bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute treatment of venous thromboembolism
Authors: Becattini Cecilia , Agnelli Giancarlo
Published: January 2020

All patients with venous thromboembolism (VTE) should receive anticoagulant treatment in the absence of absolute contraindications. Initial anticoagulant treatment is crucial for reducing mortality, preventing early recurrences, and improving long-term outcome. Treatment and patient disposition should be tailored to the severity of clinical presentation, to comorbidities, and to the potential to receive appropriate care in the outpatient setting. Direct oral anticoagulants (DOACs) used in fixed doses without laboratory monitoring are the agents of choice for the treatment of acute VTE in the majority of patients. In comparison with conventional anticoagulation (parenteral anticoagulants followed by vitamin K antagonists), these agents showed improved safety (relative risk [RR] of major bleeding, 0.61; 95% confidence interval [CI], 0.45-0.83) with a similar risk of recurrence (RR, 0.90; 95% CI, 0.77-1.06). Vitamin K antagonists or low molecular weight heparins are still alternatives to DOACs for the treatment of VTE in specific patient categories such as those with severe renal failure or antiphospholipid syndrome, or cancer, respectively. In addition to therapeutic anticoagulation, probably less than 10% of patients require reperfusion by thrombolysis or interventional treatments; those patients are hemodynamically unstable with acute pulmonary embolism, and a minority of them have proximal limb-threatening deep vein thrombosis (DVT). The choice of treatment should be driven by the combination of evidence from clinical trials and by local expertise. The majority of patients with acute DVT and a proportion of selected hemodynamically stable patients with acute pulmonary embolism can be safely managed as outpatients.
Long-term treatment of venous thromboembolism
Authors: Kearon Clive , Kahn Susan R.
Published: January 2020

The most important decision in the long-term treatment of venous thromboembolism (VTE) is how long to anticoagulate. VTE provoked by a reversible risk factor, or a first unprovoked isolated distal deep vein thrombosis (DVT), generally should be treated for 3 months. VTE provoked by a persistent or progressive risk factor (eg, cancer), or a second unprovoked proximal DVT or PE, is generally treated indefinitely. First unprovoked proximal DVT or PE may be treated for 3 to 6 months or indefinitely. Male sex, presentation as PE (particularly if concomitant proximal DVT), a positive d-dimer test after stopping anticoagulation, an antiphospholipid antibody, low risk of bleeding, and patient preference favor indefinite anticoagulation. The type of indefinite anticoagulation is of secondary importance. Low-dose oral Xa inhibitors are convenient and are thought to have a lower risk of bleeding; they are less suitable if there is a higher risk for recurrence. For cancer-associated VTE, we now prefer full-dose oral Xa inhibitors over low-molecular-weight heparin, with gastrointestinal lesions being a relative contraindication. Graduated compression stockings are not routinely indicated after DVT, but are encouraged if there is persistent leg swelling or if a trial of stockings improves symptoms. Medications have a limited role in the treatment of postthrombotic syndrome. After PE, patients should have clinical surveillance for chronic thromboembolic pulmonary hypertension (CTEPH), with ventilation-perfusion scanning and echocardiography being the initial diagnostic tests if CTEPH is a concern. Patients with CTEPH and other symptomatic patients with extensive residual perfusion defects should be evaluated for endarterectomy, balloon pulmonary angioplasty, or vasodilator therapies.
Highly Efficient Synthesis of Carbon-Based Molybdenum Phosphide Nanoparticles for Electrocatalytic Hydrogen Evolution
Authors: Li Yang , Cai Lun , Huang Qilin , Liu Jun , Tang Ranran , Zhou Wenhan
Published: January 2020

Molybdenum phosphide in transition metal phosphides members are considered as an attractive electrocatalyst for hydrogen evolution reaction (HER). However, its unsatisfactory stability and conductivity in an alkaline environment has dragged on its development. Here, we successfully introduced N, C co-doped MoP (MoP-NC) nanoparticles by a simple and efficient two-step synthesis method using urea as a carbon source into the molybdenum phosphide system. The cheapness of urea and the excellent carbon to nitrogen ratio remove the obstacles ahead of the development of MoP-NC composites. The obtained composites have excellent HER electrocatalytic activity and stability in 1-M potassium hydroxide (KOH) solution, which requires only an overpotential of 131 mV to achieve a current density of 10 mA cm−2 and exhibits negligible performance degradation after 1000 CV cycles.
Students’ “teleological misconceptions” in evolution education: why the underlying design stance, not teleology per se, is the problem
Authors: Kampourakis Kostas
Published: January 2020

Teleology, explaining the existence of a feature on the basis of what it does, is usually considered as an obstacle or misconception in evolution education. Researchers often use the adjective “teleological” to refer to students’ misconceptions about purpose and design in nature. However, this can be misleading. In this essay, I explain that teleology is an inherent feature of explanations based on natural selection and that, therefore, teleological explanations are not inherently wrong. The problem we might rather address in evolution education is not teleology per se but the underlying “design stance”. With this I do not refer to creationism/intelligent design, and to the inference to a creator from the observation of the apparent design in nature (often described as the argument from design). Rather, the design stance refers to the intuitive perception of design in nature in the first place, which seems to be prevalent and independent from religiosity in young ages. What matters in evolution education is not whether an explanation is teleological but rather the underlying consequence etiology: whether a trait whose presence is explained in teleological terms exists because of its selection for its positive consequences for its bearers, or because it was intentionally designed, or simply needed, for this purpose. In the former case, the respective teleological explanation is scientifically legitimate, whereas in the latter case it is not. What then should be investigated in evolution education is not whether students provide teleological explanations, but which consequence etiologies these explanations rely upon. Addressing the design stance underlying students’ teleological explanations could be a main aim of evolution education.
Multi-year maintenance planning framework using multi-attribute utility theory and genetic algorithms
Authors: Allah Bukhsh Zaharah , Stipanovic Irina , Doree Andre G.
Published: January 2020

This paper introduces a comprehensive framework for the development of optimal multi-year maintenance plans for a large number of bridges. A maintenance plan is said to be optimal when, within the given budget, a maximum number of bridges can be maintained in the best possible year, achieving maximum performance with minimum socio-economic impact. The framework incorporates heuristic rules, multi-attribute utility theory, discrete Markov chain process, and genetic algorithms to find an optimal balance between limited budgets and performance requirements. The applicability of the proposed framework is illustrated on an extensive case study of highway bridges. The framework enables asset owners to execute various planning scenarios under different budget and performance requirements, where each resulting plan is optimal. The focus of this study has mainly been on highway bridges, however the framework is general and can be applied to any other infrastructure asset type.
DeepECA: an end-to-end learning framework for protein contact prediction from a multiple sequence alignment
Authors: Fukuda Hiroyuki , Tomii Kentaro
Published: January 2020

Background

Recently developed methods of protein contact prediction, a crucially important step for protein structure prediction, depend heavily on deep neural networks (DNNs) and multiple sequence alignments (MSAs) of target proteins. Protein sequences are accumulating to an increasing degree such that abundant sequences to construct an MSA of a target protein are readily obtainable. Nevertheless, many cases present different ends of the number of sequences that can be included in an MSA used for contact prediction. The abundant sequences might degrade prediction results, but opportunities remain for a limited number of sequences to construct an MSA. To resolve these persistent issues, we strove to develop a novel framework using DNNs in an end-to-end manner for contact prediction.

Results

We developed neural network models to improve precision of both deep and shallow MSAs. Results show that higher prediction accuracy was achieved by assigning weights to sequences in a deep MSA. Moreover, for shallow MSAs, adding a few sequential features was useful to increase the prediction accuracy of long-range contacts in our model. Based on these models, we expanded our model to a multi-task model to achieve higher accuracy by incorporating predictions of secondary structures and solvent-accessible surface areas. Moreover, we demonstrated that ensemble averaging of our models can raise accuracy. Using past CASP target protein domains, we tested our models and demonstrated that our final model is superior to or equivalent to existing meta-predictors.

Conclusions

The end-to-end learning framework we built can use information derived from either deep or shallow MSAs for contact prediction. Recently, an increasing number of protein sequences have become accessible, including metagenomic sequences, which might degrade contact prediction results. Under such circumstances, our model can provide a means to reduce noise automatically. According to results of tertiary structure prediction based on contacts and secondary structures predicted by our model, more accurate three-dimensional models of a target protein are obtainable than those from existing ECA methods, starting from its MSA. DeepECA is available from https://github.com/tomiilab/DeepECA.
Integrative analysis of time course metabolic data and biomarker discovery
Authors: Jendoubi Takoua , Ebbels Timothy M. D.
Published: January 2020

Background

Metabolomics time-course experiments provide the opportunity to understand the changes to an organism by observing the evolution of metabolic profiles in response to internal or external stimuli. Along with other omic longitudinal profiling technologies, these techniques have great potential to uncover complex relations between variations across diverse omic variables and provide unique insights into the underlying biology of the system. However, many statistical methods currently used to analyse short time-series omic data are i) prone to overfitting, ii) do not fully take into account the experimental design or iii) do not make full use of the multivariate information intrinsic to the data or iv) are unable to uncover multiple associations between different omic data. The model we propose is an attempt to i) overcome overfitting by using a weakly informative Bayesian model, ii) capture experimental design conditions through a mixed-effects model, iii) model interdependencies between variables by augmenting the mixed-effects model with a conditional auto-regressive (CAR) component and iv) identify potential associations between heterogeneous omic variables by using a horseshoe prior.

Results

We assess the performance of our model on synthetic and real datasets and show that it can outperform comparable models for metabolomic longitudinal data analysis. In addition, our proposed method provides the analyst with new insights on the data as it is able to identify metabolic biomarkers related to treatment, infer perturbed pathways as a result of treatment and find significant associations with additional omic variables. We also show through simulation that our model is fairly robust against inaccuracies in metabolite assignments. On real data, we demonstrate that the number of profiled metabolites slightly affects the predictive ability of the model.

Conclusions

Our single model approach to longitudinal analysis of metabolomics data provides an approach simultaneously for integrative analysis and biomarker discovery. In addition, it lends better interpretation by allowing analysis at the pathway level. An accompanying package for the model has been developed using the probabilistic programming language . The package offers user-friendly functions for simulating data, fitting the model, assessing model fit and postprocessing the results. The main aim of the package is to offer freely accessible resources for integrative longitudinal analysis for metabolomics scientists and various visualization functions easy-to-use for applied researchers to interpret results.
Fossils from South China redefine the ancestral euarthropod body plan
Authors: Aria Cédric , Zhao Fangchen , Zeng Han , Guo Jin , Zhu Maoyan
Published: January 2020

Background

Early Cambrian Lagerstätten from China have greatly enriched our perspective on the early evolution of animals, particularly arthropods. However, recent studies have shown that many of these early fossil arthropods were more derived than previously thought, casting uncertainty on the ancestral euarthropod body plan. In addition, evidence from fossilized neural tissues conflicts with external morphology, in particular regarding the homology of the frontalmost appendage.

Results

Here we redescribe the multisegmented megacheiransFortiforcepsandJianfengiaand describeSklerolibyon maomimagen. et sp. nov., which we place in Jianfengiidae, fam. nov. (in Megacheira, emended). We find that jianfengiids show high morphological diversity among megacheirans, both in trunk ornamentation and head anatomy, which encompasses from 2 to 4 post-frontal appendage pairs. These taxa are also characterized by elongate podomeres likely forming seven-segmented endopods, which were misinterpreted in their original descriptions. Plesiomorphic traits also clarify their connection with more ancestral taxa. The structure and position of the “great appendages” relative to likely sensory antero-medial protrusions, as well as the presence of optic peduncles and sclerites, point to an overall homology with the anterior head of radiodontans. This is confirmed by our Bayesian phylogeny, which places jianfengiids as the basalmost euarthropods, paraphyletic with other megacheirans, and in contiguity with isoxyids and radiodontans.

Conclusions

Sklerolibyonand other jianfengiids expand the disparity of megacheirans and suggest that the common euarthropod ancestor possessed a remarkable phenotypic variability associated with the externalized cephalon, as well as endopods that were already heptopodomerous, which differs from previous hypotheses and observations. These animals also demonstrate that the frontalmost pair of arthrodized appendage is homologous between radiodontans and megacheirans, refuting the claim that the radiodontan frontal appendages evolved into the euarthropod labrum, and questioning its protocerebral identity. This evidence based on external anatomy now constitutes a solid benchmark upon which we should address issues of homology, with the help of carefully examined palaeoneurological data.
Adaptive divergence in shell morphology in an ongoing gastropod radiation from Lake Malawi
Authors: Van Bocxlaer Bert , Ortiz-Sepulveda Claudia M. , Gurdebeke Pieter R. , Vekemans Xavier
Published: January 2020

Background

Ecological speciation is a prominent mechanism of diversification but in many evolutionary radiations, particularly in invertebrates, it remains unclear whether supposedly critical ecological traits drove or facilitated diversification. As a result, we lack accurate knowledge on the drivers of diversification for most evolutionary radiations along the tree of life. Freshwater mollusks present an enigmatic example: Putatively adaptive radiations are being described in various families, typically from long-lived lakes, whereas other taxa represent celebrated model systems in the study of ecophenotypic plasticity. Here we examine determinants of shell-shape variation in three nominal species of an ongoing ampullariid radiation in the Malawi Basin (Lanistes nyassanus, L. solidus and Lanistes sp. (ovum-like)) with a common garden experiment and semi-landmark morphometrics.

Results

We found significant differences in survival and fecundity among these species in contrasting habitats. Morphological differences observed in the wild persisted in our experiments for L. nyassanus versus L. solidus and L. sp. (ovum-like), but differences between L. solidus and L. sp. (ovum-like) disappeared and re-emerged in the F1 and F2 generations, respectively. These results indicate that plasticity occurred, but that it is not solely responsible for the observed differences. Our experiments provide the first unambiguous evidence for genetic divergence in shell morphology in an ongoing freshwater gastropod radiation in association with marked fitness differences among species under controlled habitat conditions.

Conclusions

Our results indicate that differences in shell morphology among Lanistes species occupying different habitats have an adaptive value. These results also facilitate an accurate reinterpretation of morphological variation in fossil Lanistes radiations, and thus macroevolutionary dynamics. Finally, our work testifies that the shells of freshwater gastropods may retain signatures of adaptation at low taxonomic levels, beyond representing an evolutionary novelty responsible for much of the diversity and disparity in mollusks altogether.
The transcriptional correlates of divergent electric organ discharges in Paramormyrops electric fish
Authors: Losilla Mauricio , Luecke David Michael , Gallant Jason R.
Published: January 2020

Background

Understanding the genomic basis of phenotypic diversity can be greatly facilitated by examining adaptive radiations with hypervariable traits. In this study, we focus on a rapidly diverged species group of mormyrid electric fish in the genusParamormyrops, which are characterized by extensive phenotypic variation in electric organ discharges (EODs). The main components of EOD diversity are waveform duration, complexity and polarity. Using an RNA-sequencing based approach, we sought to identify gene expression correlates for each of these EOD waveform features by comparing 11 specimens ofParamormyropsthat exhibit variation in these features.

Results

Patterns of gene expression amongParamormyropsare highly correlated, and 3274 genes (16%) were differentially expressed. Using our most restrictive criteria, we detected 145–183 differentially expressed genes correlated with each EOD feature, with little overlap between them. The predicted functions of several of these genes are related to extracellular matrix, cation homeostasis, lipid metabolism, and cytoskeletal and sarcomeric proteins. These genes are of significant interest given the known morphological differences between electric organs that underlie differences in the EOD waveform features studied.

Conclusions

In this study, we identified plausible candidate genes that may contribute to phenotypic differences in EOD waveforms among a rapidly diverged group of mormyrid electric fish. These genes may be important targets of selection in the evolution of species-specific differences in mate-recognition signals.
Larva of greater wax moth Galleria mellonella is a suitable alternative host for the fish pathogen Francisella noatunensis subsp. orientalis
Authors: Djainal Winarti Achmad Sarmin , Shahin Khalid , Metselaar Matthijs , Adams Alexandra , Desbois Andrew P.
Published: January 2020

Background

Francisella noatunensis subsp. orientalis (Fno) is the etiological agent of francisellosis in cultured warm water fish, such as tilapia. Antibiotics are administered to treat the disease but a better understanding of Fno infection biology will inform improved treatment and prevention measures. However, studies with native hosts are costly and considerable benefits would derive from access to a practical alternative host. Here, larvae of Galleria mellonella were assessed for suitability to study Fno virulence.

Results

Larvae were killed by Fno in a dose-dependent manner but the insects could be rescued from lethal doses of bacteria by antibiotic therapy. Infection progression was assessed by histopathology (haematoxylin and eosin staining, Gram Twort and immunohistochemistry) and enumeration of bacteria recovered from the larval haemolymph on selective agar. Fno was phagocytosed and could survive intracellularly, which is consistent with observations in fish. Virulence of five Fno isolates showed strong agreement between G. mellonella and red Nile tilapia hosts.

Conclusions

This study shows that an alternative host, G. mellonella, can be applied to understand Fno infections, which will assist efforts to identify solutions to piscine francisellosis thus securing the livelihoods of tilapia farmers worldwide and ensuring the production of this important food source.
The effect of gestational diabetes mellitus on sufentanil consumption after cesarean section: a prospective cohort study
Authors: Yang Chen , Geng Wei Lian , Hu Jianying , Huang Shaoqiang
Published: January 2020

Background

Previous studies have shown that patients with long-term diabetes require more opioids after surgery than patients without diabetes. Gestational diabetes mellitus (GDM) normally only lasts for a brief period; nevertheless, its effect on sufentanil consumption after cesarean section is unknown.

Methods

This prospective cohort study included two groups: a GDM group (n = 32) and a matched non-GDM (NGDM) group (n = 32). All patients underwent routine combined spinal-epidural anesthesia for cesarean delivery. Sufentanil consumption through an intravenous patient-controlled analgesia (PCA) pump, the frequency of PCA requests, and visual analog scale (VAS) scores 6 and 24 h after surgery were compared between groups.

Results

Sufentanil consumption (μg) 6 h after surgery was higher in the GDM group than in the NGDM group (24.0 ± 6.6 vs 20.1 ± 5.7,P = 0.023). PCA was used more frequently 6 and 24 h after surgery by the GDM group than by the NGDM group (1[0–2] vs 0[0–1],P = 0.001; 6 [1–5] vs 3 [1, 2, 6–8],P = 0.001, respectively). The VAS score during activity 24 h after surgery was higher in the GDM group than in the NGDM group (5 [2, 3] vs 5 [1, 2], respectively,P = 0.03).

Conclusion

Pregnant women with GDM require more opioids during the immediate postoperative period after cesarean section than those without GDM.

Clinical trials registration

No. ChiCTR1800016014, ChenYang, May 6th 2018.
Impact of guideline-recommended versus non-guideline-recommended β-blocker and Doppler echocardiographic parameters on 1-year mortality in Thai ischemic cardiomyopathy patients: A prospective multicenter registry
Authors: Wongpraparut Nattawut , Siwamogsatham Sarawut , Thongsri Tomorn , Ngamjanyaporn Pornchai , Phrommintikul Arintaya , Jirajarus Kompoj , Tangcharoen Tarinee , Bhumimuang Kid , Kaewsuwanna Pinij , Krittayaphong Rungroj , Pongakasira Rungtiwa , White Harvey D.
Published: January 2020

Background

Ischemic cardiomyopathy is a high-cost, resource-intensive public health burden that is associated with a 1-year mortality rate of about 16% in western population. Different in patient ethnicity and pattern of practice may impact the clinical outcome. We aim to determine 1-year mortality and to identify factors that significantly predicts 1-year mortality of Thai patients with ischemic cardiomyopathy.

Methods

This prospective multicenter registry enrolled consecutive Thai patients that were diagnosed with ischemic cardiomyopathy at 9 institutions located across Thailand. Patients with left ventricular function < 40% and one of the following criteria were included: 1) presence of epicardial coronary stenoses > 75% in the left main or proximal left anterior descending artery or coronary angiography, and/or two major epicardial coronary stenoses; 2) prior myocardial infarction; 3) prior revascularization by coronary artery bypass graft or percutaneous coronary intervention; or, 4) magnetic resonance imaging pattern compatible with ischemic cardiomyopathy. Baseline clinical characteristics, coronary and echocardiographic data were recorded. The 1-year clinical outcome was pre-specified.

Results

Four hundred and nineteen patients were enrolled. Thirty-nine patients (9.9%) had died at 1 year, with 27 experiencing cardiovascular death, and 12 experiencing non-cardiovascular death. A comparison between patients who were alive and patients who were dead at 1 year revealed lower baseline left ventricular ejection fraction (LVEF) (26.7 ± 7.6% vs 30.2 ± 7.8%; p = 0.021), higher left ventricular end-diastolic volume (LVEDV) (185.8 ± 73.2 ml vs 155.6 ± 64.2 ml; p = 0.014), shorter mitral valve deceleration time (142.9 ± 57.5 ml vs 182.4 ± 85.7 ml; p = 0.041), and lower use of statins (94.7% vs 99.7%; p = 0.029) among deceased patients. Patients receiving guideline-recommended β-blockers had lower mortality than patients receiving non-guideline-recommended β-blockers (8.1% vs 18.2%; p = 0.05).

Conclusions

The results of this study revealed a 9.9% 1-year mortality rate among Thai ischemic cardiomyopathy patients. Doppler echocardiographic parameters significantly associated with 1-year mortality were LVEF, LVEDV, mitral E velocity, and mitral valve deceleration time. The use of non-guideline-recommended β-blockers rather than guideline recommended β-blockers were associated with increased with 1-year mortality. Guidelines recommended β-blockers should be preferred.

Trial registration

Thai Clinical Trials Registry TCTR20190722002. Registered 22 July 2019. “Retrospectively registered”.
Platelet to lymphocyte ratio predicting 6-month primary patency of drug-coated balloon for femoropopliteal disease
Authors: Zhen Yanhua , Chang Zhihui , Liu Zhaoyu , Zheng Jiahe
Published: January 2020

Background

Inflammatory reaction is an essential factor in the occurrence, development and prognosis of femoropopliteal disease (FPD). The ratio of platelets to lymphocytes (PLR) is a new indicator reflecting platelet aggregation and burden of systemic inflammation. Our study is to explore the association between preoperative platelet-to-lymphocyte ratio (pre-PLR) and 6-month primary patency (PP) after drug-coated balloon (DCB) in FPD.

Methods

There were 70 patients who underwent DCB for FPD contained in the study. According to 6-month PP, patients were divided into group A (PP ≥6 months, n = 54) and group B (PP < 6 months, n = 16). Logistic regression analysis was used to identify potential predictors for 6-month PP after DCB in FPD. A receiver operating characteristic (ROC) curve analysis was used to identify the cut-off value of pre-PLR to predict 6-month PP.

Results

Logistic regression analysis showed that pre-PLR (OR: 1.008, 95% CI: 1.001–1.016, P = 0.031) and lesion length > 10 cm (OR: 4.305, 95% CI: 1.061–17.465, P = 0.041) were independently predictive for 6-month PP. The cutoff value of pre-PLR obtained from the ROC analysis was 127.35 to determine 6-month PP with the area of 0.839. Subgroup analysis was conducted based on the cutoff value of pre-PLR. The 6-month PP in the group of pre-PLR < 127.35 was higher than that of pre-PLR ≥ 127.35 group (p < 0.001).

Conclusions

The present study indicated that an elevated pre-PLR was an effective additional indicator for predicting early PP in FPD after DCB.
Sero-prevalence and risk factors of brucellosis among suspected febrile patients attending a referral hospital in southern Saudi Arabia (2014–2018)
Authors: Alkahtani Abdullah M. , Assiry Mohammed M. , Chandramoorthy Harish C. , Al-Hakami Ahmed M. , Hamid Mohamed E.
Published: January 2020

Background

Human brucellosis is an infectious zoonotic disease caused byBrucellaspp. It is one of the most public health problems that remains largely neglected in developing counties, including Saudi Arabia. Brucellosis is particularly prevalent among rural people who have constant contact with livestock.

Methods

A cross-sectional sero-epidemiological study conducted in Aseer Central Hospital, South Saudi Arabia, between 2014 and 2018 among 7567 patients. Serum samples were analyzed forBrucellaantibodies using slide agglutination test. Serology results and patient’s demographic data were analyzed by GraphPad Prism. Results were presented as mean ± SEM and differences between two groups were assessed by t-test andp < 0.05 was considered significant.

Results

The prevalence of brucellosis among the admitted suspected 7567 cases was 12.8% (10.4–15.7%; CI 95%). The highest prevalence rate was detected during 2015, the rate decreased to the lowest level during the last three years (p < 0.05). Higher rate of brucellosis was observed among males than females (p < 0.05) and most cases were reported during summer season (p < 0.05). The highest prevalence rate was observed in age group 21–40 year old (40.5%) followed by 41–60 years (27.7%). The lowest prevalence rate was noticed in old and young children (15 and 3%, respectively). Cross-transmission of brucellosis was seen within family (1%) and high titers (> 1280) was noticed in 22% of the hospitalized patients. The major symptoms were fatigue, hyperhidrosis, fever and joint pain.

Conclusion

Our findings showed a high prevalence of human brucellosis among suspected patients in Aseer region. This indicates that clinical suspicion is a valid criterion and the endemic nature of the disease. The disease status requires early laboratory detection and confirmation to start prompt treatment to decrease patients suffering.
T2 mapping of molecular subtypes of WHO grade II/III gliomas
Authors: Kern Maike , Auer Timo Alexander , Picht Thomas , Misch Martin , Wiener Edzard
Published: January 2020

Background

According to the new WHO classification from 2016, molecular profiles have shown to provide reliable information about prognosis and treatment response. The purpose of our study is to evaluate the diagnostic potential of non-invasive quantitative T2 mapping in the detection of IDH1/2 mutation status in grade II-III gliomas.

Methods

Retrospective evaluation of MR examinations in 30 patients with histopathological proven WHO-grade II (n = 9) and III (n = 21) astrocytomas (18 IDH-mutated, 12 IDH-wildtype). Consensus annotation by two observers by use of ROI’s in quantitative T2-mapping sequences were performed in all patients. T2 relaxation times were measured pixelwise.

Results

A significant difference (p = 0,0037) between the central region of IDH-mutated tumors (356,83 ± 114,97 ms) and the IDH-wildtype (199,92 ± 53,13 ms) was found. Furthermore, relaxation times between the central region (322,62 ± 127,41 ms) and the peripheral region (211,1 ± 74,16 ms) of WHO grade II and III astrocytomas differed significantly (p = 0,0021). The central regions relaxation time of WHO-grade II (227,44 ± 80,09 ms) and III gliomas (322,62 ± 127,41 ms) did not differ significantly (p = 0,2276). The difference between the smallest and the largest T2 value (so called “range”) is significantly larger (p = 0,0017) in IDH-mutated tumors (230,89 ± 121,11 ms) than in the IDH-wildtype (96,33 ± 101,46 ms). Interobserver variability showed no significant differences.

Conclusions

Quantitative evaluation of T2-mapping relaxation times shows significant differences regarding the IDH-status in WHO grade II and III gliomas adding important information regarding the new 2016 World Health Organization (WHO) Classification of tumors of the central nervous system. This to our knowledge is the first study regarding T2 mapping and the IDH1/2 status shows that the mutational status seems to be more important for the appearance on T2 images than the WHO grade.
Case report: discovery of 2 gene variants for aromatic L-amino acid decarboxylase deficiency in 2 African American siblings
Authors: Monteleone Berrin , Hyland Keith
Published: January 2020

Background

Aromatic l-amino acid decarboxylase (AADC) deficiency is a rare genetic disorder with heterogeneous phenotypic spectrum resulting from disease-causing variants in the dopa decarboxylase (DDC) gene. Consensus guidelines recommend dopamine agonists, monoamine oxidase inhibitors, and other symptomatic treatments, but most patients have an unrelenting disease course with no response to these therapies.

Case presentation

We describe 2 African American siblings with AADC deficiency and identify 2 DDC gene variants not previously associated with the disorder. The patients were evaluated for cognitive and neurologic impairments. Diagnosis of AADC deficiency was initially based on evaluation of urine and plasma metabolites, followed by targeted DDC gene sequencing. The first patient, a firstborn African American female, had moderate elevations of vanillactic and vanilpyruvic acids, and slight elevation of N-acetylvanilalanine in urine. The second patient, an African American female and younger sibling of the first patient, had low AADC enzyme activity and elevated 3-O-methyldopa levels in plasma. Genetic testing confirmed that both siblings possessed the same 2 DDC gene variants, which were identified as NM_000790.3: c.48C > A (p.Tyr16Ter) and NM_000790.3: c.116G > C (p.Arg39Pro).

Conclusions

This report describes 2 previously unknown patients with AADC deficiency and confirmed the presence of 2 DDC gene variants not previously associated with this disorder. Further research is needed to identify disease-modifying treatments for this devastating neurometabolic disorder. Gene therapy with a recombinant adeno-associated viral vector serotype 2 carrying the gene for the human AADC protein (AAV2-hAADC) is currently in clinical development.
Propionibacterium acnes-associated chronic hypertrophic pachymeningitis followed by refractory otitis media: a case report
Authors: Amano Eiichiro , Uchida Keisuke , Ishihara Tasuku , Otsu Shinichi , Machida Akira , Eishi Yoshinobu
Published: January 2020

Background

Hypertrophic pachymeningitis (HP) is a rare disorder that involves localized or diffuse thickening of the dura mater. HP is associated with various inflammatory, infectious, and malignant diseases, such as rheumatic arthritis, sarcoidosis, anti-neutrophil cytoplasmic antibody-associated vasculitis, IgG4-related disorders, syphilis, tuberculosis, bacterial and fungal infections, cancer, and idiopathic diseases, when evaluation fails to reveal a cause. Among them, chronic infection with Propionibacterium acnes is a rare etiology of HP, and its pathology remains unclear.

Case presentation

An 80-year-old man having refractory otitis media with effusion of the right ear presented with progressive right-sided headache and nausea. Post-contrast brain magnetic resonance imaging revealed right mastoiditis and remarkable thickening of the dura mater and enhancement of pia mater extending from the right middle cranial fossa to the temporal lobe.

HP secondary to middle ear infection was suspected, and a biopsy of the right mastoid was performed. An anaerobic culture of the biopsied right mastoid showed the growth of P. acnes, and histopathological examination using P. acnes-specific monoclonal antibody (PAB antibody) revealed the infiltration of inflammatory cells with P. acnes. Moreover, using PAB antibody, P. acnes was detected in the biopsy specimen of the thickening dura mater. No granulomas were identified in either specimen. HP was resolved with long-term administration of antibiotics and steroids.

Conclusion

This is the first documentation of pathologically demonstrated chronic HP associated with P. acnes infection followed by refractory otitis media. This report showed that chronic latent P. acnes infection induces chronic inflammation.
Characteristics of diffuse retinal nerve fiber layer defects in red-free photographs as observed in optical coherence tomography en face images
Authors: Lim Abegaile Bartolome , Park Ji-Hye , Jung Jae Hoon , Yoo Chungkwon , Kim Yong Yeon
Published: January 2020

Backgroud

To determine whether diffuse retinal nerve fiber layer (RNFL) defects, identified on red-free fundus photographs, could be identified on optical coherence tomography (OCT) en face structural images and to evaluate which factors are related to the different recognition patterns on en face images.

Methods

This retrospective, cross-sectional study included open-angle glaucoma eyes with diffuse RNFL defects in the inferior hemifield, identified in red-free photographs. The corresponding OCT en face structural images were divided into 3 groups: (1) no defect, (2) localized defect, and (3) diffuse defect. We compared the demographic and clinical ocular characteristics among the groups.

Results

A total of 209 eyes from 157 patients were included. The distribution of OCT en face images was: no defect, 25 eyes (11.96%); localized defect, 106 eyes (50.72%); diffuse defect, 78 eyes (37.32%). Logistic regression analysis revealed that eyes with greater mean deviation (P = 0.004) and thicker inferior RNFL (P = 0.008) would be included in the no defect and localized defect groups based on OCT en face images, rather than in the diffuse defect group.

Conclusion

Around half of diffuse RNFL defects identified in the red-free photographs appeared as localized defects in OCT en face images. Mild glaucomatous damage was related to no defect and localized defect groups, classified based on the OCT en face images, in eyes with diffuse photographic RNFL defects. OCT en face images may be helpful in further assessing diffuse RNFL defects seen in red-free photographs in eyes with open-angle glaucoma.
Advancing successful implementation of task-shifted mental health care in low-resource settings (BASIC): protocol for a stepped wedge cluster randomized trial
Authors: Dorsey Shannon , Gray Christine L. , Wasonga Augustine I. , Amanya Cyrilla , Weiner Bryan J. , Belden C. Micha , Martin Prerna , Meza Rosemary D. , Weinhold Andrew K. , Soi Caroline , Murray Laura K. , Lucid Leah , Turner Elizabeth L. , Mildon Robyn , Whetten Kathryn
Published: January 2020

Background

The mental health treatment gap—the difference between those with mental health need and those who receive treatment—is high in low- and middle-income countries. Task-shifting has been used to address the shortage of mental health professionals, with a growing body of research demonstrating the effectiveness of mental health interventions delivered through task-shifting. However, very little research has focused on how to embed, support, and sustain task-shifting in government-funded systems with potential for scale up. The goal of theBuilding and Sustaining Interventions for Children (BASIC)study is to examine implementation policies and practices that predict adoption, fidelity, and sustainment of a mental health intervention in the education sector via teacher delivery and the health sector via community health volunteer delivery.

Methods

BASIC is a Hybrid Type II Implementation-Effectiveness trial. The study design is a stepped wedge, cluster randomized trial involving 7 sequences of 40 schools and 40 communities surrounding the schools. Enrollment consists of 120 teachers, 120 community health volunteers, up to 80 site leaders, and up to 1280 youth and one of their primary guardians. The evidence-based mental health intervention is a locally adapted version of Trauma-focused Cognitive Behavioral Therapy, calledPamoja Tunaweza.Lay counselors are trained and supervised inPamoja Tunawezaby local trainers who are experienced in delivering the intervention and who participated in a Train-the-Trainer model of skills transfer. After the first sequence completes implementation, in-depth interviews are conducted with initial implementing sites’ counselors and leaders. Findings are used to inform delivery of implementation facilitation for subsequent sequences’ sites. We use a mixed methods approach including qualitative comparative analysis to identify necessary and sufficient implementation policies and practices that predict 3 implementation outcomes of interest: adoption, fidelity, and sustainment. We also examine child mental health outcomes and cost of the intervention in both the education and health sectors.

Discussion

The BASIC study will provide knowledge about how implementation of task-shifted mental health care can be supported in government systems that already serve children and adolescents. Knowledge about implementation policies and practices from BASIC can advance the science of implementation in low-resource contexts.

Trial registration

Trial Registration:ClinicalTrials.govIdentifier: NCT03243396. Registered 9th August 2017,https://clinicaltrials.gov/ct2/show/NCT03243396
Evaluation of childhood traumatic experience as a risk factor for alcohol use disorder in adulthood
Authors: Wang Lan , An Cui-Xia , Song Mei , Li Na , Gao Yuan-Yuan , Zhao Xiao-Chuan , Yu Lu-Lu , Wang Yu-Mei , Wang Xue-Yi
Published: January 2020

Background

We aimed to investigate the effect of early-age (prenatal, infant, and childhood) trauma on adulthood alcohol use disorder.

Methods

A total number of 1534 subjects who were born and live in the city of Tangshan were selected. The subjects were divided into three age groups. General demographic data, conditions of the mothers during pregnancy, and condition of the babies at birth, were collected. The diagnosis of alcohol use disorder was based on Structured Clinical Interviews for DSM-IV Axis Disorders (patient version) (SCID). The childhood trauma questionnaire short form (CTQ-SF) [1] and the Lifetime of Experience Questionnaire (LTE-Q) [2] were used to evaluate stress in childhood and adulthood, respectively.

Results

Only male subjects were diagnosed with lifelong alcohol abuse and alcohol dependence. There was no statistically significant difference in the prevalence of lifetime alcohol use disorder (X2 = 4.480, P = 0.345), current alcohol abuse, and current alcohol dependence among the three groups (X2abuse = 2.177, X2depedence = 2.198, P > 0.05). However, higher prevalence of lifetime alcohol use disorders was found in group with higher scores of CTQ (X2 = 9.315, P = 0.009), emotional abuse (X2 = 8.025, P = 0.018), physical abuse (X2 = 20.4080, P < 0.001), but not in the group with higher scores of emotional neglect (X2 = 1.226, P = 0.542), sexual abuse (X2 = 2.779, P = 0.249), physical neglect (X2 = 3.978, P = 0.137), LTE-Q (X2 = 5.415, P = 0.067), and PSQI (X2 = 5.238, P = 0.073). Protective factor for alcohol abuse for men was identified to be heavy drinking (OR = 0.085, 95%CI: 0.011–0.661), and the risk factors for alcohol abuse were identified to be frequent drinking (OR = 2.736, 95%CI: 1.500, 4.988), and consumption of low liquor (OR = 2.563, 95%CI: 1.387, 4.734). Risk factors for alcohol dependence in males were identified to be consumption of low liquor (OR = 5.501, 95%CI: 2.004, 15.103), frequent drinking (OR = 2.680, 95%CI: 1.164, 6.170), and childhood physical abuse (OR = 2.310, 95% CI: 1.026, 5.201).

Conclusion

Traumatic experience during infant and prenatal periods does not have a strong statistical correlation with alcohol use disorders for male adults. However, subjects with high CTQ scores, experience of emotional abuse and physical abuse show a statistically higher prevalence of lifetime alcohol use disorders. Several risk factors including consumption of low liquor, frequent drinking, and childhood physical abuse contribute to alcohol dependence in male adults.
Can participatory video reduce mental illness stigma? Results from a Canadian action-research study of feasibility and impact
Authors: Whitley Rob , Sitter Kathleen C. , Adamson Gavin , Carmichael Victoria
Published: January 2020

Background

Evidence suggests that stigma against people with mental illness remains high. This demands innovative approaches to reduce stigma. One innovative stigma reduction method is participatory video (PV), whereby marginalized people come together to script, film and produce bottom-up educational videos about shared issues. These videos are then shown to target groups. This paper has two objectives (i) to examine the feasibility of using participatory video with people with severe mental illness (SMI); and (ii) to assess viewer impressions of the resultant videos and subsequent subjective impact.

Methods

We conducted a participatory action research study with three workgroups of people with severe mental illness situated in different Canadian cities, who set out to create and disseminate locally-grounded mental-health themed videos. This involved process and outcome evaluation to assess feasibility and impact. Specifically, we (i) observed fidelity to a co-designed action-plan in all three workgroups; (ii) distributed brief purpose-built questionnaires to viewers at organized screenings to assess preliminary impact; and (iii) conducted focus groups with viewers to elicit further impressions of the videos and subsequent subjective impact.

Results

The three workgroups achieved high-fidelity to the action-plan. They successfully produced a total of 26 videos, over double the targeted number, during an 18-month period. Likewise, the workgroups organized 49 screenings at a range of venues attended by 1542 people, again exceeding the action-plan targets. Results from the viewer questionnaires (N = 1104, response rate 72%) indicated that viewers reported that their understandings had improved after watching the videos. Four themes emerged from six viewer focus groups (N = 30), with participants frequently noting that videos were (i) educational and informative; (ii) real and relatable; (iii) attention-grabbing; and (iv) change-inducing.

Conclusions

To our knowledge, this study is the first large-scale multi-site project examining the feasibility and impact of a participatory video program for people with severe mental illness. The results indicate that participatory video is a feasible method in this population and gives preliminary evidence that resultant videos can reduce viewer stigma. Thus, participatory video should be considered a promising practice in the ongoing effort to reduce mental illness stigma.
Is the Philippines ready for HIV self-testing?
Authors: Gohil Jesal , Baja Emmanuel S. , Sy Tyrone Reden , Guevara Ernest Genesis , Hemingway Charlotte , Medina Paul Mark B. , Coppens Leila , Dalmacion Godofreda V. , Taegtmeyer Miriam
Published: January 2020

Background

The Philippines is facing a rapidly rising HIV epidemic among young men who have sex with men (MSM). Testing rates among young populations is poor. HIV self-testing (HIVST) is a promising strategy to address this testing gap. The study’s purpose was to explore the perceived acceptability, feasibility and programmatic challenges of HIVST among key informants and target users.

Method

A qualitative study involving semi-structured interviews and focus group discussions (FGD). We interviewed 15 key informants involved with HIV testing programs or policies and 42 target users in six FGD in Metro Manila. We held separate discussions with high socio-economic MSM (n = 12), urban poor MSM (n = 15) and transgender women (TGW) (n = 15). Results were analysed using a thematic framework approach.

Results

MSM and TGW welcomed the convenience and privacy HIVST could provide. They preferred an inexpensive accurate blood-based kit attained from reputable sites. Key informants at national and local level equally welcomed HIVST but identified a number of policy and regulatory issues. Both groups articulated the challenge of enrolling those who test reactive using HIVST to further testing and treatment in an environment characterised by acute stigma around HIV.

Conclusions

HIVST was found to be highly acceptable to target users and was welcomed as an additional testing approach at national level. Strategic alliances are now needed between stakeholders to proactively deliver a patient-centred HIVST program that could provide an effective, safe means of increasing testing coverage in this escalating context.