bluuebunny/crossref_metadata_2025 huggingface dataset:
Cisplatin treatment of testicular cancer patients introduces long-term changes in the epigenome
Authors: Bucher-Johannessen Cecilie , Page Christian M. , Haugen Trine B. , Wojewodzic Marcin W. , Fosså Sophie D. , Grotmol Tom , Haugnes Hege S. , Rounge Trine B.
Published: December 2019

Background

Cisplatin-based chemotherapy (CBCT) is part of standard treatment of several cancers. In testicular cancer (TC) survivors, an increased risk of developing metabolic syndrome (MetS) is observed. In this epigenome-wide association study, we investigated if CBCT relates to epigenetic changes (DNA methylation) and if epigenetic changes render individuals susceptible for developing MetS later in life. We analyzed methylation profiles, using the MethylationEPIC BeadChip, in samples collected ~ 16 years after treatment from 279 Norwegian TC survivors with known MetS status. Among the CBCT treated (n= 176) and non-treated (n= 103), 61 and 34 developed MetS, respectively. We used two linear regression models to identify if (i) CBCT results in epigenetic changes and (ii) epigenetic changes play a role in development of MetS. Then we investigated if these changes in (i) and (ii) links to genes, functional networks, and pathways related to MetS symptoms.

Results

We identified 35 sites that were differentially methylated when comparing CBCT treated and untreated TC survivors. The PTK6–RAS–MAPk pathway was significantly enriched with these sites and infers a gene network of 13 genes withCACNA1D(involved in insulin release) as a network hub.We found nominal MetS-associations and a functional gene network withABCG1andNCF2as network hubs.

Conclusion

Our results suggest that CBCT has long-term effects on the epigenome. We could not directly link the CBCT effects to the risk of developing MetS. Nevertheless, since we identified differential methylation occurring in genes associated with conditions pertaining to MetS, we hypothesize that epigenomic changes may also play a role in the development of MetS in TC survivors. Further studies are needed to validate this hypothesis.
A de novo molecular generation method using latent vector based generative adversarial network
Authors: Prykhodko Oleksii , Johansson Simon Viet , Kotsias Panagiotis-Christos , Arús-Pous Josep , Bjerrum Esben Jannik , Engkvist Ola , Chen Hongming
Published: December 2019

Deep learning methods applied to drug discovery have been used to generate novel structures. In this study, we propose a new deep learning architecture, LatentGAN, which combines an autoencoder and a generative adversarial neural network for de novo molecular design. We applied the method in two scenarios: one to generate random drug-like compounds and another to generate target-biased compounds. Our results show that the method works well in both cases. Sampled compounds from the trained model can largely occupy the same chemical space as the training set and also generate a substantial fraction of novel compounds. Moreover, the drug-likeness score of compounds sampled from LatentGAN is also similar to that of the training set. Lastly, generated compounds differ from those obtained with a Recurrent Neural Network-based generative model approach, indicating that both methods can be used complementarily.
IgM-enriched immunoglobulins (Pentaglobin) may improve the microcirculation in sepsis: a pilot randomized trial
Authors: Domizi Roberta , Adrario Erica , Damiani Elisa , Scorcella Claudia , Carsetti Andrea , Giaccaglia Paolo , Casarotta Erika , Gabbanelli Vincenzo , Pantanetti Simona , Lamura Elena , Ciucani Silvia , Donati Abele
Published: December 2019

Background

Polyclonal or IgM-enriched immunoglobulins may be beneficial during sepsis as an adjuvant immunomodulatory therapy. We aimed to test whether the infusion of IgM-enriched immunoglobulins improves microvascular perfusion during sepsis.

Methods

Single-centre, randomized, double-blind, placebo-controlled phase II trial including adult patients with a diagnosis of sepsis or septic shock for less than 24 h. Patients received an intravenous infusion of 250 mg/kg (5 mL/kg) per day of IgM-enriched immunoglobulins (Pentaglobin, n = 10) for 72 h or placebo (NaCl 0.9%, n = 9). At baseline and after 24 and 72 h of infusion, the sublingual microcirculation was assessed with Incident Dark Field videomicroscopy. Thenar near-infrared spectroscopy (NIRS) was applied with a vascular occlusion test to assess tissue oxygenation and microvascular reactivity. Levels of interleukin (IL) 1-beta, IL-6, IL-8, IL-10 and tumour necrosis factor alpha were measured in the serum.

Results

The perfused vessel density (PVD) for small vessels (diameter < 20 micron) increased in the Pentaglobin group (from 21.7 ± 4.7 to 25.5 ± 5.1 mm/mm2) and decreased in the placebo group (from 25 ± 5.8 to 20.7 ± 4.1 mm/mm2, p for interaction < 0.001, two-way analysis of variance). The absolute between-group difference at 72 h was 4.77 (standard error 2.34), p = 0.140. The microvascular flow index for small vessels increased at 24 h in the Pentaglobin group (from 2.68 [2.38–2.78] to 2.93 [2.82–3], p < 0.01) and decreased at 72 h in the placebo group (from 2.83 [2.60–2.97] to 2.67 [2.48–2.73], p < 0.05). Changes in general parameters, cytokines and NIRS-derived parameters were similar between the two groups, except for IL-6 and IL-10 that significantly decreased at 72 h only in the Pentaglobin group.

Conclusions

A 72-h infusion of IgM-enriched immunoglobulins (Pentaglobin) in patients with sepsis or septic shock may be associated with an increase in sublingual microvascular perfusion. Further studies are needed to confirm our findings.

Trial registration NCT02655133, www.ClinicalTrials.gov, date of registration 7th January 2016, https://www.clinicaltrials.gov/ct2/show/NCT02655133.
Clinical outcomes of hospitalised patients with catheter-associated urinary tract infection in countries with a high rate of multidrug-resistance: the COMBACTE-MAGNET RESCUING study
Authors:   on behalf of RESCUING Study Group and Study Sites, Gomila Aina , Carratalà Jordi , Eliakim-Raz Noa , Shaw Evelyn , Tebé Cristian , Wolkewitz Martin , Wiegand Irith , Grier Sally , Vank Christiane , Cuperus Nienke , Van den Heuvel Leonard , Vuong Cuong , MacGowan Alasdair , Leibovici Leonard , Addy Ibironke , Pujol Miquel
Published: December 2019

Background

Although catheter-associated urinary tract infection (CA-UTI) is a major healthcare-related problem worldwide, there is a scarcity of current data from countries with high antimicrobial resistance rates. We aimed to determine the clinical outcomes of patients with CA-UTI compared to those of patients with other sources of complicated urinary tract infection (cUTI), and to assess the impact of antimicrobial resistance. We also aimed to identify the factors influencing 30-day mortality among patients with CA-UTI.

Methods

This was a multicentre, multinational retrospective cohort study including hospitalised adults with cUTI between January 2013 and December 2014 in twenty hospitals from eight countries from southern Europe, Turkey and Israel. The primary endpoint was 30-day mortality. The secondary endpoints were length of hospital stay, symptom improvement after 7 days’ treatment, symptom recurrence at 30 days and readmission 60 days after hospital discharge.

Results

Of the 807 cUTI episodes, 341 (42.2%) were CA-UTIs. The time from catheter insertion to cUTI diagnosis was less than 2 weeks in 44.6% of cases. Overall, 74.5% of cases had hospital or healthcare-acquired CA-UTI. Compared to patients with other cUTI aetiologies, those with CA-UTI had the following characteristics: they were more frequently males, older, admitted for a reason other than cUTI and admitted from a long-term care facility; had higher Charlson’s comorbidity index; and more frequently had polymicrobial infections and multidrug-resistant Gram-negative bacteria (MDR-GNB). Patients with CA-UTI also had significantly higher 30-day mortality rates (15.2% vs 6%) and longer hospital stay (median 14 [interquartile range -IQR- 7-27] days vs 8 [IQR 5–14] days) than patients with cUTI of other sources. After adjusting for confounders, CA-UTI was not independently associated with an increased risk of mortality (odds ratio, 1.40; 95% confidence interval, 0.77–2.54), and neither was the presence of MDR-GNB.

Conclusions

CA-UTI was the most frequent source of cUTI, affecting mainly frail patients. The mortality of patients with CA-UTI was high, though this was not directly related to the infection.
High insecticide resistance in the major malaria vector Anopheles coluzzii in Chad Republic
Authors: Ibrahim Sulaiman S. , Fadel Amen N. , Tchouakui Magellan , Terence Ebai , Wondji Murielle J. , Tchoupo Micareme , Kérah-Hinzoumbé Clement , Wanji Samuel , Wondji Charles S.
Published: December 2019

Background

The Sahel region of Chad Republic is a prime candidate for malaria pre-elimination. To facilitate pre-elimination efforts in this region, two populations ofAnopheles coluzziifrom Central Chad Republic were characterized, their insecticide resistance profile and the possible molecular mechanisms driving the resistance in the field investigated.

Methods

Bloodfed femaleAnopheles gambiaes.l. resting indoor, were collected at N’djamena and Massakory, Chad in 2018 and characterized for species composition, and infection rate was determined using the TaqMan assay. Susceptibility to various insecticides was assessed using WHO tube bioassays. Cone bioassays were conducted using various long-lasting insecticidal nets (LLINs). Results were analysed using Chi Square test. Knockdown resistance (kdr) andace-1markers were investigated by TaqMan genotyping.

Results

Anopheles coluzziiwas the major vector found in N’djamena (100%) and Massakory (~ 94%). NoPlasmodiumwas found in 147 bloodfed F0An. coluzzii(82 from N’djamena and 65 from Massakory).High intensity pyrethroid resistance was observed with mortalities of < 2% for permethrin, deltamethrin and etofenprox, and with < 50% and < 60% dead following exposure to 10× diagnostic doses of deltamethrin and permethrin, respectively. For both sites, < 10% mortalities were observed with DDT. Synergist bioassays with piperonylbutoxide significantly recovered pyrethroid susceptibility in Massakory populations, implicating CYP450s (mortality = 13.6% for permethrin,χ2 = 22.8, df = 1,P = 0.0006; mortality = 13.0% for deltamethrin,χ2 = 8.8, df = 1,P < 0.00031). Cone-bioassays established complete loss of efficacy of the pyrethroid-based LLINs; and a 100% recovery of susceptibility following exposure to the roof of PermaNet®3.0, containing piperonylbutoxide. Both populations were susceptible to malathion, but high bendiocarb resistance was observed in Massakory population. The absence oface-1mutation points to the role of metabolic resistance in the bendiocarb resistance. Both 1014F and 1014S mutations were found in both populations at around 60% and < 20% respectively. Sequencing of intron-1 of the voltage-gated sodium channel revealed a low genetic diversity suggesting reduced polymorphism.

Conclusions

Multiple resistance inAn. coluzziipopulations from Chad highlight challenges associated with deployment of LLINs and indoor residual spraying (IRS) in the Sahel of this country. The pyrethroid-synergists LLINs (e.g. PermaNet®3.0) and organophosphate-based IRS maybe the alternatives for malaria control in this region.
Luminescent conjugated oligothiophenes distinguish between α-synuclein assemblies of Parkinson’s disease and multiple system atrophy
Authors: Klingstedt Therése , Ghetti Bernardino , Holton Janice L. , Ling Helen , Nilsson K. Peter R. , Goedert Michel
Published: December 2019

Synucleinopathies [Parkinson’s disease with or without dementia, dementia with Lewy bodies and multiple system atrophy] are neurodegenerative diseases that are defined by the presence of filamentous α-synuclein inclusions. We investigated the ability of luminescent conjugated oligothiophenes to stain the inclusions of Parkinson’s disease and multiple system atrophy. They stained the Lewy pathology of Parkinson’s disease and the glial cytoplasmic inclusions of multiple system atrophy. Spectral analysis of HS-68-stained inclusions showed a red shift in multiple system atrophy, but the difference with Parkinson’s disease was not significant. However, when inclusions were double-labelled for HS-68 and an antibody specific for α-synuclein phosphorylated at S129, they could be distinguished based on colour shifts with blue designated for Parkinson’s disease and red for multiple system atrophy. The inclusions of Parkinson’s disease and multiple system atrophy could also be distinguished using fluorescence lifetime imaging. These findings are consistent with the presence of distinct conformers of assembled α-synuclein in Parkinson’s disease and multiple system atrophy.
The amyloid-β degradation intermediate Aβ34 is pericyte-associated and reduced in brain capillaries of patients with Alzheimer’s disease
Authors: Kirabali Tunahan , Rigotti Serena , Siccoli Alessandro , Liebsch Filip , Shobo Adeola , Hock Christoph , Nitsch Roger M. , Multhaup Gerhard , Kulic Luka
Published: December 2019

An impairment of amyloid β-peptide (Aβ) clearance is suggested to play a key role in the pathogenesis of sporadic Alzheimer’s disease (AD). Amyloid degradation is mediated by various mechanisms including fragmentation by enzymes like neprilysin, matrix metalloproteinases (MMPs) and a recently identified amyloidolytic activity of β-site amyloid precursor protein cleaving enzyme 1 (BACE1). BACE1 cleavage of Aβ40 and Aβ42 results in the formation of a common Aβ34 intermediate which was found elevated in cerebrospinal fluid levels of patients at the earliest disease stages. To further investigate the role of Aβ34 as a marker for amyloid clearance in AD, we performed a systematic and comprehensive analysis of Aβ34 immunoreactivity in hippocampal and cortical post-mortem brain tissue from AD patients and non-demented elderly individuals. In early Braak stages, Aβ34 was predominantly detectable in a subset of brain capillaries associated with pericytes, while in later disease stages, in clinically diagnosed AD, this pericyte-associated Aβ34 immunoreactivity was largely lost. Aβ34 was also detected in isolated human cortical microvessels associated with brain pericytes and its levels correlated with Aβ40, but not with Aβ42 levels. Moreover, a significantly decreased Aβ34/Aβ40 ratio was observed in microvessels from AD patients in comparison to non-demented controls suggesting a reduced proteolytic degradation of Aβ40 to Aβ34 in AD. In line with the hypothesis that pericytes at the neurovascular unit are major producers of Aβ34, biochemical studies in cultured human primary pericytes revealed a time and dose dependent increase of Aβ34 levels upon treatment with recombinant Aβ40 peptides while Aβ34 production was impaired when Aβ40 uptake was reduced or BACE1 activity was inhibited. Collectively, our findings indicate that Aβ34 is generated by a novel BACE1-mediated Aβ clearance pathway in pericytes of brain capillaries. As amyloid clearance is significantly reduced in AD, impairment of this pathway might be a major driver of the pathogenesis in sporadic AD.
The synthesis characterization of historical novel azo pigments: implications for conservation science
Authors: Lomax Suzanne Quillen , Lomax Joseph F.
Published: December 2019

A series of synthetic organic pigments (SOP’s) with azo-containing linkages have been synthesized and characterized by Fourier transform infrared (FTIR) and Raman spectroscopies and laser desorption ionization mass spectrometry (LDI-MS). These pigments include representatives of the chemical classes arylide (Hansa) yellow, diarylide yellow and oranges, and Naphthol AS. Certain of these (PR7, PR10, PR11, PR18, PR19, PO14, PO15, PO16, PY49, PY98, PY106, PY113, PY124, PY203) are historical pigments, that is they were manufactured but subsequently were removed from production. Of these, some have been brought back into limited production. In addition to the above-mentioned pigments, 18 products of azo-linkage reactions formed between N,N′-bis(acetoacetyl)-o-toluidine and substituted anilines have been synthesized and characterized by the methods listed above as well as by visible reflectance spectroscopy. While not commercially available azo pigments, these colorants will serve as model systems to study substituent effects on pigment color.
Fault weakening caused by smectite swelling
Authors: Kameda Jun , Uno Masaoki , Conin Marianne , Ujiie Kohtaro , Hamada Yohei , Kimura Gaku
Published: December 2019

The large slip along the shallow subduction interface during the 2011 Tohoku-Oki earthquake (Mw9.0) caused a huge tsunami that struck the northeast coast of Honshu, Japan. The Integrated Ocean Drilling Program Expedition 343 JFAST program revealed that the fault zone is composed primarily of smectite. Our swelling experiments using the fault material demonstrated that the swelling pressure systematically increases with a decrease in sample porosity. Based on in situ porosity estimations in the IODP borehole, the swelling pressure of the fault is as high as 8 MPa, which is comparable to the effective normal stress at the drill site (~ 7 MPa). This also suggests that the modified effective confining pressure of the fault is quite low or potentially zero, meaning that fault strength is governed mainly by cohesion rather than frictional strength. The fault may therefore be intrinsically weak, which could enhance the coseismic displacement toward the trench when earthquake slip propagates from depth.
Magnetic dating of the Holocene monogenetic Tkarsheti volcano in the Kazbeki region (Great Caucasus)
Authors: Vashakidze Goga , Goguitchaichvili Avto , García-Redondo Natalia , Calvo-Rathert Manuel , Carrancho Ángel , Cejudo Ruben , Morales Juan , Lebedev Vladimir A. , Gabarashvili Ketino
Published: December 2019

The radiocarbon technique is widely used to date Late Pleistocene and Holocene lava flows. The significant difference with palaeomagnetic methods is that the 14C dating is performed on the organic matter carbonized by the rock formation or the paleosols found within or below the lava flow. On the contrary, the archaeomagnetic dating allows to date the moment when the lava is cooling down below the Curie temperatures. In the present study, we use the paleomagnetic dating to constrain the age of the Tkarsheti monogenetic volcano located within the Kazbeki Volcanic Province (Great Caucasus). A series of rock-magnetic experiments including the measurement of hysteresis curves, isothermal remanence, back-field and continuous thermomagnetic curves were applied. These experiments indicated that Pseudo-Single-Domain Ti-poor titanomagnetite is responsible for remanence. A characteristic remanent magnetization was obtained for all twenty analyzed samples yielding a stable single magnetization component observed upon both thermal and alternating field treatments. Comparison of the mean directions obtained (Inc = 48.6º, Dec = 6.4º, A95 = 4.0° and K = 67) with the SCHA.DIF.14k model yielded two main time intervals (4740–4650 or 4427–4188 BC) as the best age estimate of the Lesser Tkarsheti lava flow. These results suggest an earlier age (between approximately 200 and 700 years) for this monogenetic lava flow than expected from the estimated age provided by a former 14C dating obtained in 1973 on woody remains. This first attempt to use the archaeomagnetic technique in the Caucasus indicates that the SCHA.DIF.14k geomagnetic model may be successfully used for dating purposes in the region .
Tumor-specific delivery of KRAS siRNA with iRGD-exosomes efficiently inhibits tumor growth
Authors: Zhou Yu , Yuan Yuan , Liu Minghui , Hu Xiuting , Quan Yiming , Chen Xi
Published: December 2019

Lung cancer is the major cause of cancer-related deaths globally. Mutant KRAS is a feature of 15–50% of lung cancer cases and represents one of the most prevalent oncogenic drivers in this disease. Unfortunately, although much effort has been spent on searching for small molecule inhibitors of KRAS, KRAS gene has proven extraordinarily difficult to target by current pharmacological agents. In the present study, we developed an alternative strategy to silence the so-called untargetable and undruggable KRAS gene by employing exosome-mediated siRNA delivery. Particularly, we reprogrammed HEK293T cells to simultaneously express KRAS siRNA and Lamp2b, an exosomal membrane protein, in fusion with a tumor-penetrating internalizing RGD (iRGD) peptide (CRGDKGPDC), and then purified the tumor-targeting exosomes as KRAS siRNA delivery system. In agreement with the study design, intravenously injected iRGD-exosomes specifically targeted to tumor tissues in vivo. The therapeutic potential was revealed by the strong inhibition of tumor growth in a mouse model after intravenous injection of KRAS siRNA encapsulated in iRGD-exosomes. In conclusion, our results indicate that iRGD-tagged exosomes is an ideal delivery agent to transport KRAS siRNAs for lung cancer treatment. As an extension of this finding, the vast majority of mutated genes that are difficult to target by current pharmacological agents will be targetable and druggable in the future.
The problem with skeletal muscle series elasticity
Authors: Herzog Walter
Published: December 2019

Muscles contain contractile and (visco-) elastic passive components. At the latest since Hill’s classic works in the 1930s, it has been known that these elastic components affect the length and rate of change in length of the contractile component, and thus the active force capability of dynamically working muscles. In an attempt to elucidate functional properties of these muscle elastic components, scientists have introduced the notion of “series” and “parallel” elasticity. Unfortunately, this has led to much confusion and erroneous interpretations of results when the mechanical definitions of parallel and series elasticity were violated.

In this review, I will focus on muscle series elasticity, by first providing the mechanical definition for series elasticity, and then provide theoretical and experimental examples of the concept of series elasticity. Of particular importance is the treatment of aponeuroses. Aponeuroses are not in series with the tendon of a muscle nor the muscle’s contractile elements. The implicit and explicit treatment of aponeuroses as series elastic elements in muscle has led to incorrect conclusions about aponeuroses stiffness and Young’s modulus, and has contributed to vast overestimations of the storage and release of mechanical energy in cyclic muscle contractions.

Series elasticity is a defined mechanical concept that needs to be treated carefully when applied to skeletal muscle mechanics. Measuring aponeuroses mechanical properties in a muscle, and its possible contribution to the storage and release of mechanical energy is not trivial, and to my best knowledge, has not been (correctly) done yet.
Optimising treatment decision rules through generated effect modifiers: a precision medicine tutorial
Authors: Petkova Eva , Park Hyung , Ciarleglio Adam , Todd Ogden R. , Tarpey Thaddeus
Published: December 2019

This tutorial introduces recent developments in precision medicine for estimating treatment decision rules. The objective of these developments is to advance personalised healthcare by identifying an optimal treatment option for each individual patient based on each patient's characteristics. The methods detailed in this tutorial define composite variables from the patient measures that can be viewed as ‘biosignatures’ for differential treatment response, which we have termed ‘generated effect modifiers’. In contrast to most machine learning approaches to precision medicine, these biosignatures are derived from linear and non-linear regression models and thus have the advantage of easy visualisation and ready interpretation. The methods are illustrated using examples from randomised clinical trials.
Myotonic Muscular Dystrophies
Authors: Johnson Nicholas E.
Published: December 2019

PURPOSE OF REVIEW

This article describes the clinical features, pathogenesis, prevalence, diagnosis, and management of myotonic dystrophy type 1 and myotonic dystrophy type 2.

RECENT FINDINGS

The prevalence of myotonic dystrophy type 1 is better understood than the prevalence of myotonic dystrophy type 2, and new evidence indicates that the risk of cancer is increased in patients with the myotonic dystrophies. In addition, descriptions of the clinical symptoms and relative risks of comorbidities such as cardiac arrhythmias associated with myotonic dystrophy type 1 have been improved.

Myotonic dystrophy type 1 and myotonic dystrophy type 2 are both characterized by progressive muscle weakness, early-onset cataracts, and myotonia. However, both disorders have multisystem manifestations that require a comprehensive management plan. While no disease-modifying therapies have yet been identified, advances in therapeutic development have a promising future.
Toxic Myopathies
Authors: Doughty Christopher T. , Amato Anthony A.
Published: December 2019

PURPOSE OF REVIEW

This article reviews the pathogenesis, clinical features, and management of toxic myopathy related to common medications, critical illness, and illicit substances.

RECENT FINDINGS

Muscle symptoms are common among statin users and are usually reversible after discontinuation of the statin; rarely, however, statins trigger an immune-mediated necrotizing myopathy that persists and requires immunomodulatory therapy. Autoantibodies targeting 3-hydroxy-3-methylglutaryl coenzyme A reductase can distinguish the toxic and immune-mediated forms. Immune checkpoint inhibitors, increasingly used in the treatment of advanced cancer, have recently been associated with the development of inflammatory myositis. A reversible mitochondrial myopathy has long been associated with zidovudine, but recent reports elucidate the risk of myopathy with newer antivirals, such as telbivudine and raltegravir.

The medications most commonly associated with myopathy include statins, amiodarone, chloroquine, hydroxychloroquine, colchicine, certain antivirals, and corticosteroids, and myopathy can occur with chronic alcoholism. Certain clinical, electrodiagnostic, and histologic features can aid in early recognition. Stopping the use of the offending agent reverses symptoms in most cases, but specific and timely treatment may be required in cases related to agents that trigger immune-mediated muscle injury.
Insights from mathematical modelling and quantitative analysis on the proposed 2030 goals for trachoma
Authors:   NTD Modelling Consortium discussion group on trachoma
Published: December 2019

Trachoma is a neglected tropical disease and the leading infectious cause of blindness worldwide. The current World Health Organization goal for trachoma is elimination as a public health problem, defined as reaching a prevalence of trachomatous inflammation-follicular below 5% in children (1-9 years) and a prevalence of trachomatous trichiasis in adults below 0.2%. Current targets to achieve elimination were set to 2020 but are being extended to 2030. Mathematical and statistical models suggest that 2030 is a realistic timeline for elimination as a public health problem in most trachoma endemic areas. Although the goal can be achieved, it is important to develop appropriate monitoring tools for surveillance after having achieved the elimination target to check for the possibility of resurgence. For this purpose, a standardized serological approach or the use of multiple diagnostics in complement would likely be required.
Factors that motivate individuals to volunteer to be dispatched as first responders in the event of a medical emergency: A systematic review protocol
Authors: Heffernan Eithne , Oving Iris , Barry Tomás , Phung Viet-Hai , Siriwardena Aloysius Niroshan , Masterson Siobhán
Published: December 2019

Background: Voluntary First Response is an important component of prehospital care for medical emergencies, particularly cardiac arrest, in many countries. This intervention entails the mobilisation of volunteers, known as Community First Responders (CFRs), by the Emergency Medical Services to respond to medical emergencies in their locality. They include lay responders and/or professional responders (e.g. police officers, fire fighters, and general practitioners). A wide variety of factors are thought to motivate CFRs to join and remain engaged in Voluntary First Response schemes, such as the availability of learning opportunities, recognition, counselling, and leadership. The aim of this review is to develop an in-depth understanding of CFR motivation, including the factors that influence the initial decision to volunteer as a CFR and the factors that sustain involvement in Voluntary First Response over time. Any factors relevant to CFR de-motivation and turnover will also be examined.

Methods: This is a protocol for a qualitative systematic review of the factors that influence the motivation of individuals to participate in Voluntary First Response. A systematic search will be carried out on seven electronic databases. Qualitative studies, mixed-methods studies, and any other studies producing data relating to the review question will be eligible for inclusion. Title and abstract screening, as well as full text screening, will be completed independently by two authors. A narrative synthesis, which is an established qualitative synthesis methodology, will be performed. The quality of each of the included studies will be critically appraised.

Discussion: The findings of this review will be used to optimise the intervention of Voluntary First Response. Specifically, the results will inform the design and organisation of Voluntary First Response schemes, including their recruitment, training, and psychological support processes. This could benefit a range of stakeholders, including CFRs, paramedics, emergency physicians, patients, and the public.
Attitudes towards transactional data donation and linkage in a longitudinal population study: evidence from the Avon Longitudinal Study of Parents and Children
Authors: Skatova Anya , Shiells Kate , Boyd Andy
Published: December 2019

Background: Commercial transaction records, such as data collected through banking and retail loyalty cards, present a novel opportunity for longitudinal population studies to capture data on participants’ real-world behaviours and interactions. However, little is known about participant attitudes towards donating transactional records for this purpose. This study aimed to: (i) explore the attitudes of longitudinal population study participants towards sharing their transactional records for health research and data linkage; and (ii) explore the safeguards that researchers should consider implementing when looking to request transactional data from participants for data linkage studies.

Methods: Participants in the Avon Longitudinal Study of Parents and Children were invited to a series of three focus groups with semi-structured discussions designed to elicit opinions. Through asking participants to attend three focus groups we aimed to facilitate more in-depth discussions around the potentially complex topic of data donation and linkage. Thematic analysis was used to sort data into overarching themes addressing the research questions.

Results: Participants (n= 20) expressed a variety of attitudes towards data linkage, which were associated with safeguards to address concerns. This data was sorted into three themes: information, trust, and control. We discuss the importance of explaining the purpose of data linkage, consent options, who the data is linked with and sensitivities associated with different parts of transactional data. We describe options for providing further information and controls that participants consider should be available when studies request access to transactional records.

Conclusions: This study provides initial evidence on the attitudes and concerns of participants of a longitudinal cohort study towards transactional record linkage. The findings suggest a number of safeguards which researchers should consider when looking to recruit participants for similar studies, such as the importance of ensuring participants have access to appropriate information, control over their data, and trust in the organisation.
Errors in the concepts and conduct of investigative actions
Authors: Лапин Евгений , Lapin Evgeniy
Published: December 2019

In the monograph on the basis of the analysis of special literature and generalization of materials of judicial and investigative practice typical mistakes made by scientists-lawyers, investigators and interrogators concerning definitions of concepts and production of investigative actions are shown. Attention is focused on tactical mistakes made not only in the production of investigative actions, but also in preparation for them. In addition, technical errors in the design of the Protocol drawn up upon the production of each investigative action are considered.
For teachers and students of law schools and faculties, as well as practitioners of criminal justice.
The molecular and genetic basis of carcinogenesis
Authors: Майборода Аскольд , Kaliagin Aleksei
Published: December 2019

The textbook deals with the classification of tumor growth, signs of malignancy, genetic basis of cancer, chronology of cellular events of oncogenesis. The differences between oncogenes and suppressor genes by the principle of action, the role of apoptosis in the processes of programmed cell death and their utilization are discussed. Attention is paid to the role of apoptosis defects in the development of oncogenic States. The modern ideas about the diagnosis of oncological diseases, which include screening examinations and individual verification of the tumor type, are generalized. The modern successes of diagnostic techniques, which were the result of the combined capabilities of molecular genetics and cytogenetics, are noted. The features of the course of virus-induced and non-viral forms of cancer are analyzed. Fundamental and clinical aspects of Oncology are combined.
Meets the requirements of the Federal state educational standards of higher education of the last generation.
For students on programs of specialization "Medical business", "Pediatrics", "Medical biochemistry". It will also be useful for residents and doctors.
Technological bases of extraction and processing of fuel and energy resources
Authors: Линник Юрий , Linnik Yuriy , Линник Владимир , Linnik Vladimir , Воронцов Виктор , Voroncov Viktor
Published: December 2019

The textbook covers the whole range of basic issues related to Geology, production and processing of natural gas, oil and coal.
Section I describes: the history of gas, oil and coal production; the current state and features of the development of the fuel and energy sector; challenges facing the oil and gas industry. Section II is devoted to the search and exploration of hydrocarbon deposits, hypotheses of their origin, features of occurrence and formation. Section III describes the technology of drilling, production, preparation and transportation of oil and gas, ways to increase oil and gas recovery collectors. Section IV deals with technology and mechanization of coal mining. Section V deals with oil, gas and coal refining.
Test questions for independent work of students and answers to them are presented in all sections of the textbook.
Meets the requirements of the Federal state educational standards of higher education of the last generation.
For students and teachers of universities, graduate students, as well as specialists of fuel and energy profile.
Hospitality and service in the food industry
Authors: Рождественская Лада , Rozhdestvenskaya Lada , Главчева Светлана , Glavcheva Svetlana , Чередниченко Лариса , Cherednichenko Larisa
Published: December 2019

The textbook discusses aspects of corporate culture and mission of the restaurant in the hospitality industry and service, as well as features of restaurant service and approaches to assessing its quality; describes the material and technical equipment of the processes of providing services, considers the organization of various types of service, highlights the ethical and aesthetic aspects of the activities of catering and standardization issues.
It is made taking into account modern normative legal documents, contains illustrations, tables and examples.
It is intended for bachelors studying in the areas of training 19.03.04 "production Technology and catering" and 38.03.02 "Management".
SNR-availability-based optical network provisioning
Authors: Kim Inwoong , Wang Xi , Vassilieva Olga , Palacharla Paparao , Ikeuchi Tadashi
Published: December 2019

We review recently proposed metrics, Q availability and signal-to-noise ratio (SNR) availability, based on statistical performance of optical signals, for modulation format assignment in network provisioning. These metrics assign a modulation format aiming to maximize spectral efficiency while satisfying the specified service availability. Q availability is suitable for tunable modulations with a discrete data rate based on M-ary quadrature amplitude modulations (mQAMs), while SNR availability is more suitable for fine-tunable modulations such as time-domain hybrid mQAM or a probabilistically shaped signal as well as discrete mQAMs. We also present a new guideline, to the best of our knowledge, on how to estimate network capacity without full network simulations when fine-tunable modulations are provisioned using SNR availability. We apply this guideline on three different network topologies and show 18.7% to 35.7% capacity gains with probabilistically shaped signal over mQAMs. SNR availability serves as a useful metric for provisioning in future optical networks adopting fine-tunable modulations.
Revisión y análisis de la sífilis venérea a través de la película El experimento Tuskegee / Miss Evers´ boys, en el marco de la asignatura de Microbiología y Cine
Authors: Rebellón Martínez Isabela , Salazar Balcázar Daniela , Castañeda Ramírez Claudia Rocío , Ocampo Toro Eliana
Published: December 2019

Alternativas innovadoras de enseñanza en el aula son fundamentales ante las limitaciones de la magistralidad. En este sentido, los desarrollos tecnológicos han permitido nuevas formas de enseñanza interactiva, en donde el Cine es un ejemplo significativo para la educación médica. A través del Cine es posible contextualizar conceptos básicos, clínicos e incluso humanistas de las enfermedades; por tanto, en este estudio se presenta una experiencia basada en cine para la enseñanza de enfermedades infecciosas y microbiología. Nosotros revisamos los aspectos históricos, epidemiológicos, microbiológicos y clínicos de la Sífilis a través de la película Miss Evers´ boys, seleccionando escenas claves para cada aspecto, y comparándolas con la literatura actual. Los resultados mostraron que la película refleja elementos importantes de la evolución, diagnóstico y tratamiento de la sífilis; en donde el entendimiento por parte de los estudiantes mejora, incluso ante la ausencia de escenas sobre el desarrollo completo de la enfermedad; por consiguiente, nosotros proponemos esta estrategia como una herramienta útil y significativa para el aprendizaje en esta y otras áreas.
Dos médicos detectives de Edimburgo unidos por la ficción
Authors: D’ottavio Callegari María Eugenia , D’ottavio Callegari María Silvia , D’ottavio Cattani Alberto Enrique
Published: December 2019

Una serie de cinco episodios (2000-2001) de la BBC narra ficcionalmente, mediante la resolución de varios casos policiales, la verdadera relación entre el Profesor Joseph Bell de la Escuela de Medicina (Universidad de Edimburgo, Escocia) y su discípulo Arthur Conan Doyle, quien se inspiró en la conducta investigativa metódica y la singular vestimenta de su maestro para construir su mítico personaje: Sherlock Holmes.
Tiempos de Guerra. El soldado que salvó Spielberg
Authors: Camaño Puig Ramón E. , Almudéver Campo Laura
Published: December 2019

Durante la Segunda Guerra Mundial, concretamente tras el Desembarco de Normandía, unos soldados norteamericanos capitaneados por Jonh Miller deben arriesgar sus vidas para salvar al soldado James Ryan, cuyos tres hermanos han muerto en la guerra. Lo único que se sabe del soldado Ryan es que se lanzó con su escuadrón de paracaidistas detrás de las líneas enemigas. El jefe del estado mayor ha ordenado devolverlo a su hogar, en Iowa, donde lo espera su desconsolada madre.Se trata de un filme bélico donde la muerte está siempre presente y en la cual, el soldado Ryan rememorará todas las vicisitudes por las que tuvieron que pasar los soldados para salvarlo.
Arrugas (2011) de Ignacio Ferreras. La enfermedad de Alzheimer a través del cómic y del cine
Authors: Abad Vila Miguel , Mayor Serrano María Blanca
Published: December 2019

La enfermedad de Alzheimer constituye la demencia más común entre las personas mayores. Sus devastadores efectos no se limitan exclusivamente a los enfermos, sino que afectan también a sus familiares y cuidadores. Debido a su elevado grado de dependencia, durante las etapas finales de la enfermedad muchos de estos pacientes pueden necesitar ser institucionalizados. Arrugas (2011) de Ignacio Ferreras, inspirada en el exitoso cómic homónimo (2007) del historietista Paco Roca, nos muestra las vicisitudes que su protagonista, Emilio, ha de atravesar cuando su familia decide ingresarlo en una residencia de ancianos y los vínculos que establece con otros internos, especialmente el desvergonzado y nihilista Miguel.
P015 Persistent Disparities in Colectomy Rate in Ulcerative Colitis
Authors: Bhurwal Abhishek , Seril Darren
Published: December 2019

BACKGROUND:

Colectomy is a curative treatment modality for ulcerative colitis (UC). Racial disparities have been described for colectomy in UC patients prior to the advent of anti-tumor necrosis factor (TNF) alpha agents. The goal of this study was to characterize racial and geographic trends in colectomy rates among hospitalized UC patients during the era of anti-TNF alpha agents.

METHODS:

A retrospective study was conducted utilizing the 2008–2014 National Inpatient Sample (NIS) database. Included were hospital discharges between the years 2010 and 2014, within the age range of 5–80 years, and with a primary diagnosis of UC identified by ICD-9-CM code of 556.x or primary diagnosis of complication of UC with a secondary or tertiary diagnosis of UC. Hospital administrative data were utilized to derive data for race and ethnicity and categorized into non-Hispanic white, African American, Hispanic, Asian or Pacific Islander, Native American, or other. ICD-9-CM procedure code 45.8 was applied to identify colectomy. Colectomy rates, in-hospital mortality, and length-of-stay were calculated for non-Hispanic whites, African Americans, and Hispanics. Data were analyzed with the Stata.

RESULTS:

The national estimate of the unadjusted colectomy rate among hospitalized UC patients between 2010 and 2014 was 3.90 per 1000 hospitalization days (95% confidence interval [CI] 3.72–4.08). The crude colectomy rates in African Americans (2.33) and Hispanics (3.99) were significantly lower than that of non-Hispanic whites (4.35, P < 0.001 and P < 0.009, respectively). After multivariate adjustment for confounders, the incidence rate ratio for African American versus whites was 0.43 (95% CI 0.32–0.58; P < 0.001). Medicare insurance was associated with a lower colectomy rate compared to possession of private insurance (3.83 vs 5.17; P < 0.0001). Assessment of colectomy rate by geographic region showed higher rates in the West (4.76) and Midwest (5.12) compared to the Northeast (3.20, P < 0.001 and P < 0.001, respectively).

CONCLUSION(S):

The nationwide rate of colectomy among hospitalized UC patients continues to vary significantly by race and geographic region in the era of anti-TNF alpha agents. Our analysis suggests that colectomy rates among hospitalized African Americans and Hispanics were lower than those of non-Hispanic whites during the 5-year period studied. There are multiple possible factors contributing to the observed racial differences in colectomy rates for UC, including differences in access to and utilization of healthcare resources, type of health insurance, and ethnic variation in healthcare literacy and attitudes toward the healthcare field. Further studies are needed to further elucidate the social and biologic underpinnings of these variations.
P025 Simplify in Capsule Endoscopy – TOP100 is a Swift and Reliable Evaluation Tool for the Inflammatory Activity in Crohn’s Disease
Authors: Freitas Marta , Arieira Cátia , Boal Carvalho Pedro , Bruno Rosa , Moreira Maria João , Cotter José
Published: December 2019

BACKGROUND:

Capsule endoscopy is a widely recognized method to study the small bowel, including in patients with suspected or established Crohn’s Disease (CD). The Lewis Score (LS) is a valuable tool in this setting, able to assess inflammatory activity. TOP 100, a new software tool of the RAPID Reader, emerged with the purpose of assisting in the time-consuming capsule reading process, by automatically selecting 100 images that will most likely contain abnormalities.

AIM:

Evaluate the agreement between TOP 100 and classic reading (CR) in determining LS in the setting of suspected or established CD.

METHODS:

Retrospective study including consecutive patients undergoing small bowel capsule endoscopy (SBCE) for suspected or established CD. One experienced reader performed CR, reported findings and calculated the LS. Another experienced reader, blinded to the CR results, reviewed all SBCE videos using TOP 100 and calculated the LS.

RESULTS:

One hundred fifteen patients were included, 86 females (74.8%), mean age of 36.2 ± 12.1 years. Eighty-one patients (70.4%) performed SBCE for suspected CD and 34 (29.6%) for established CD. SBCE detected significant inflammatory activity (LS ≥ 135) in 64 patients (55.2%). We verified a strong agreement between the two methods of capsule reading (Kappa = 0.83, P < 0.001), with an agreement on 89.6% of the cases. They agreed in 83.6% of SBCE with insignificant inflammatory activity (LS < 135) (Kappa = 0.83, P < 0.001), 76.4% in mild inflammatory activity (135 ≤ LS < 790) (Kappa = 0.78, P < 0.001) and 86.7% in moderate to severe disease (LS ≥ 790) (Kappa = 0.92, P < 0.001). All cases of moderate to severe inflammatory activity detected by CR were identified by TOP 100 as significant (LS ≥ 135) inflammatory activity. A good agreement was verified in all tertiles (P < 0.001).

CONCLUSION(S):

Although the classical review of the entire video remains the gold standard, the TOP 100 has been shown to be a useful tool in assisting the reader in a prompt calculation of LS, in particular for identifying patients with moderate to severe inflammatory disease.