bluuebunny/crossref_metadata_2025 huggingface dataset:
Vaccination or mass drug administration against schistosomiasis: a hypothetical cost-effectiveness modelling comparison
Authors: Collyer Benjamin S. , Turner Hugo C. , Hollingsworth T. Déirdre , Keeling Matt J.
Published: October 2019

Background

Schistosomiasis is a neglected tropical disease, targeted by the World Health Organization for reduction in morbidity by 2020. It is caused by parasitic flukes that spread through contamination of local water sources. Traditional control focuses on mass drug administration, which kills the majority of adult worms, targeted at school-aged children. However, these drugs do not confer long-term protection and there are concerns over the emergence of drug resistance. The development of a vaccine against schistosomiasis opens the potential for control methods that could generate long-lasting population-level immunity if they are cost-effective.

Methods

Using an individual-based transmission model, matched to epidemiological data, we compared the cost-effectiveness of a range of vaccination programmes against mass drug administration, across three transmission settings. Health benefit was measured by calculating the heavy-intensity infection years averted by each intervention, while vaccine costs were assessed against robust estimates for the costs of mass drug administration obtained from data. We also calculated a critical vaccination cost, a cost beyond which vaccination might not be economically favorable, by benchmarking the cost-effectiveness of potential vaccines against the cost-effectiveness of mass drug administration, and examined the effect of different vaccine protection durations.

Results

We found that sufficiently low-priced vaccines can be more cost-effective than traditional drugs in high prevalence settings, and can lead to a greater reduction in morbidity over shorter time-scales. MDA or vaccination programmes that target the whole community generate the most health benefits, but are generally less cost-effective than those targeting children, due to lower prevalence of schistosomiasis in adults.

Conclusions

The ultimate cost-effectiveness of vaccination will be highly dependent on multiple vaccine characteristics, such as the efficacy, cost, safety and duration of protection, as well as the subset of population targeted for vaccination. However, our results indicate that if a vaccine could be developed with reasonable characteristics and for a sufficiently low cost, then vaccination programmes can be a highly cost-effective method of controlling schistosomiasis in high-transmission areas. The population-level immunity generated by vaccination will also inevitably improve the chances of interrupting transmission of the disease, which is the long-term epidemiological goal.
Factors associated with food safety practices among food handlers: facility-based cross-sectional study
Authors: Azanaw Jember , Gebrehiwot Mulat , Dagne Henok
Published: October 2019

Objective

The primary objective of this study was to assess factors associated with food safety practices among food handlers in Gondar city food and drinking establishments. The facility-based cross-sectional study was undertaken from March 3 to May 28, 2018, in Gondar city. Simple random sampling method was used to select both establishments and the food handlers. The data were collected through face-to-face interview using pre-tested Amharic version of the questionnaire. Data were entered and coded into Epi info version 7.0.0 and exported to SPSS version 22 for analysis.

Results

One hundred and eighty-eight (49.0%) had good food handling practice out of three hundred and eighty-four food handlers. Marital status (AOR: 0.36, 95% CI 0.05, 0.85), safety training (AOR: 4.01, 95% CI 2.71, 9.77), supervision by health professionals (AOR: 4.10, 95% CI 1.71, 9.77), routine medical checkup (AOR: 8.80, 95% CI 5.04, 15.36), and mean knowledge (AOR: 2.92, 95% CI 1.38, 4.12) were the factors significantly associated with food handling practices. The owners, managers and local health professionals should work on food safety practices improvement.
High frequency audible calls in northern birch mice Sicista betulina in response to handling: effects of individuality, sex and body mass on the acoustics
Authors: Volodin Ilya A. , Klenova Anna V. , Ilchenko Olga G. , Volodina Elena V.
Published: October 2019

Objectives

This is the first study of the sonic and ultrasonic vocalization in a Dipodidae rodent. For the small-sized quadrupedal northern birch mouse Sicista betulina, phylogenetically related to the bipedal jerboas (Dipodidae), we report null results for ultrasonic vocalization and investigate the acoustic cues to individual identity, sex and body size in the discomfort-related high-frequency tonal sonic calls.

Results

We used a parallel audio recording in the sonic and ultrasonic ranges during weighting adult northern birch mice before the scheduled hibernation in captivity. The sonic (audible) high-frequency tonal calls (ranging from 6.21 to 9.86 kHz) were presented in all individuals (7 males and 4 females). The ultrasonic calls lacked in the recordings. Two-way nested ANOVA revealed the effects of caller individual identity on all 10 measured acoustic variables and the effects of sex on four out of 10 measured acoustic variables. Discriminant function analyses with 10 acoustic variables included in the analysis showed 85.5% correct assignment of calls to individual and 79.7% correct assignment of calls to sex; both values significantly exceeded the random values (23.1% and 54.3%, respectively) calculated with randomization procedure. Body mass did not differ between sexes and did not correlate significantly with the acoustic variables.
Random forest-based modelling to detect biomarkers for prostate cancer progression
Authors: Toth Reka , Schiffmann Heiko , Hube-Magg Claudia , Büscheck Franziska , Höflmayer Doris , Weidemann Sören , Lebok Patrick , Fraune Christoph , Minner Sarah , Schlomm Thorsten , Sauter Guido , Plass Christoph , Assenov Yassen , Simon Ronald , Meiners Jan , Gerhäuser Clarissa
Published: October 2019

Background

The clinical course of prostate cancer (PCa) is highly variable, demanding an individualized approach to therapy. Overtreatment of indolent PCa cases, which likely do not progress to aggressive stages, may be associated with severe side effects and considerable costs. These could be avoided by utilizing robust prognostic markers to guide treatment decisions.

Results

We present a random forest-based classification model to predict aggressive behaviour of prostate cancer. DNA methylation changes between PCa cases with good or poor prognosis (discovery cohort with n = 70) were used as input. DNA was extracted from formalin-fixed tumour tissue, and genome-wide DNA methylation differences between both groups were assessed using Illumina HumanMethylation450 arrays. For the random forest-based modelling, the discovery cohort was randomly split into a training (80%) and a test set (20%). Our methylation-based classifier demonstrated excellent performance in discriminating prognosis subgroups in the test set (Kaplan-Meier survival analyses with log-rank p value < 0.0001). The area under the receiver operating characteristic curve (AUC) for the sensitivity analysis was 95%. Using the ICGC cohort of early- and late-onset prostate cancer (n = 222) and the TCGA PRAD cohort (n = 477) for external validation, AUCs for sensitivity analyses were 77.1% and 68.7%, respectively. Cancer progression-related DNA hypomethylation was frequently located in ‘partially methylated domains’ (PMDs)—large-scale genomic areas with progressive loss of DNA methylation linked to mitotic cell division. We selected several candidate genes with differential methylation in gene promoter regions for additional validation at the protein expression level by immunohistochemistry in > 12,000 tissue micro-arrayed PCa cases. Loss of ZIC2 protein expression was associated with poor prognosis and correlated with significantly shorter time to biochemical recurrence. The prognostic value of ZIC2 proved to be independent from established clinicopathological variables including Gleason grade, tumour stage, nodal stage and prostate-specific-antigen.

Conclusions

Our results highlight the prognostic relevance of methylation loss in PMD regions, as well as of several candidate genes not previously associated with PCa progression. Our robust and externally validated PCa classification model either directly or via protein expression analyses of the identified top-ranked candidate genes will support the clinical management of prostate cancer.
Epigenetic silencing of MEIS2 in prostate cancer recurrence
Authors: Nørgaard Maibritt , Haldrup Christa , Bjerre Marianne Trier , Høyer Søren , Ulhøi Benedicte , Borre Michael , Sørensen Karina D.
Published: October 2019

Background

Current diagnostic and prognostic tools for prostate cancer (PC) are suboptimal, resulting in overdiagnosis and overtreatment of clinically insignificant tumors. Thus, to improve the management of PC, novel biomarkers are urgently needed.

Results

In this study, we integrated genome-wide methylome (Illumina 450K DNA methylation array (450K)) and RNA sequencing (RNAseq) data performed in a discovery set of 27 PC and 15 adjacent normal (AN) prostate tissue samples to identify candidate driver genes involved in PC development and/or progression. We found significant enrichment for homeobox genes among the most aberrantly methylated and transcriptionally dysregulated genes in PC. Specifically, homeobox gene MEIS2 (Myeloid Ecotropic viral Insertion Site 2) was significantly hypermethylated (p < 0.0001, Mann-Whitney test) and transcriptionally downregulated (p < 0.0001, Mann-Whitney test) in PC compared to non-malignant prostate tissue in our discovery sample set, which was also confirmed in an independent validation set including > 500 PC and AN tissue samples in total (TCGA cohort analyzed by 450K and RNAseq). Furthermore, in three independent radical prostatectomy (RP) cohorts (n > 700 patients in total), low MEIS2 transcriptional expression was significantly associated with poor biochemical recurrence (BCR) free survival (p = 0.0084, 0.0001, and 0.0191, respectively; log-rank test). Next, we analyzed another RP cohort consisting of > 200 PC, AN, and benign prostatic hyperplasia (BPH) samples by quantitative methylation-specific PCR (qMSP) and found that MEIS2 was significantly hypermethylated (p < 0.0001, Mann-Whitney test) in PC compared to non-malignant prostate tissue samples (AN and BPH) with an AUC > 0.84. Moreover, in this cohort, aberrant MEIS2 hypermethylation was significantly associated with post-operative BCR (p = 0.0068, log-rank test), which was subsequently confirmed (p = 0.0067; log-rank test) in the independent TCGA validation cohort (497 RP patients; 450K data).

Conclusions

To the best of our knowledge, this is the first study to investigate, demonstrate, and independently validate a prognostic biomarker potential for MEIS2 at the transcriptional expression level and at the DNA methylation level in PC.
A novel real-time intravascular ultrasound double-lumen microcatheter for recanalization of chronic total occlusion: a case report
Authors: Ma Yanzhuo , Peng Yuhong , Wang Gang , Ru Leisheng
Published: October 2019

Background

Chronic total occlusion revascularization remains a challenging problem because of its complexity. We present a case of a patient with chronic total occlusion who was successfully revascularized with the use of a new device called a real-time intravascular ultrasound double-lumen microcatheter.

Case presentation

A 58-year-old East Asians woman presented to our hospital with a complaint of recurrent chest pain of 5 months’ duration. Angiography revealed chronic total occlusion of the right coronary artery from the right coronary artery ostium to the ostia of the posterolateral and posterior descending branches. A guidewire was passed to the distal right coronary artery but went into the false lumens at the posterior descending and posterolateral ostia after use of the antegrade and retrograde approaches. Hence, we used the new device to pass through the subintimal right coronary artery space with reentry into the true lumen before the posterior descending and posterolateral ostia. A stent was successfully deployed at the posterior descending and posterolateral ostia, and the final result was excellent.

Conclusions

This device was useful for finding the entry point and for reentry into the true lumen of a chronic total occlusion. It may be a valuable tool for recanalization of complex chronic total occlusion lesions.
Does co-transplantation of mesenchymal and spermatogonial stem cells improve reproductive efficiency and safety in mice?
Authors: Kadam Prashant , Ntemou Elissavet , Onofre Jaime , Van Saen Dorien , Goossens Ellen
Published: October 2019

Background

Spermatogonial stem cell transplantation (SSCT) is a promising therapy in restoring the fertility of childhood cancer survivors. However, the low efficiency of SSCT is a significant concern. SSCT could be improved by co-transplanting transforming growth factor beta 1 (TGFβ1)-induced mesenchymal stem cells (MSCs). In this study, we investigated the reproductive efficiency and safety of co-transplanting spermatogonial stem cells (SSCs) and TGFβ1-induced MSCs.

Methods

A mouse model for long-term infertility was used to transplant SSCs (SSCT,n = 10) and a combination of SSCs and TGFβ1-treated MSCs (MSi-SSCT,n = 10). Both transplanted groups and a fertile control group (n = 7) were allowed to mate naturally to check the reproductive efficiency after transplantation. Furthermore, the testes from transplanted males and donor-derived male offspring were analyzed for the epigenetic markers DNA methyltransferase 3A (DNMT3A) and histone 4 lysine 5 acetylation (H4K5ac).

Results

The overall tubular fertility index (TFI) after SSCT (76 ± 12) was similar to that after MSi-SSCT (73 ± 14). However, the donor-derived TFI after MSi-SSCT (26 ± 14) was higher compared to the one after SSCT (9 ± 5;P = 0.002), even after injecting half of the number of SSCs in MSi-SSCT. The litter sizes after SSCT (3.7 ± 3.7) and MSi-SSCT (3.7 ± 3.6) were similar but differed significantly with the control group (7.6 ± 1.0;P < 0.001). The number of GFP+offspring per litter obtained after SSCT (1.6 ± 0.5) and MSi-SSCT (2.0 ± 1.0) was also similar. The expression of DNMT3A and H4K5ac in germ cells of transplanted males was found to be significantly reduced compared to the control group. However, in donor-derived offspring, DNMT3A and H4K5ac followed the normal pattern.

Conclusion

Co-transplanting SSCs and TGFβ1-treated MSCs results in reproductive efficiency as good as SSCT, even after transplanting half the number of SSCs. Although transplanted males showed lower expression of DNMT3A and H4K5ac in donor-derived germ cells, the expression was restored to normal levels in germ cells of donor-derived offspring. This procedure could become an efficient method to restore fertility in a clinical setup, but more studies are needed to ensure safety in the long term.
Multi-layer intrusion detection system with ExtraTrees feature selection, extreme learning machine ensemble, and softmax aggregation
Authors: Sharma Jivitesh , Giri Charul , Granmo Ole-Christoffer , Goodwin Morten
Published: October 2019

Recent advances in intrusion detection systems based on machine learning have indeed outperformed other techniques, but struggle with detecting multiple classes of attacks with high accuracy. We propose a method that works in three stages. First, the ExtraTrees classifier is used to select relevant features for each type of attack individually for each (ELM). Then, an ensemble of ELMs is used to detect each type of attack separately. Finally, the results of all ELMs are combined using a softmax layer to refine the results and increase the accuracy further. The intuition behind our system is that multi-class classification is quite difficult compared to binary classification. So, we divide the multi-class problem into multiple binary classifications. We test our method on the UNSW and KDDcup99 datasets. The results clearly show that our proposed method is able to outperform all the other methods, with a high margin. Our system is able to achieve 98.24% and 99.76% accuracy for multi-class classification on the UNSW and KDDcup99 datasets, respectively. Additionally, we use the weighted extreme learning machine to alleviate the problem of imbalance in classification of attacks, which further boosts performance. Lastly, we implement the ensemble of ELMs in parallel using GPUs to perform intrusion detection in real time.
Phylogeny of certain members of Hyrcanus group (Diptera: Culicidae) in China based on mitochondrial genome fragments
Authors: Zhu Hui-Min , Luo Shu-Han , Gao Man , Tao Feng , Gao Jing-Peng , Chen Han-Ming , Li Xiang-Yu , Peng Heng , Ma Ya-Jun
Published: October 2019

Background

Species of theAnopheles hyrcanusgroup are widely distributed in Palearctic and Oriental regions and some of them are important malaria vectors. The cryptic species ofAn. hyrcanusgroup was almost impossible to identify based only on their morphology. The phylogenetic relationship ofAn. hyrcanusgroup was also not clear.

Methods

Five members ofAn. hyrcanusgroup were identified by rDNA ITS2 sequencing asAn. yatsushiroensis, An. belenrae, An. kleini, An. lesteriandAn. sineroides.The mitochondrial genome fragments were sequenced and annotated using the mitochondrial genome ofAn. sinensisas reference. Based on the four segments and Joint Data sequences of these species, and other four anopheline species downloaded from GenBank, intraspecific as well as interspecific genetic distances were calculated and the phylogenetic trees were reconstructed by the methods of neighbor joining, maximum parsimony, minimum evolution and maximum likelihood.

Findings

Four parts of mitochondrial genomes, which were partial fragmentsCOI + tRNA + COII(F5),ATP6 + COIII(F7 + F8),ND1(F19) andlrRNA(F21), were obtained. All fragments were connected as one sequence (referred as Joint Data), which had a total length of 3393 bp. All fragment sequences were highly conservative within species, with the maximumpdistance (0.026) calculated by F19 ofAn. belenrae. The pairwise interspecificpdistance calculated by each fragment showed minor or even no difference amongAn. sinensis,An. kleiniandAn. belenrae. However, interspecificpdistances calculated by the Joint Data sequence ranged from 0.004 (An. belenraevsAn. kleini) to 0.089 (An. sineroidesvsAn. minimus), and thepdistances of the six members ofAn. hyrcanusgroup were all less than 0.029. The phylogenetic tree showed two major clades: all subgenusAnophelesspecies (including six members ofAn. hyrcanusgroup,An. atroparvusandAn. quadrimaculatusA) and subgenusCellia(includingAn. dirusandAn. minimus). TheAn. hyrcanusgroup was divided into two clusters as ((An. lesteri, An. sineroides)An. yatsushiroensis) and ((An. belenrae, An. sinensis)An. kleini)).

Conclusions

TheAn. hyrcanusgroup in this study could be divided into two clusters, in one of whichAn. belenrae, An. sinensisandAn. kleiniwere most closely related. More molecular markers would make greater contribution to phylogenetic analysis.
Isocitrate dehydrogenase inhibitors in acute myeloid leukemia
Authors: Liu Xiaoyan , Gong Yuping
Published: October 2019

Isocitrate dehydrogenase (IDH) is a key enzyme involved in the conversion of isocitrate to α-ketoglutarate (α-KG) in the tricarboxylic acid (TCA) cycle. IDH mutation produces a neomorphic enzyme, which can lead to the abnormal accumulation of R-2-HG and promotes leukemogenesis. IDH mutation occurs in 20% of acute myeloid leukemia (AML) patients, mainly including IDH1 R132, IDH2 R140, and IDH2 R172. Different mutant isoforms have different prognostic values. In recent years, IDH inhibitors have shown good clinical response in AML patients. Hence, enasidenib and ivosidenib, the IDH2 and IDH1 inhibitors developed by Agios Pharmaceuticals, have been approved by the Food and Drug Administration on 1 August 2017 and 20 July 2018 for the treatment of adult relapsed or refractory (R/R) AML with IDH2 and IDH1 mutations, respectively. IDH inhibitor monotherapy for R/R AML is efficacious and safe; however, there are problems, such as primary or acquired resistance. Clinical trials of IDH inhibitors combined with hypomethylating agents or standard chemotherapy for the treatment of R/R AML or newly diagnosed AML, as well as in post hematopoietic stem cell transplantation as maintenance therapy, are ongoing. This article summarizes the use of IDH inhibitors in AML with IDH mutations.
Preferential tau aggregation in von Economo neurons and fork cells in frontotemporal lobar degeneration with specific MAPT variants
Authors: Lin Li-Chun , Nana Alissa L. , Hepker Mackenzie , Hwang Ji-Hye Lee , Gaus Stephanie E. , Spina Salvatore , Cosme Celica G. , Gan Li , Grinberg Lea T. , Geschwind Daniel H. , Coppola Giovanni , Rosen Howard J. , Miller Bruce L. , Seeley William W.
Published: October 2019

Tau aggregation is a hallmark feature in a subset of patients with frontotemporal dementia (FTD). Early and selective loss of von Economo neurons (VENs) and fork cells within the frontoinsular (FI) and anterior cingulate cortices (ACC) is observed in patients with sporadic behavioral variant FTD (bvFTD) due to frontotemporal lobar degeneration (FTLD), including FTLD with tau inclusions (FTLD-tau). Recently, we further showed that these specialized neurons show preferential aggregation of TDP-43 in FTLD-TDP. Whether VENs and fork cells are prone to tau accumulation in FTLD-tau remains unclear, and no previous studies of these neurons have focused on patients with pathogenic variants in the gene encoding microtubule-associated protein tau (FTLD-tau/MAPT). Here, we examined regional profiles of tau aggregation and neurodegeneration in 40 brain regions in 8 patients with FTLD-tau/MAPT and 7 with Pick’s disease (PiD), a sporadic form of FTLD-tau that often presents with bvFTD. We further qualitatively assessed the cellular patterns of frontoinsular tau aggregation in FTLD-tau/MAPT using antibodies specific for tau hyperphosphorylation, acetylation, or conformational change. ACC and mid-insula were among the regions most affected by neurodegeneration and tau aggregation in FTLD-tau/MAPT and PiD. In these two forms of FTLD-tau, severity of regional neurodegeneration and tau protein aggregation were highly correlated across regions. In FTLD-tau/MAPT, VENs and fork cells showed disproportionate tau protein aggregation in patients with V337 M, A152T, and IVS10 + 16 variants, but not in patients with the P301L variant. As seen in FTLD-TDP, our data suggest that VENs and fork cells represent preferentially vulnerable neuron types in most, but not all of the MAPT variants we studied.
Highly sensitive and selective visual detection of Cr(VI) ions based on etching of silver-coated gold nanorods
Authors: Kim Dasom , Choi Eunjin , Lee Chaedong , Choi Yejung , Kim Hoonsub , Yu Taekyung , Piao Yuanzhe
Published: October 2019

We report a visual detection of Cr(VI) ions using silver-coated gold nanorods (AuNR@Ag) as sensing probes. Au NRs were prepared by a seed-mediated growth process and AuNR@Ag nanostructures were synthesized by growing Ag nanoshells on Au NRs. Successful coating of Ag nanoshells on the surface of Au NRs was demonstrated with TEM, EDS, and UV–vis spectrometer. By increasing the overall amount of the deposited Ag on Au NRs, the localized surface plasmon resonance (LSPR) band was significantly blue-shifted, which allowed tuning across the visible spectrum. The sensing mechanism relies on the redox reaction between Cr(VI) ions and Ag nanoshells on Au NRs. As the concentration of Cr(VI) ions increased, more significant red-shift of the longitudinal peak and intensity decrease of the transverse peak could be observed using UV–vis spectrometer. Several parameters such as concentration of CTAB, thickness of the Ag nanoshells and pH of the sample were carefully optimized to determine Cr(VI) ions. Under optimized condition, this method showed a low detection limit of 0.4 μM and high selectivity towards Cr(VI) over other metal ions, and the detection range of Cr(VI) was tuned by controlling thickness of the Ag nanoshells. From multiple evaluations in real sample, it is clear that this method is a promising Cr(VI) ion colorimetric sensor with rapid, sensitive, and selective sensing ability.
Hydrus microstent implantation for surgical management of glaucoma: a review of design, efficacy and safety
Authors: Samet Saba , Ong Jeb A. , Ahmed Iqbal Ike K.
Published: October 2019

With the advent of microinvasive glaucoma surgery (MIGS), the spectrum of modalities available to manage patients with this chronic and heterogeneous condition has broadened. Despite its novelty however, there has been a rapid evolution in the development of a multitude of devices, each targeting a structure along the aqueous drainage pathway. A growing body of evidence has demonstrated IOP and medication burden reduction, and a more favorable safety profile with MIGS procedures in contrast to traditional incisional surgeries. Among the array of MIGS, the Hydrus® Microstent (Ivantis, Inc., Irvine, CA) is a recent FDA approved device, designed to bypass the trabecular meshwork and provide a scaffold for Schlemm’s canal. The objective of this article is to review the Hydrus from conception to clinical use, and present data on its efficacy and safety to date. The available literature has shown promise, however inherent to all novel devices, only long-term monitoring will ensure sustained IOP control and an acceptable safety profile. Surgical advancements in glaucoma have revolutionized the field, and continued research and development will establish these approaches in clinical treatment algorithms.
Using Cultural Historical Activity Theory to understand how emerging technologies can mediate teaching and learning in a mathematics classroom: a review of literature
Authors: Batiibwe Marjorie Sarah Kabuye
Published: October 2019

The purpose of this paper was to review literature on the Cultural Historical Activity Theory (CHAT) and how it has been used to understand the mediation between emerging technologies and teaching and learning in a mathematics classroom. Specifically, it aimed at understanding the genesis of CHAT and further analyzing the studies that have employed CHAT as an analytical framework for teaching and learning in a mathematics classroom context. Two major concerns arise out of this review. Firstly, CHAT has been synonymously used with Activity Theory, leaving one wondering what actually the difference between the two in terms of researchers’ conceptualization is. Secondly, although CHAT has been widely utilized in education research, scholarly articles that have employed it as their theoretical or analytical frameworks in a mathematics classroom context are still too few and yet still, the few that have utilized it have not exploited its maximum potential. The implications for this review for teachers in Uganda are active student engagement and creation of collaboration spaces for dialogue and interaction in the teaching and learning process.
A systematic review of guidelines for managing rheumatoid arthritis
Authors: Mian Aneela , Ibrahim Fowzia , Scott David L.
Published: October 2019

Background

We systematically reviewed current guidelines for managing rheumatoid arthritis (RA) to evaluate their range and nature, assess variations in their recommendations and highlight divergence in their perspectives.

Methods

We searched Medline and Embase databases using the terms ‘clinical practice guidelines’ and ‘rheumatoid arthritis’ from January 2000 to January 2017 together with publications of national and international bodies. We included guidelines providing recommendations on general RA management spanning a range of treatments and published in English. We undertook narrative assessments due to the heterogeneity of the guidelines.

Results

We identified 529 articles; 22 met our inclusion criteria. They were primarily developed by rheumatologists with variable involvement of patient and other experts. Three dealt with early RA, one established RA and 18 all patients. Most guidelines recommend regular assessments based on the Outcome Measures in Rheumatology core dataset; 18 recommended the disease activity score for 28 joints. Twenty recommended targeting remission; 16 suggested low disease activity as alternative. All guidelines recommend treating active RA; 13 made recommendations for moderate disease. The 21 guidelines considering early RA all recommended starting disease modifying drugs (DMARDs) as soon as possible; methotrexate was recommended for most patients. Nineteen recommended combination DMARDs when patients failed to respond fully to monotherapy and biologics were not necessarily indicated. Twenty made recommendations about biologics invariably suggesting their use after failing conventional DMARDs, particularly methotrexate. Most did not make specific recommendations about using one class of biologics preferentially. Eight recommended tapering biologics when patients achieved sustained good responses.

Conclusions

Five general principles transcend most guidelines: DMARDs should be started as soon as possible after the diagnosis; methotrexate is the best initial treatment; disease activity should be regularly monitored; give biologics to patients with persistently active disease who have already received methotrexate; remission or low disease activity are the preferred treatment target.
Insufficient lymph node assessment in gastric adenocarcinoma
Authors: Khanjani Nezhat , Mirzaei Sepideh , Nasrolahi Hamid , Hamedi Seyed Hasan , Mosalaei Ahmad , Omidvari Shapour , Ahmadloo Niloofar , Ansari Mansour , Sobhani Fatemeh , Mohammadianpanah Mohammad
Published: October 2019

Background

This study aimed to investigate the sufficient (≥ 16) lymph node assessment in 449 patients with gastric adenocarcinoma and literature review.

Methods

Four hundred and forty-nine patients with pathologically confirmed locoregional invasive gastric adenocarcinoma from 2004 to 2013 were included. A standard surgical resection was performed for all the patients with (n = 16) or without (n = 433) neoadjuvant treatment.

Results

In this study, 301 men and 148 women with a median age of 58 (range 21–88) years were included. The median total numbers of examined lymph nodes were 9 (range 0–55). Ninety-five patients (21.2%) had adequate (≥ 16) lymph node examination, and 70 patients (15.6%) had no examined lymph nodes. In univariate analysis, total or near total gastrectomy (P <  0.001), advanced node stage (P < 0.001), primary tumor size > 6 cm (P < 0.001), and the presence of perineural invasion (P = 0.039) were associated with more average number of examined lymph nodes. On multivariate analysis, node stage (P < 0.001) and type of surgery (P = 0.008) were independent predictive factors.

Conclusion

In this study, approximately one in five patients with gastric adenocarcinoma had sufficient lymph node assessment. More studies are suggested for identifying a true inadequate lymph node dissection from insufficient lymph node assessment.
PD-1 Blockade in Advanced Adrenocortical Carcinoma
Authors: Raj Nitya , Zheng Youyun , Kelly Virginia , Katz Seth S. , Chou Joanne , Do Richard K.G. , Capanu Marinela , Zamarin Dmitriy , Saltz Leonard B. , Ariyan Charlotte E. , Untch Brian R. , O'Reilly Eileen M. , Gopalan Anuradha , Berger Michael F. , Olino Kelly , Segal Neil H. , Reidy-Lagunes Diane L.
Published: October 2019

PURPOSE

Adrenocortical carcinomas (ACC) are rare and aggressive malignancies with limited treatment options. This study was undertaken to evaluate the immunogenicity of ACC.

PATIENTS AND METHODS

Patients with advanced ACC were enrolled in a phase II study to evaluate the clinical activity of pembrolizumab 200 mg every 3 weeks, without restriction on prior therapy. The primary end point was objective response rate. Efficacy was correlated with tumor programmed death-ligand 1 expression, microsatellite-high and/or mismatch repair deficient (MSI-H/MMR-D) status, and somatic and germline genomic correlates.

RESULTS

We enrolled 39 patients with advanced ACC and herein report after a median follow-up of 17.8 months (range, 5.4 months to 34.7 months). The objective response rate to pembrolizumab was 23% (nine patients; 95% CI, 11% to 39%), and the disease control rate was 52% (16 patients; 95% CI, 33% to 69%). The median duration of response was not reached (lower 95% CI, 4.1 months). Two of six patients with MSI-H/MMR-D tumors responded. The other seven patients with objective responses had microsatellite stable tumors. The median progression-free survival was 2.1 months (95% CI, 2.0 months to 10.7 months), and the median overall survival was 24.9 months (95% CI, 4.2 months to not reached). Thirteen percent of patients (n = 5) had treatment-related grade 3 or 4 adverse events. Tumor programmed death-ligand 1 expression and MSI-H/MMR-D status were not associated with objective response.

CONCLUSION

MSI-H/MMR-D tumors, for which pembrolizumab is a standard therapy, are more common in ACC than has been recognized. In advanced ACC that is microsatellite stable, pembrolizumab provided clinically meaningful and durable antitumor activity with a manageable safety profile.
Outcomes in Patients With Pancreatic Adenocarcinoma With Genetic Mutations in DNA Damage Response Pathways: Results From the Know Your Tumor Program
Authors: Pishvaian Michael J. , Blais Edik M. , Brody Jonathan R. , Rahib Lola , Lyons Emily , De Arbeloa Patricia , Hendifar Andrew , Mikhail Sameh , Chung Vincent , Sohal Davendra P.S. , Leslie Sam , Mason Kimberly , Tibbets Lisa , Madhavan Subha , Matrisian Lynn M. , Petricoin Emanuel
Published: October 2019

PURPOSE

Up to 25% of pancreatic adenocarcinomas (PDACs) harbor mutations in the homologous recombination DNA damage response (HR-DDR) pathway. Although known to affect responsiveness to DNA-damaging chemotherapy, the prognostic relevance of these mutations is unclear and outcomes in patients with PDAC who harbor HR-DDR mutations beyond BRCA1/2 remain unexplored.

METHODS

We evaluated 820 patients with PDAC enrolled in the Know Your Tumor program for whom we had collected comprehensive genomic testing results and longitudinal clinical outcomes. Patients were categorized as having resected versus advanced disease, and as having received platinum-based therapy versus being platinum naïve. Tumor genomic profiles were categorized as HR-DDR mutated (HR-DDRmut) or proficient (pHR-DDR) on the basis of the presence of pathogenic mutations of somatic or germline origin in BRCA1/2 or PALB2 (group 1); ATM/ATR/ATRX (group 2); or BAP1, BARD1, BRIP1, CHEK1/2, RAD50/51/51B, or FANCA/C/D2/E/F/G/L (group 3). Overall survival was measured from the date of diagnosis until death.

RESULTS

Median overall survival (mOS) was similar in all resected patients irrespective of exposure to platinum-based therapy, whereas for platinum-treated patients with advanced disease, mOS was significantly longer for HR-DDRmut versus pHR-DDR (2.37 years v 1.45 years, respectively). Of importance, no difference was identified in platinum-naïve patients. mOS in patients with mutations in all three HR-DDRmut groups was greater than that for pHR-DDR patients, but this difference was lost in platinum-naïve patients.

CONCLUSION

Patients with advanced HR-DDRmut have improved mOS when treated with platinum-based therapy compared with pHR-DDR patients. In platinum-naïve patients, there is no mOS difference, which suggests that HR-DDR status has no pure prognostic value. These findings support the need to test all patients with advanced PDAC to ensure that HR-DDRmut patients receive the benefit of treatment with platinum-based therapy.
Diagnostic Laparoscopy as a Selection Tool for Patients with Colorectal Peritoneal Metastases to Prevent a Non-therapeutic Laparotomy During Cytoreductive Surgery
Authors: Hentzen Judith E. K. R. , Constansia Reickly D. N. , Been Lukas B. , Hoogwater Frederik J. H. , van Ginkel Robert J. , van Dam Gooitzen M. , Hemmer Patrick H. J. , Kruijff Schelto
Published: October 2019

Objective

The aim of this study was to evaluate the introduction of diagnostic laparoscopy (DLS) in patients with colorectal peritoneal metastases (PM) to prevent non-therapeutic laparotomies during cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS + HIPEC).

Methods

Patients with histologically proven colorectal PM who underwent a laparotomy for potential CRS + HIPEC from January 2006 to January 2019 were retrospectively identified from a prospectively maintained database. In 2012, DLS was introduced in the preoperative work-up for CRS + HIPEC in our academic center. The rates of non-therapeutic laparotomies, major postoperative complications (Clavien–Dindo grade III or higher), and survival outcomes were investigated for patients who underwent a laparotomy before (cohort A) and after (cohort B) the introduction of DLS. In cohort B, the reasons to refrain from DLS were retrospectively explored from medical records.

Results

Overall, 172 patients were included [cohort A: 48 patients (27.9%); cohort B: 124 patients (72.1%)]. A significant drop in the rate of non-therapeutic laparotomies occurred in cohort B compared with cohort A (21.0 vs. 35.4%: p = 0.044), despite only 85 patients (68.5%) from cohort B undergoing DLS in our academic center. The most important reason to refrain from DLS was a recently performed DLS or laparotomy in the referring hospital (48.7%). Major postoperative complications, in-hospital mortality, and survival outcomes were similar for both cohorts.

Conclusions

Performing DLS during the preoperative work-up for CRS + HIPEC prevents non-therapeutic laparotomies in patients with colorectal PM. We recommend performing this laparoscopic screening in an experienced HIPEC center.
HOUSTON, WE HAVE A (PHYSICAL ACTIVITY) PROBLEM
Authors: Peterman James E. , Bassett David R.
Published: October 2019

Apply It!Summary Statement:Pulled Text:

• Physical activity is associated with several health and well-being benefits, but current levels of daily physical activity are at an all-time low.

• Daily physical activity has decreased over the years due to declining lifestyle physical activity levels.

• Innovative strategies from health and fitness professionals are needed to promote physical activity throughout the day.

Physical activity is associated with several health and well-being benefits but has decreased over the years due to declining rates of lifestyle physical activity.

“Despite these well-known benefits of physical activity though, there has still been a gradual decline in overall daily physical activity levels.”

“Various devices/appliances have been invented that reduce the physical activity associated with performing household chores. For example, sweeping requires moderate-intensity physical activity but can now be replaced with an autonomous robotic vacuum cleaner (e.g., the ‘Roomba’).”

Performing these tasks without modern technology, Amish adults accumulate an average of 48 hours per week of moderate- to vigorous-intensity physical activity (14).
Real right
Authors: Формакидов Дмитрий , Formakidov Dmitriy
Published: October 2019

The textbook introduces the reader to the problems of modern Russian legislative regulation of real rights in General and each real right in particular, the prospects for the development of Russian legislation on real rights. It formulated General methodological requirements students in the study of the course "Property law", highlights the policy issues of the course are given a list of educational, monographic, periodical literature, legal acts and court practice, which are recommended for the assimilation of the main provisions, and in-depth study of this discipline. Prepared taking into account the latest acts of the Russian legislation and practice of its application.
Meets the requirements of the Federal state educational standards of higher education of the last generation.
For teachers and students of law faculties and all who are interested in problems of real legal relations. It is intended for directions of preparation 40.03.01 and 40.04.01 "Jurisprudence".
The Problem of the Formation of Recreational Imagination by Primary School Readers
Authors: Сильченкова Л. , Sil'chenkova L. , Страдова А. , Stradova A.
Published: October 2019

The article is devoted to the urgent problem of modern primary education - the formation of recreating imagination by schoolchildren as an essential prerequisite and a necessary component of reading literacy. Imagination is considered as a synthesis of ideas, thinking, memory, attention, intuition during the perception of the text. It completes this synthesis. Taking into account the conclusions of specialists in the field of psychology and great pedagogical experience, the examples and the work of schoolchildren with literary and artistic works reveal the possibilities and conditions for the formation of their readers’ recreational imagination in the educational practice of elementary schools.
Formation of Social and Communicative Skills of Primary School Students During the Implementation of the Extracurricular Activities Program
Authors: Байбакова О. , Baybakova O. , Журавлева С. , Zhuravleva S.
Published: October 2019

The article discusses the theoretical foundations of the problem of socio-communicative development of primary school children, the formation of their communicative universal educational actions. The pedagogical possibilities of the program of social and communicative development of primary school students in extracurricular activities are revealed. The goals, objectives and structure of the author’s program “We live in the world”, the mechanisms, forms, methods of its implementation in primary education are described. The results of a study of the ecopsychological types of interaction between a primary school student in the “man – educational environment” system and the formation of his subjective position in the process of communication with peers are presented.
A Bilevel Model for Network Design and Pricing Based on a Level-of-Service Assessment
Authors: Tawfik Christine , Limbourg Sabine
Published: October 2019

Within a wide view to stimulate intermodal transport, this paper is devoted to the examination of the intrinsically related problems of designing freight carrying services and determining their associated prices as observed by the shipper firms. A path-based multicommodity formulation is developed for a medium-term planning horizon, from the perspective of an intermodal operator. In the quest of incorporating nonprice attributes, two approaches are proposed to depict a realistic assessment of the service quality. First, frequency delay constraints are added to the upper-level problem. Second, based on a random utility model, behavioral concepts are integrated in the expression of the lower level as a logistics costs minimization problem. Exact tests are invoked on real-world instances, demonstrating the capability of the presented approaches of reaching reasonable results within acceptable computation times and optimality gaps. The broader level-of-service perspective imposes additional costs on the service providers, although to a lesser extent on long-distance freight corridors, as indicated by the computed market share and net profit. Further experiments are conducted to test the impact of certain transport management instruments (e.g., subsidies and service capacities) on the modal split, as well as to assess the intermodality’s future based on a scenario analysis methodology.
Model-Based Prediction of Dissolved Oxygen Content in Fish Production
Authors: Zhu Nanyang , Xia Qian , Tan Jinglu , Jiang Yongnian , Xu Guanhua , Chu Dan , Guo Ya
Published: October 2019

Dissolved oxygen (DO) plays a vital role in fish production, but DO sensors are expensive and often malfunction as a result of corrosion and deposition of debris. In this work, polynomial regression, back-propagation neural network (BPNN), and long short-term memory (LSTM) were applied to develop models for estimation of DO from non-DO measurements in fish production. The root mean square error (RMSE), mean absolute percentage error (MAPE), coefficient of determination (R2), index of agreement (d), and Nash-Sutcliffe efficiency coefficient (NSE) were used to measure the performance of the three models. The results showed that the LSTM model achieved the best performance. A trained LSTM model can be used to estimate DO from water pH, temperature, and turbidity without using DO sensors. The estimated DO values can be used as a warning signal for DO sensor maintenance and as estimates of compromised DO measurements in fish production.

Highlights

Prediction models were developed to estimate dissolved oxygen (DO) and their performance.

The LSTM model achieved the best performance and can be used to estimate DO without using DO sensors.

The estimated DO can be used as a warning signal for DO sensor malfunction and maintenance.

The estimated DO can also be used to correct compromised DO measurements.

Keywords: BP neural network, Dissolved oxygen, Long short-term memory, Polynomial regression, Principal component analysis.
Análise Swot: Um Estudo sobre o Nível de Competitividade de uma Empresa de Fast-Food Japonês
Authors: Mirales Elisa , Jacomino Gabriela Porfírio , Baldin Célia
Published: October 2019

Este estudo trata sobre competitividade no contexto empresarial. Objetivou-se analisar o nível de competitividade, por meio da matriz SWOT, de um restaurante de fast-food japonês. Trata-se de uma pesquisa de natureza qualitativa, por meio de um estudo de caso, com dados coletados por meio de entrevista e analisados por meio de técnicas de análise de conteúdo. Resultados demonstram que o restaurante pode atingir um nível de competitividade mais elevado, uma vez que todas os fatores analisados foram avaliados como pontos fortes (internamente) e oportunidades (externamente). Identificou-se, ainda, que a empresa tem capacidade para evoluir em tais aspectos, dispondo dos recursos necessários para competir com destaque no mercado local.
Voluntary sector responses to food poverty: responding in the short term and working for longer-term change
Authors: Denning Stephanie
Published: October 2019

In this paper I respond to the question of whether voluntary sector responses to food poverty in the UK are a sticking plaster without addressing the causes of food poverty. I do so by drawing on a case study of a holiday hunger project and I reflect on three principles: being relational,
encouraging participation and working for justice. I conclude with three recommendations for how voluntary sector organisations can work towards both short- and longer-term responses to food poverty.
The Whole Place Self: reflecting on the original working practices of Rape Crisis
Authors: Vera-Gray F.
Published: October 2019

Critiques of the trauma model for understanding the harms of sexual violence raise some important questions about the radical roots of Rape Crisis Centres in the UK and their relationship to the services offered, and funded, today. Drawing from a research conversation with three women from the national umbrella group Rape Crisis England and Wales, this article finds that in contrast to the depoliticised and individualised discourse of trauma, the original ethos of Rape Crisis in England sought to recognise the harms of rape across four interlocking dimensions: personal, cultural, social and structural. This approach demonstrates an understanding of the self as relational, situated and intersectional, aligning with recent philosophical work on sexual violence and suggesting the importance of key working practices that are in tension with the counselling model that currently dominates provision.