bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chromosome End Repair and Genome Stability in
Plasmodium falciparum
Authors: Calhoun Susannah F. , Reed Jake , Alexander Noah , Mason Christopher E. , Deitsch Kirk W. , Kirkman Laura A. 
Published: August 2017

ABSTRACT

The human malaria parasite
Plasmodium falciparum
replicates within circulating red blood cells, where it is subjected to conditions that frequently cause DNA damage. The repair of DNA double-stranded breaks (DSBs) is thought to rely almost exclusively on homologous recombination (HR), due to a lack of efficient nonhomologous end joining. However, given that the parasite is haploid during this stage of its life cycle, the mechanisms involved in maintaining genome stability are poorly understood. Of particular interest are the subtelomeric regions of the chromosomes, which contain the majority of the multicopy variant antigen-encoding genes responsible for virulence and disease severity. Here, we show that parasites utilize a competitive balance between
de novo
telomere addition, also called “telomere healing,” and HR to stabilize chromosome ends. Products of both repair pathways were observed in response to DSBs that occurred spontaneously during routine
in vitro
culture or resulted from experimentally induced DSBs, demonstrating that both pathways are active in repairing DSBs within subtelomeric regions and that the pathway utilized was determined by the DNA sequences immediately surrounding the break. In combination, these two repair pathways enable parasites to efficiently maintain chromosome stability while also contributing to the generation of genetic diversity.

IMPORTANCE
Malaria is a major global health threat, causing approximately 430,000 deaths annually. This mosquito-transmitted disease is caused by
Plasmodium
parasites, with infection with the species
Plasmodium falciparum
being the most lethal. Mechanisms underlying DNA repair and maintenance of genome integrity in
P. falciparum
are not well understood and represent a gap in our understanding of how parasites survive the hostile environment of their vertebrate and insect hosts. Our work examines DNA repair in real time by using single-molecule real-time (SMRT) sequencing focused on the subtelomeric regions of the genome that harbor the multicopy gene families important for virulence and the maintenance of infection. We show that parasites utilize two competing molecular mechanisms to repair double-strand breaks, homologous recombination and
de novo
telomere addition, with the pathway used being determined by the surrounding DNA sequence. In combination, these two pathways balance the need to maintain genome stability with the selective advantage of generating antigenic diversity.
Answering medical questions at the point of care: a cross-sectional study comparing rapid decisions based on PubMed and Epistemonikos searches with evidence-based recommendations developed with the GRADE approach
Authors: Izcovich Ariel , Criniti Juan Martín , Popoff Federico , Ragusa Martín Alberto , Gigler Cristel , Gonzalez Malla Carlos , Clavijo Manuela , Manzotti Matias , Diaz Martín , Catalano Hugo Norberto , Neumann Ignacio , Guyatt Gordon 
Published: August 2017

IntroductionUsing the best current evidence to inform clinical decisions remains a challenge for clinicians. Given the scarcity of trustworthy clinical practice guidelines providing recommendations to answer clinicians’ daily questions, clinical decision support systems (ie, assistance in question identification and answering) emerge as an attractive alternative. The trustworthiness of the recommendations achieved by such systems is unknown.ObjectiveTo evaluate the trustworthiness of a question identification and answering system that delivers timely recommendations.DesignCross-sectional study.MethodsWe compared the responses to 100 clinical questions related to inpatient management provided by two rapid response methods with ‘Gold Standard’ recommendations. One of the rapid methods was based on PubMed and the other on Epistemonikos database. We defined our ‘Gold Standard’ as trustworthy published evidence-based recommendations or, when unavailable, recommendations developed locally by a panel of six clinicians following the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Recommendations provided by the rapid strategies were classified as potentially misleading or reasonable. We also determined if the potentially misleading recommendations could have been avoided with the appropriate implementation of searching and evidence summary tools.ResultsWe were able to answer all of the 100 questions with both rapid methods. Of the 200 recommendations obtained, 6.5% (95% CI 3% to 9.9%) were classified as potentially misleading and 93.5% (95% CI 90% to 96.9%) as reasonable. 6 of the 13 potentially misleading recommendations could have been avoided by the appropriate usage of the Epistemonikos matrix tool or by constructing summary of findings tables. No significant differences were observed between the evaluated rapid response methods.ConclusionA question answering service based on the GRADE approach proved feasible to implement and provided appropriate guidance for most identified questions. Our approach could help stakeholders in charge of managing resources and defining policies for patient care to improve evidence-based decision-making in an efficient and feasible manner.
Disease understanding in patients newly diagnosed with atrial fibrillation
Authors: Kaufman Brystana G , Kim Sunghee , Pieper Karen , Allen Larry A , Gersh Bernard J , Naccarelli Gerald V , Ezekowitz Michael D , Fonarow Gregg C , Mahaffey Kenneth W , Singer Daniel E , Chan Paul S , Freeman James V , Ansell Jack , Kowey Peter R , Rieffel James A , Piccini Jonathan , Peterson Eric , O’Brien Emily C 
Published: August 2017

ObjectiveTo describe self-reported disease understanding for newly diagnosed patients with atrial fibrillation (AF) and assess (1) how disease understanding changes over the first 6 months after diagnosis and (2) the relationship between patient understanding of therapies at baseline and treatment receipt at 6 months among treatment-naïve patients.MethodsWe analysed survey data from SATELLITE (Survey of Patient Knowledge and Personal Priorities for Treatment), a substudy of patients with new-onset AF enrolled in the national Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT) II registry across 56 US sites. Patients were surveyed at the baseline and 6-month follow-up clinic visits using Likert scales.ResultsAmong 1004 baseline survey responses, patients’ confidence in their understanding of rhythm control, ablation, anticoagulation and cardioversion was suboptimal, with ‘high’ understanding ranging from 8.5% for left atrial appendage closure to 71.3% for rhythm therapy. Of medical history and demographic factors, education level was the strongest predictor of reporting ‘high’ disease understanding. Among the 786 patients with 6-month survey data, significant increases in the proportion reporting high understanding were observed (p<0.05) only for warfarin and direct oral anticoagulants (DOACs). With the exception of ablation, high understanding for a given therapeutic option was not associated with increased use of that therapy at 6 months.ConclusionsAbout half of patients with new-onset AF understood the benefits of oral anticoagulant at the time of diagnosis and understanding improved over the first 6 months. However, understanding of AF treatment remains suboptimal at 6 months. Our results suggest a need for ongoing patient education.Clinical trial registrationClinicaltrials.gov. Identifier: NCT01701817.
Identifying mineral prospectivity using 3D magnetotelluric, potential field and geological data in the east Kimberley, Australia
Authors: Lindsay M. D. , Spratt J. , Occhipinti S. A. , Aitken A. R. A. , Dentith M. C. , Hollis J. A. , Tyler I. M. 
Published: August 2017

Abstract
An integrated interpretation of the east Kimberley, northern Western Australia was completed to determine mineral prospectivity, and was centred on a portion of a magnetotelluric (MT) survey conducted across the entire Kimberley Craton and surrounding orogens. A structural geophysical interpretation used potential field data, and was constrained by geological field observations, petrophysics, remote sensing and understanding of the tectonic history of the region. Potential field forward modelling located along the same survey traverse as the MT data allowed comparison between the two datasets and their interpretations revealing interesting features suggesting the presence of large-scale structures, the presence of mineralization deep in the crust, and where mineralization may be at or near the surface. The King River Fault is shown from both the MT inversion and potential field modelling as a crustal-scale, west-dipping structure, the footwall of which bounds the western side of a large resistive body. A conductive anomaly is also located on the hanging wall of the King River Fault. Our assessment suggests that graphitic rocks, most likely with some sulphide content, contribute to the strength of this anomaly, and highlights the potential of the east Kimberley to host graphite and base metal deposits.
Sequential hemifield gating of α- and β-behavioral performance oscillations after microsaccades
Authors: Bellet Joachim , Chen Chih-Yang , Hafed Ziad M. 
Published: August 2017

Microsaccades are tiny saccades that occur during gaze fixation. Even though visual processing has been shown to be strongly modulated close to the time of microsaccades, both at central and peripheral eccentricities, it is not clear how these eye movements might influence longer term fluctuations in brain activity and behavior. Here we found that visual processing is significantly affected and, in a rhythmic manner, even several hundreds of milliseconds after a microsaccade. Human visual detection efficiency, as measured by reaction time, exhibited coherent rhythmic oscillations in the α- and β-frequency bands for up to ~650–700 ms after a microsaccade. Surprisingly, the oscillations were sequentially pulsed across visual hemifields relative to microsaccade direction, first occurring in the same hemifield as the movement vector for ~400 ms and then the opposite. Such pulsing also affected perceptual detection performance. Our results suggest that visual processing is subject to long-lasting oscillations that are phase locked to microsaccade generation, and that these oscillations are dependent on microsaccade direction. NEW & NOTEWORTHY We investigated long-term microsaccadic influences on visual processing and found rhythmic oscillations in behavioral performance at α- and β-frequencies (~8–20 Hz). These oscillations were pulsed at a much lower frequency across visual hemifields, first occurring in the same hemifield as the microsaccade direction vector for ~400 ms before switching to the opposite hemifield for a similar interval. Our results suggest that saccades temporally organize visual processing and that such organization can sequentially switch hemifields.
Differential Toxicity in Patients with and without DNA Repair Mutations: Phase I Study of Carboplatin and Talazoparib in Advanced Solid Tumors
Authors: Dhawan Mallika S. , Bartelink Imke H. , Aggarwal Rahul Raj , Leng Jim , Zhang Jenna Z. , Pawlowska Nela , Terranova-Barberio Manuela , Grabowsky Jennifer A. , Gewitz Andrew , Chien Amy J. , Moasser Mark , Kelley Robin K. , Maktabi Tayeba , Thomas Scott , Munster Pamela N. 
Published: August 2017

Abstract
Purpose: The PARP inhibitor (PARPi) talazoparib may potentiate activity of chemotherapy and toxicity in cells vulnerable to DNA damage.
Experimental Design: This phase I study evaluated the safety, tolerability, pharmacokinetics, and efficacy of talazoparib and carboplatin. Pharmacokinetic modeling explored associations between DNA vulnerability and hematologic toxicity.
Results: Twenty-four patients (eight males; 16 females) with solid tumors were enrolled in four cohorts at 0.75 and 1 mg daily talazoparib and weekly carboplatin (AUC 1 and 1.5, every 2 weeks or every 3 weeks), including 14 patients (58%) with prior platinum treatment. Dose-limiting toxicities included grade 3 fatigue and grade 4 thrombocytopenia; the MTD was not reached. Grade 3/4 toxicities included fatigue (13%), neutropenia (63%), thrombocytopenia (29%), and anemia (38%). After cycle 2's dose, delays/reductions were required in all patients. One complete and two partial responses occurred in germline BRCA1/2 (gBRCA1/2) patients. Four patients showed stable disease beyond 4 months, three of which had known mutations in DNA repair pathways. Pharmacokinetic toxicity modeling suggests that after three cycles of carboplatin AUC 1.5 every 3 weeks and talazoparib 1 mg daily, neutrophil counts decreased 78% [confidence interval (CI), 87–68] from baseline in gBRCA carriers and 63% (CI, 72–55) in noncarriers (P &lt; 0.001). Pharmacokinetic toxicity modeling suggests an intermittent, pulse dosing schedule of PARP inhibition, differentiated by gBRCA mutation status, may improve the benefit/risk ratio of combination therapy.
Conclusions: Carboplatin and talazoparib showed efficacy in DNA damage mutation carriers, but hematologic toxicity was more pronounced in gBRCA carriers. Carboplatin is best combined with intermittent talazoparib dosing differentiated by germline and somatic DNA damage mutation carriers. Clin Cancer Res; 23(21); 6400–10. ©2017 AACR.
The Rimthan Arch, basin architecture, and stratigraphic trap potential in Saudi Arabia
Authors: Wharton Stanley Rich 
Published: August 2017

The Rimthan Arch, situated between the Arabian carbonate platform and the Gotnia intrashelf basin, represents a world class hydrocarbon province in Saudi Arabia. Middle to Upper Jurassic shallow-water depositional sequences are associated with productive hydrocarbon fields in which challenges exist in defining exploration targets, mainly stratigraphic trap plays. An attempt is made to investigate the basin depositional architecture on the flank of the Arch and also to model the stratigraphic trap potential of the youngest Arab third-order sequence. The basin architecture, stratal geometries, and impact of tectonics are explored using 3D seismic and well data. Seismic chronostratigraphy, seismic stratigraphy, seismic attribute, and log-based reservoir heterogeneity techniques are applied as an integrated approach to interpret the sequences from basin to reservoir scale. The study identifies two second-order sequences, SEQ 1 and SEQ 2, to frame a 3D geologic model and to examine basin development through time. Results derived from the integrated study indicate that although initial basin subsidence began later in SEQ 1 north of the Arch, it increased appreciably during SEQ 2. The Dhruma J20 maximum flooding surface, Lower Fadhili, and Hanifa provide clues in tracking major basin changes. Seismic stratigraphy applications highlight reflection terminations and prograding stratal geometries throughout the stratigraphic section to demonstrate tectonoeustatic influences. Tectonics impact SEQ 2 more intensely than SEQ 1 and may influence the migration of hydrocarbons across juxtaposed lithologies. A complex association between shallow marine tidal and ramp carbonates, and deeper basin halite beds, is linked to the subsiding Gotnia Basin. Log-facies analysis of the Arab third-order sequence demonstrates reservoir and seal trends, including the stratigraphic entrapment potential along a carbonate ramp profile. Seismic attributes support reservoir-depositional trends and salt-bed geometries. The integrated approach provides a targeted workflow to investigate the complex depositional systems and their stratigraphic trapping potential on the Arch.
Oral medicine and the elderly
Authors: McCreary Christine , Ríordáin Richeal Ní 
Published: August 2017

A focus often exists in dental practice on the maintenance and management of the dentition and the periodontium, however, conditions of the oral mucosa and orofacial pain can cause significant problems for older patients. Oral mucosal conditions are more prevalent in older patients and many orofacial pain disorders, such as burning mouth syndrome and trigeminal neuralgia, are more common in patients over the age of 50 years. Although these conditions may not be routinely managed in general practice, identification of these patients in primary care and appropriate referral will lead to more prompt and effective treatment. Clinical Relevance: Dental practitioners need to be able to identify what is considered to be within the normal physiological limits of the ageing oral tissue and hence what is abnormal and requires further investigation to facilitate appropriate referral.
Genealogy of Source Material for Its Use in Apple Breeding in Southern Russia
Authors: Dubravina Irina , Vasilenko Igor , Chepinoga Irina , Gorlov Sergey 
Published: August 2017

Abstract
Prebreeding research on Malus domestica Borkh. specimens was conducted to broaden the genetic diversity of cross breeding components for faster creation of cultivars of adaptive and technological orientation. Genealogical analysis has practical value in the study of the apple trees gene pool for accelerated development of cultivars with desired properties. Genealogical analysis of 55 apple cultivars from the gene pool of branch of the Department of Horticulture of Kuban State Agrarian University - Krymsk Experimental breeding station (Krymsk), complex donors were selected by traits of immunity to scab and high quality of fruits - ‘Gold Rush’, ‘Pristine’, ‘Enterprise’. Cultivar ‘Golden Delicious’ was selected as a “hidden” donor by the trait of medium (autumn) ripening time.
A Questionnaire for Assessing Fear of Radiotherapy in Oncology Patients
Authors: Radojevic Marija Zivkovic , Folic Marko , Jankovic Slobodan 
Published: August 2017

Abstract
Radiotherapy is a frequently prescribed and highly effective form of treatment of oncology patients. However, many patients feel rational or irrational fear of the application of radiotherapy, which may provoke mental and physical stress, anxiety, growing anger and hostility, thus reducing quality of life. The aim of this study was to develop, reliability test and validate a questionnaire for assessing the level of fear of radiotherapy in oncology patients.
We performed a prospective qualitative study based on the development, validation and reliability testing of the questionnaire developed for assessing radiotherapy-caused fear in oncology patients treated in the Centre for Oncology and Radiology, Department of Radiotherapy, Clinical Centre Kragujevac.
The study included 154 patients and the final version of the questionnaire integrated 15 questions. After the elimination of inappropriate questions the Cronbach coefficient α was 0.946. The questionnaire consists of two factors which represent 57.423% and 6.925%, making a total of 64.348% of the variance of the questionnaire.
The results of our study show that the questionnaire used is a unique, reliable and valid instrument for assessing the level of fear of radiotherapy in oncology patients the application of which will allow us to identify patients with elevated levels of fear of radiotherapy.
Learning and Stress Shape the Reward Response Patterns of Serotonin Neurons
Authors: Zhong Weixin , Li Yi , Feng Qiru , Luo Minmin 
Published: August 2017

The ability to predict reward promotes animal survival. Both dopamine neurons in the ventral tegmental area and serotonin neurons in the dorsal raphe nucleus (DRN) participate in reward processing. Although the learning effects on dopamine neurons have been extensively characterized, it remains largely unknown how the response of serotonin neurons evolves during learning. Moreover, although stress is known to strongly influence reward-related behavior, we know very little about how stress modulates neuronal reward responses. By monitoring Ca2+signals during the entire process of Pavlovian conditioning, we here show that learning differentially shapes the response patterns of serotonin neurons and dopamine neurons in mice of either sex. Serotonin neurons gradually develop a slow ramp-up response to the reward-predicting cue, and ultimately remain responsive to the reward, whereas dopamine neurons increase their response to the cue but reduce their response to the reward. For both neuron types, the responses to the cue and the reward depend on reward value, are reversible when the reward is omitted, and are rapidly reinstated by restoring the reward. We also found that stressors including head restraint and fearful context substantially reduce the response strength of both neuron types, to both the cue and the reward. These results reveal the dynamic nature of the reward responses, support the hypothesis that DRN serotonin neurons signal the current likelihood of receiving a net benefit, and suggest that the inhibitory effect of stress on the reward responses of serotonin neurons and dopamine neurons may contribute to stress-induced anhedonia.SIGNIFICANCE STATEMENTBoth serotonin neurons in the dorsal raphe and dopamine neurons in the ventral tegmental area are intimately involved in reward processing. Using long-term fiber photometry of Ca2+signals from freely behaving mice, we here show that learning produces a ramp-up activation pattern in serotonin neurons that differs from that in dopamine neurons, indicating complementary roles for these two neuron types in reward processing. Moreover, stress treatment substantially reduces the reward responses of both serotonin neurons and dopamine neurons, suggesting a possible physiological basis for stress-induced anhedonia.
International cooperation for student mobility: the case of Umesp and Zuyd
Authors: Martins Vanessa , Montague Alexandra , Silva Paulo Bessa Da 
Published: August 2017

This paper briefly contextualizes the internationalization of universities, its main concepts, historical aspects, motivations and realities emphasizing the Brazilian and Dutch contexts. It describes the institutional cooperation between the Methodist University of Sao Paulo (UMESP) – Brazil and the Zuyd University of Applied Sciences (ZUYD), in the Netherlands. Focus is placed on the exchange of students for the semester mobility program. It makes a narrative since the beginning of the partnership, describing its objectives, the way it evolved and the outcome during the period. Special attention is given to the successes and challenges to operate the program. Student evaluations were analyzed to determine future improvements for the exchange.
ВВЕДЕНИЕ В ЭКСЕРГЕТИЧЕСКИЙ АНАЛИЗ АБСОРБЦИОННО-РЕЗОРБЦИОННОЙ ХОЛОДИЛЬНОЙ МАШИНЫ
Authors: Морозюк Л. И. , Грудка Б. Г. 
Published: August 2017

Эксергетический метод термодинамического анализа стал неотъемлемым элементом научных исследований в области холодильной и теплонасосной техники. Информация, полученная в результате эксергетического анализа более масштабная по сравнению с другими видами анализа, например, энергетического. Это в первую очередь относится к абсорбционным машинам, наиболее сложному и менее изученному типу холодильных машин. В работе представлен алгоритм углубленного эксергетического анализа абсорбционно-резорбционной холодильной машины как частного случая абсорбционной, в которой сумма физической и химической эксергии используется для каждого потока вещества.
МАТЕМАТИЧЕСКОЕ МОДЕЛИРОВАНИЕ РАБОЧИХ РЕЖИМОВ ДЕФЛЕГМАТОРА АБСОРБ-ЦИОННОГО ВОДОАММИАЧНОГО ХОЛОДИЛЬНОГО АГРЕГАТА В СИСТЕМАХ ПОЛУЧЕНИЯ ВОДЫ ИЗ АТМОСФЕРНОГО ВОЗДУХА С ИСПОЛЬЗОВАНИЕМ СОЛНЕЧНОЙ ЭНЕРГИИ
Authors: Осадчук Е. А. , Кирилов В. Х. 
Published: August 2017

Разработана математическая модель режимов пленочного течения с восходящим потоком паровой смеси с высокоэффективным отводом тепла в режиме вынужденной конвекции. Проведена оценка параметров пленочного течения жидкости и парового потока (скорости и числа Рейнольдса) для типичных значений диаметров труб дефлегматора 20, 32 и 40 мм. Показано, что режим пленочного течения ламинарный, а парового потока – развитый турбулентный, причем толщина пленки практически неизменна для рассматриваемых размеров труб дефлегматора.