 and glycogenin-2 expression was analyzed by Western blot, mass spectrometry, and immunohistochemistry in liver, heart, and skeletal muscle from controls and in skeletal and cardiac muscle from patients with glycogenin-1 deficiency.

Results

Glycogenin-1 and glycogenin-2 both were found to be expressed in the liver, but only glycogenin-1 was identified in heart and skeletal muscle from controls. In patients with truncating GYG1 mutations, neither glycogenin-1 nor glycogenin-2 was expressed in skeletal muscle. However, nonfunctional glycogenin-1 but not glycogenin-2 was identified in cardiac muscle from patients with cardiomyopathy due to GYG1 missense mutations. By immunohistochemistry, the mutated glycogenin-1 colocalized with the storage of glycogen and polyglucosan in cardiomyocytes.

Conclusions

Glycogen can be synthesized in the absence of glycogenin, and glycogenin-1 deficiency is not compensated for by upregulation of functional glycogenin-2. Absence of glycogenin-1 leads to the focal accumulation of glycogen and polyglucosan in skeletal muscle fibers. Expression of mutated glycogenin-1 in the heart is deleterious, and it leads to storage of abnormal glycogen and cardiomyopathy.
Aldosterone Reduction Rate After Saline Infusion Test May Be a Novel Prediction in Patients With Primary Aldosteronism
Authors: Nagano Hidekazu , Kono Takashi , Saiga Atsushi , Kubota Yoshihiro , Fujimoto Masanori , Felizola Saulo J A , Ishiwata Kazuki , Tamura Ai , Higuchi Seiichiro , Sakuma Ikki , Hashimoto Naoko , Suzuki Sawako , Koide Hisashi , Takeshita Nobushige , Sakamoto Shinichi , Ban Toshiaki , Yokote Koutaro , Nakamura Yasuhiro , Ichikawa Tomohiko , Uno Takashi , Tanaka Tomoaki
Published: October 2019

Objective

Accurate assessment and localization of aldosterone-producing adenomas (APAs) are essential for the treatment of primary aldosteronism (PA). Although adrenal venous sampling (AVS) is the standard method of reference for subtype diagnosis in PA, controversy exists concerning the criteria for its interpretation. This study aims to determine better indicators that can reliably predict subtypes of PA.

Method

Retrospective, single-cohort analysis including 209 patients with PA who were subjected to AVS. Eighty-two patients whose plasma aldosterone concentrations (PAC) were normalized after surgery were histopathologically or genetically diagnosed with APA. The accuracy of image findings was compared to AVS results. Receiver operating characteristic (ROC) curve analysis between the operated and the no-apparent laterality groups was performed using AVS parameters and loading test for diagnosis of PA.

Result

Agreement between image findings and AVS results was 56.3%. ROC curve analysis revealed that the lateralization index (LI) after adrenocorticotropin stimulation cutoff was 2.40, with 98.8% sensitivity and 97.1% specificity. The contralateral suppression index (CSI) cutoff value was 1.19, with 98.0% sensitivity and 93.9% specificity. All patients over the LI and CSI cutoff values exhibited unilateral subtypes. Among the loading test, the best classification accuracy was achieved using the PAC reduction rate after a saline infusion test (SIT) >33.8%, which yielded 87.2% sensitivity or a PAC after a SIT <87.9 pg/mL with 86.2% specificity for predicting bilateral PA.

Conclusion

The combined criteria of the PAC reduction rate and PAC after the SIT can determine which subset of patients with APA who should be performed AVS for validation.
Effects of Peptide YY on the Hypothalamic-Pituitary-Gonadal Axis in Healthy Men
Authors: Izzi-Engbeaya Chioma , Jones Sophie , Crustna Yoshibye , Machenahalli Pratibha C , Papadopoulou Deborah , Modi Manish , Panayi Christos , Starikova Jessica , Eng Pei Chia , Phylactou Maria , Mills Edouard , Yang Lisa , Ratnasabapathy Risheka , Sykes Mark , Plumptre Isabella , Coumbe Ben , Wing Victoria , Pacuszka Ewa , Bech Paul , Minnion James , Tharakan George , Tan Tricia , Veldhuis Johannes , Abbara Ali , Comninos Alexander N , Dhillo Waljit S
Published: October 2019

Context

Central and peripheral administration of peptide YY (PYY) has potent anorectic effects, and PYY analogs are under development as antiobesity treatments. Recent animal data suggest PYY may also influence the reproductive axis; however the effects of PYY on the human reproductive system are unknown.

Objective

To investigate the effects of PYY administration on the reproductive axis in healthy young men.

Design

Single-blind, randomized, placebo-controlled crossover study.

Setting

Clinical Research Facility, Imperial College Healthcare NHS Trust.

Participants

Eighteen healthy eugonadal men (mean age 24.1 ± 0.9 years, mean body mass index 22.2 ± 0.4 kg/m2).

Intervention

Eight-hour intravenous infusion of 0.4 pmol/kg/min PYY3-36 or rate-matched vehicle infusion.

Main Outcome Measures

Number of luteinizing hormone (LH) pulses, LH, follicle stimulating hormone (FSH), and testosterone levels.

Results

The number of LH pulses (mean number of LH pulses/8 hours: PYY 4.4 ± 0.3 vs vehicle 4.4 ± 0.4, P > .99), LH area under the curve (AUC) (PYY 1503 ± 79 IU.min/L vs vehicle 1574 ± 86 IU.min/L, P = .36), FSH AUC (PYY 1158 ± 513 IU.min/L vs vehicle 1199 ± 476 IU.min/L, P = .49) and testosterone AUC (PYY 10 485 ± 684 IU.min/L vs vehicle 11 133 ± 803 IU.min/L, P = .24) were similar during PYY and vehicle infusions.

Conclusions

Acute intravenous infusion of 0.4 pmol/kg/min PYY does not affect the reproductive axis in healthy men.
Lipid Metabolism Links Nutrient-Exercise Timing to Insulin Sensitivity in Men Classified as Overweight or Obese
Authors: Edinburgh Robert M , Bradley Helen E , Abdullah Nurul-Fadhilah , Robinson Scott L , Chrzanowski-Smith Oliver J , Walhin Jean-Philippe , Joanisse Sophie , Manolopoulos Konstantinos N , Philp Andrew , Hengist Aaron , Chabowski Adrian , Brodsky Frances M , Koumanov Francoise , Betts James A , Thompson Dylan , Wallis Gareth A , Gonzalez Javier T
Published: October 2019

Context

Pre-exercise nutrient availability alters acute metabolic responses to exercise, which could modulate training responsiveness.

Objective

To assess acute and chronic effects of exercise performed before versus after nutrient ingestion on whole-body and intramuscular lipid utilization and postprandial glucose metabolism.

Design

(1) Acute, randomized, crossover design (Acute Study); (2) 6-week, randomized, controlled design (Training Study).

Setting

General community.

Participants

Men with overweight/obesity (mean ± standard deviation, body mass index: 30.2 ± 3.5 kg⋅m-2 for Acute Study, 30.9 ± 4.5 kg⋅m-2 for Training Study).

Interventions

Moderate-intensity cycling performed before versus after mixed-macronutrient breakfast (Acute Study) or carbohydrate (Training Study) ingestion.

Results

Acute Study—exercise before versus after breakfast consumption increased net intramuscular lipid utilization in type I (net change: –3.44 ± 2.63% versus 1.44 ± 4.18% area lipid staining, P < 0.01) and type II fibers (–1.89 ± 2.48% versus 1.83 ± 1.92% area lipid staining, P < 0.05). Training Study—postprandial glycemia was not differentially affected by 6 weeks of exercise training performed before versus after carbohydrate intake (P > 0.05). However, postprandial insulinemia was reduced with exercise training performed before but not after carbohydrate ingestion (P = 0.03). This resulted in increased oral glucose insulin sensitivity (25 ± 38 vs –21 ± 32 mL⋅min-1⋅m-2; P = 0.01), associated with increased lipid utilization during exercise (r = 0.50, P = 0.02). Regular exercise before nutrient provision also augmented remodeling of skeletal muscle phospholipids and protein content of the glucose transport protein GLUT4 (P < 0.05).

Conclusions

Experiments investigating exercise training and metabolic health should consider nutrient-exercise timing, and exercise performed before versus after nutrient intake (ie, in the fasted state) may exert beneficial effects on lipid utilization and reduce postprandial insulinemia.
Nonalcoholic Fatty Liver Disease in Adults: Current Concepts in Etiology, Outcomes, and Management
Authors: Marjot Thomas , Moolla Ahmad , Cobbold Jeremy F , Hodson Leanne , Tomlinson Jeremy W
Published: October 2019

Nonalcoholic fatty liver disease (NAFLD) is a spectrum of disease, extending from simple steatosis to inflammation and fibrosis with a significant risk for the development of cirrhosis. It is highly prevalent and is associated with significant adverse outcomes both through liver-specific morbidity and mortality but, perhaps more important, through adverse cardiovascular and metabolic outcomes. It is closely associated with type 2 diabetes and obesity, and both of these conditions drive progressive disease toward the more advanced stages. The mechanisms that govern hepatic lipid accumulation and the predisposition to inflammation and fibrosis are still not fully understood but reflect a complex interplay between metabolic target tissues including adipose and skeletal muscle, and immune and inflammatory cells. The ability to make an accurate assessment of disease stage (that relates to clinical outcome) can also be challenging. While liver biopsy is still regarded as the gold-standard investigative tool, there is an extensive literature on the search for novel noninvasive biomarkers and imaging modalities that aim to accurately reflect the stage of underlying disease. Finally, although no therapies are currently licensed for the treatment of NAFLD, there are interventions that appear to have proven efficacy in randomized controlled trials as well as an extensive emerging therapeutic landscape of new agents that target many of the fundamental pathophysiological processes that drive NAFLD. It is highly likely that over the next few years, new treatments with a specific license for the treatment of NAFLD will become available.
Poverty in lesbian, gay, bisexual, transgender, queer, and two-spirit (LGBTQ2S+) populations in Canada: an intersectional review of the literature
Authors: Kia Hannah , Robinson Margaret , MacKay Jenna , Ross Lori E.
Published: October 2019

Despite the prominence of poverty in lesbian, gay, bisexual, transgender, queer, two-spirit, and other sexual and gender minorities (LGBTQ2S+) in Canada, studies that centre the material conditions of these groups as sites of inquiry remain scant. Accordingly, in this paper we present an intersectional narrative review of the limited Canadian literature on LGBTQ2S+ poverty. We examine 39 studies, published between 2000 and 2018, that report Canadian data on poverty in LGBTQ2S+ youth, older adults, racial minorities and Indigenous groups. We highlight intersectional differences reflected across these axes of social location, and consider research, policy and practice implications of our analysis.
High-Throughput Mass Spectrometry Assay for Quantifying β-Amyloid 40 and 42 in Cerebrospinal Fluid
Authors: Weber Darren M , Tran Diana , Goldman Scott M , Taylor Steven W , Ginns Edward I , Lagier Robert J , Rissman Robert A , Brewer James B , Clarke Nigel J
Published: October 2019

BACKGROUND

The ratio of β-amyloid 1–42 (Aβ42) to Aβ40 in cerebrospinal fluid (CSF) may be useful for evaluating Alzheimer disease (AD), but quantification is limited by factors including preanalytical analyte loss. We developed an LC-MS/MS assay that limits analyte loss. Here we describe the analytical characteristics of the assay and its performance in differentiating patients with AD from non-AD dementia and healthy controls.

METHODS

To measure Aβ42/Aβ40, we used unique proteolytically derived C-terminal peptides as surrogate markers of Aβ40 and Aβ42, which were analyzed and quantified by LC-MS/MS. The assay was analytically validated and applied to specimens from individuals with clinically diagnosed AD (n = 102), mild cognitive impairment (n = 37), and non-AD dementias (n = 22), as well as from healthy controls (n = 130). Aβ42/Aβ40 values were compared with APOE genotype inferred from phenotype, also measured by LC-MS/MS.

RESULTS

The assay had a reportable range of 100 to 25000 pg/mL, a limit of quantification of 100 pg/mL, recoveries between 93% and 111%, and intraassay and interassay CV <15% for both peptides. An Aβ42/Aβ40 ratio cutoff of <0.16 had a clinical sensitivity of 78% for distinguishing patients with AD from non-AD dementia (clinical specificity, 91%) and from healthy controls (clinical specificity, 81%). The Aβ42/Aβ40 ratio decreased significantly (P < 0.001) with increasing dose of APOE4 alleles.

CONCLUSIONS

This assay can be used to determine Aβ42/Aβ40 ratios, which correlate with the presence of AD.
Multicenter Evaluation of Circulating Cell-Free DNA Extraction and Downstream Analyses for the Development of Standardized (Pre)analytical Work Flows
Authors: Lampignano Rita , Neumann Martin H.D , Weber Sabrina , Kloten Vera , Herdean Andrei , Voss Thorsten , Groelz Daniel , Babayan Anna , Tibbesma Marco , Schlumpberger Martin , Chemi Francesca , Rothwell Dominic G , Wikman Harriet , Galizzi Jean-Pierre , Riise Bergheim Inger , Russnes Hege , Mussolin Benedetta , Bonin Serena , Voigt Christine , Musa Hanny , Pinzani Pamela , Lianidou Evi , Brady Ged , Speicher Michael R , Pantel Klaus , Betsou Fay , Schuuring Ed , Kubista Mikael , Ammerlaan Wim , Sprenger-Haussels Markus , Schlange Thomas , Heitzer Ellen
Published: October 2019

BACKGROUND

In cancer patients, circulating cell-free DNA (ccfDNA) can contain tumor-derived DNA (ctDNA), which enables noninvasive diagnosis, real-time monitoring, and treatment susceptibility testing. However, ctDNA fractions are highly variable, which challenges downstream applications. Therefore, established preanalytical work flows in combination with cost-efficient and reproducible reference materials for ccfDNA analyses are crucial for analytical validity and subsequently for clinical decision-making.

METHODS

We describe the efforts of the Innovative Medicines Initiative consortium CANCER-ID (http://www.cancer-id.eu) for comparing different technologies for ccfDNA purification, quantification, and characterization in a multicenter setting. To this end, in-house generated mononucleosomal DNA (mnDNA) from lung cancer cell lines carrying known TP53 mutations was spiked in pools of plasma from healthy donors generated from 2 different blood collection tubes (BCTs). ccfDNA extraction was performed at 15 partner sites according to their respective routine practice. Downstream analysis of ccfDNA with respect to recovery, integrity, and mutation analysis was performed centralized at 4 different sites.

RESULTS

We demonstrate suitability of mnDNA as a surrogate for ccfDNA as a process quality control from nucleic acid extraction to mutation detection. Although automated extraction protocols and quantitative PCR-based quantification methods yielded the most consistent and precise results, some kits preferentially recovered spiked mnDNA over endogenous ccfDNA. Mutated TP53 fragments derived from mnDNA were consistently detected using both next-generation sequencing-based deep sequencing and droplet digital PCR independently of BCT.

CONCLUSIONS

This comprehensive multicenter comparison of ccfDNA preanalytical and analytical work flows is an important contribution to establishing evidence-based guidelines for clinically feasible (pre)analytical work flows.