bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractBackgroundThe 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.MethodsBloodfed 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.ResultsAnopheles 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.ConclusionsMultiple 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

AbstractSynucleinopathies [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

AbstractAn 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

Abstract
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

AbstractThe 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

AbstractThe 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

AbstractLung 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

AbstractMuscles 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

Summary
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

ABSTRACT

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.

SUMMARY
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

ABSTRACT

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.

SUMMARY
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.
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.
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.