bluuebunny/crossref_metadata_2025_split huggingface dataset:
Undisclosed financial ties between guideline writers and pharmaceutical companies: a cross-sectional study across 10 disease categories
Authors: Moynihan Ray , Lai Alexandra , Jarvis Huw , Duggan Geraint , Goodrick Stephanie , Beller Elaine , Bero Lisa 
Published: February 2019

ObjectivesTo investigate the proportion of potentially relevant undisclosed financial ties between clinical practice guideline writers and pharmaceutical companies.DesignCross-sectional study of a stratified random sample of Australian guidelines and writers.SettingGuidelines available from Australia’s National Health and Medical Research Council guideline database, 2012–2014, stratified across 10 health priority areas.Population402 authors of 33 guidelines, including up to four from each area, dependent on availability: arthritis/musculoskeletal (3); asthma (4); cancer (4); cardiovascular (4); diabetes (4); injury (3); kidney/urogenital (4); mental health (4); neurological (1); obesity (1). For guideline writers with no disclosures, or who disclosed no ties, a search of disclosures in the medical literature in the 5 years prior to guideline publication identified potentially relevant ties, undisclosed in guidelines. Guidelines were included if they contained recommendations of medicines, and writers included if developing or writing guidelines.Main outcome measuresProportions of guideline writers with potentially relevant undisclosed financial ties to pharmaceutical companies active in the therapeutic area; proportion of guidelines including at least one writer with a potentially relevant undisclosed tie.Results344 of 402 writers (86%; 95% CI 82% to 89%) either had no published disclosures (228) or disclosed they had no ties (116). Of the 344 with no disclosed ties, 83 (24%; 95% CI 20% to 29%) had potentially relevant undisclosed ties. Of 33 guidelines, 23 (70%; 95% CI 51% to 84%) included at least one writer with a potentially relevant undisclosed tie. Writers of guidelines developed and funded by governments were less likely to have undisclosed financial ties (8.1%vs30.6%; risk ratio 0.26; 95% CI 0.13 to 0.53; p<0.001).ConclusionsAlmost one in four guideline writers with no disclosed ties may have potentially relevant undisclosed ties to pharmaceutical companies. These data confirm the need for strategies to ensure greater transparency and more independence in relationships between guidelines and industry.
The (
h,k
)-Server Problem on Bounded Depth Trees
Authors: Bansal Nikhil , Eliéš Marek , Jeż Łukasz , Koumoutsos Grigorios 
Published: February 2019

We study the
k
-server problem in the resource augmentation setting, i.e., when the performance of the online algorithm with
k
servers is compared to the offline optimal solution with
h
≤
k
servers. The problem is very poorly understood beyond uniform metrics. For this special case, the classic
k
-server algorithms are roughly (1+1/ϵ)-competitive when
k
=(1+ϵ)
h
, for any ϵ > 0. Surprisingly, however, no
o
(
h
)-competitive algorithm is known even for HSTs of depth 2 and even when
k
/
h
is arbitrarily large.

We obtain several new results for the problem. First, we show that the known
k
-server algorithms do not work even on very simple metrics. In particular, the Double Coverage algorithm has competitive ratio Ω (
h
) irrespective of the value of
k
, even for depth-2 HSTs. Similarly, the Work Function Algorithm, which is believed to be optimal for all metric spaces when
k
=
h
, has competitive ratio Ω (
h
) on depth-3 HSTs even if
k
=2
h
. Our main result is a new algorithm that is
O
(1)-competitive for constant depth trees, whenever
k
=(1+ϵ)
h
for any ϵ > 0. Finally, we give a general lower bound that any deterministic online algorithm has competitive ratio at least 2.4 even for depth-2 HSTs and when
k
/
h
is arbitrarily large. This gives a surprising qualitative separation between uniform metrics and depth-2 HSTs for the (
h
,
k
)-server problem.
Sensorimotor uncertainty modulates corticospinal excitability during skilled object manipulation
Authors: Davare Marco , Parikh Pranav J. , Santello Marco 
Published: February 2019

Sensorimotor memory built through previous hand-object interactions allows subjects to plan grasp forces. The memory-based mechanism is particularly effective when contact points on the object do not change across multiple manipulations, thus allowing subjects to generate the same forces in a feedforward fashion. However, allowing subjects to choose where to grasp an object causes trial-to-trial variability in fingertip positioning, suggesting a decreased ability to predict where the object will be grasped. In this scenario, subjects modulate forces on a trial-to-trial basis as a function of fingertip positioning. We suggested that this fingertip force-to-position modulation could be implemented by transforming feedback of digit placement into an accurate distribution of fingertip forces. Thus, decreasing certainty of fingertip position on an object would cause a shift from predominantly memory- to feedback-based force control mechanisms. To gain further insight into these sensorimotor transformation mechanisms, we asked subjects to grasp and lift an object with an asymmetrical center of mass while preventing it from tilting. To isolate the effect of digit placement uncertainty, we designed two experimental conditions that differed in terms of predictability of fingertip position but had similar average fingertip positioning and force distribution. We measured corticospinal excitability to probe possible changes in sensorimotor processing associated with digit placement uncertainty. We found a differential effect of sensorimotor uncertainty after but not before object contact. Our results suggest that sensorimotor integration is rapidly tuned after object contact based on different processing demands for memory versus feedback mechanisms underlying the control of manipulative forces. NEW & NOTEWORTHY The relative contribution of predictive and feedback mechanisms for scaling digit forces to position during dexterous manipulation depends on the predictability of where the object will be grasped. We found that corticospinal excitability shortly after contact was sensitive to digit position predictability. This supports the proposition that distinct sensorimotor integration processes are engaged, depending on the role of feedback about digit placement versus sensorimotor memory in controlling manipulative forces.
GM-CSF Promotes Antitumor Immunity by Inducing Th9 Cell Responses
Authors: Kim Il-Kyu , Koh Choong-Hyun , Jeon Insu , Shin Kwang-Soo , Kang Tae-Seung , Bae Eun-Ah , Seo Hyungseok , Ko Hyun-Ja , Kim Byung-Seok , Chung Yeonseok , Kang Chang-Yuil 
Published: February 2019

Abstract
GM-CSF as an adjuvant has been shown to promote antitumor immunity in mice and humans; however, the underlying mechanism of GM-CSF–induced antitumor immunity remains incompletely understood. In this study, we demonstrate that GM-CSF potentiates the efficacy of cancer vaccines through IL9-producing Th (Th9) cells. GM-CSF selectively enhanced Th9 cell differentiation by regulating the COX2–PGE2 pathway while inhibiting the differentiation of induced regulatory T (iTreg) cells in vitro and in vivo. GM-CSF–activated monocyte-derived dendritic cells converted tumor-specific naïve Th cells into Th9 cells, and delayed tumor growth by inducing antitumor CTLs in an IL9-dependent manner. Our findings reveal a mechanism for the adjuvanticity of GM-CSF and provide a rationale for the use of GM-CSF in cancer vaccines.
Renal Consequences of Therapeutic Interventions in Premature Neonates
Authors: Fryer Hayley J. , Welsh Gavin I. 
Published: February 2019

An infant is described as “preterm” if they are born before 37 weeks of gestation. As nephrogenesis does not complete until 36 weeks of gestation, premature infants are often born with underdeveloped kidneys. Current evidence strongly suggests that this leaves those born prematurely more susceptible to developing kidney-related conditions later in life. Although the incidence of premature birth steadily increases each year in the United Kingdom, reports of perinatal death following preterm labour are falling. This is mainly attributed to the development of antenatal drugs, such as tocolytics, corticosteroids and antibiotics. Though these drugs have effectively reduced the incidence of premature-birth-related deaths, evidence suggests that they may be nephrotoxic. This review will describe the experimental evidence that some therapeutics are disadvantageous to kidney functions later on in life.
АЛГОРИТМ ДІАГНОСТИКИ МІГРУЮЧОЇ ЕРИТЕМИ В ДІТЕЙ
Authors: Nykytyuk S. O. 
Published: February 2019

Мета роботи – встановити передумови і частоту природного зараження B. burgdorferi sensu lato від кліщів, відібраних після укусу дітей у Тернопільській області в різні місяці року, а також визначити методи контролю за укусами кліщів у дітей.
Матеріали і методи. Було обстежено 291 дитину, яка зазнала нападу кліщів. Батьки усіх обстежених відповіли на запитання уніфікованої міжнародної анкети. В лабораторії медичного університету протягом липня-жовтня 2017 р. було досліджено 169 кліщів, взятих із шкіри дітей. Використовували метод полімеразної ланцюгової реакції (ПЛР) в режимі реального часу, проводили двоступеневу серологічну експертизу: скринінговий тест ELISA на наявність антитіл IgM/IgG, Western blot.
Результати. Хвороба Лайма проявляється у багатьох клінічних формах. Чим молодша дитина, тим складніше діагностувати хворобу Лайма.
Висновки. Відзначено високу частоту реєстрації випадків захворювання на Лайм-бореліоз серед міських жителів. У 38,3 % досліджених від моменту укусу кліща до його видалення минуло більше 24 год. Випадки захворювання на Лайм-бореліоз реєструвалися протягом усього року, з піками в липні й жовтні. 29,0 % кліщів виявилися інфікованими. Наявності в анамнезі контакту з кліщем, ураженим B. burgdorferi, та виникнення у пацієнта мігруючої еритеми (МЕ) достатньо для того, щоб діагностувати хворобу Лайма та розпочати лікування. За допомогою двоступеневої серологічної діагностики вдалося виявити антитіла до Borrelia burgdorferi sensu lato у 52,0 % обстежених дітей.
ЖОВТА ГАРЯЧКА: ЕПІДЕМІОЛОГІЯ, КЛІНІКА, ДІАГНОСТИКА ТА ПРОФІЛАКТИКА
Authors: Andreychyn M. A. , Nychyk N. A. , Zavidniuk N. H. , Iosyk Ia. I. 
Published: February 2019

Мета роботи – узагальнити дані про етіологію, епідеміологічні особливості, клінічні прояви та лабораторну діагностику жовтої гарячки (ЖГ), подати основні рекомендації ВООЗ і CDC стосовно її профілактики та лікування.
Наведено найновіші дані про ЖГ, особливості її розповсюдження. Вірус ЖГ (ВЖГ) належить до родини флавівірусів. Основним резервуаром збудника у природних осередках є мавпи, додатковим – можливо їжаки, сумчасті, гризуни, у яких інфекція перебігає латентно. ВЖГ потрапляє до людини при укусі інфікованого комара. Хвороба реєструється в Африці, Центральній та Південній Америці. Природний осере­док ЖГ на обох континентах підтримується завдяки циркуляції вірусу серед лісових комарів і диких приматів. Передача збудника людині відбувається в лісовому (джунглевому, сільському), проміжному та міському осередках. Найнебезпечніший в епідеміологічному плані є останній, який реалізується серед неімунних людей, внаслідок переміщення заражених осіб або шляхом випадкового перевезення інфікованих комарів. Тяжкий клінічний перебіг та ускладнення свідчать про особливу небезпеку цієї хвороби для людства. Інкубаційний період зазвичай становить 3-6 діб, рідко може досягати 10 діб. У типових випадках спостерігається три періоди хвороби: початковий гарячковий, період ремісії зі зниженням температури тіла і період венозного стазу. Летальність складає 5-10 %, в період епідемії – до 60 % і вище. Для ЖГ можливі також легкі, стерті, абортивні форми без жовтяниці й геморагічного синдрому. Для верифікації діагнозу впродовж 5 днів з моменту появи симптомів використовують полімеразну ланцюгову реакцію зі зворотною транскрипцією та серологічну діагностику (ELISA). Ефективного етіотропного методу лікування ще не розроблено, використовуються лише патогенетичні засоби. Натепер єдиним методом боротьби з цією інфекцією, згідно з рекомендаціями ВООЗ і CDC, є вакцинація. Щеплення необхідно зробити принаймні за 10 днів до подорожі в ендемічну місцевість. Обов’язково вакцинують працівників профільних лабораторій з групи ризику зараження. З 11 липня 2016 року ВООЗ прийняла рішення про виключення повторної вакцинації, оскільки одноразова доза забезпечує пожиттєвий імунітет.
Prevalence of Microvascular and Endothelial Dysfunction in the Nonculprit Territory in Patients With Acute Myocardial Infarction
Authors: Díez-Delhoyo Felipe , Gutiérrez-Ibañes Enrique , Sanz-Ruiz Ricardo , Vázquez-Álvarez María Eugenia , González Saldívar Hugo , Rivera Juárez Allan , Sarnago Fernando , Martínez-Sellés Manuel , Bermejo Javier , Soriano Javier , Elízaga Jaime , Fernández-Avilés Francisco 
Published: February 2019

Background:
Approximately half of the patients presenting with ST-segment–elevation myocardial infarction (STEMI) have multivessel disease. The physiology of the nonculprit artery has not been thoroughly studied to date. We sought to characterize the coronary physiology of the nonculprit artery in the early phase after STEMI and determine the real prevalence of microvascular and endothelial dysfunction.

Methods and Results:
Patients with STEMI and another coronary artery lesion in a different territory were prospectively included in an observational single-center study. The protocol took place after revascularization of the culprit artery and comprised 3 phases: first, epicardial endothelial functional assessment using intracoronary acetylcholine; second, epicardial severity quantification based on fractional flow reserve, and nonendothelial microvascular function with coronary flow reserve and the index of microvascular resistance; third, endothelium-dependent microvascular function assessment based on the endothelial coronary flow reserve. Eighty-four patients were included. Mean age was 62±10 years, and 86.9% were men. Only 6 subjects had a nonpathological study: macrovascular endothelial dysfunction was present in 60% of the patients; fractional flow reserve ≤0.8, coronary flow reserve <2, and index of microvascular resistance >25 were evident in 34%, 37%, and 28% of the subjects respectively; and microvascular endothelial dysfunction (endothelial coronary flow reserve <1.5) was observed in 44%. In hospital-mortality was 0%, and no major complications occurred. At 6-month follow-up, there were no events related to the nonculprit artery.

Conclusions:
Microvascular and endothelial dysfunction in the nonculprit artery territory in patients with STEMI are very common. In 93% of the patients, we found functional abnormalities. Acetylcholine administration in the early phase post-STEMI in patients with multivessel disease is safe.
High-Impact Extratropical Cyclones along the Northeast Coast of the United States in a Long Coupled Climate Model Simulation
Authors: Catalano Arielle J. , Broccoli Anthony J. , Kapnick Sarah B. , Janoski Tyler P. 
Published: February 2019

Abstract
High-impact extratropical cyclones (ETCs) cause considerable damage along the northeast coast of the United States through strong winds and inundation, but these relatively rare events are difficult to analyze owing to limited historical records. Using a 1505-yr simulation from the GFDL FLOR coupled model, statistical analyses of extreme events are performed including exceedance probability computations to compare estimates from shorter segments to estimates that could be obtained from a record of considerable length. The most extreme events possess characteristics including exceptionally low central pressure, hurricane-force winds, and a large surge potential, which would greatly impact nearby regions. Return level estimates of metrics of ETC intensity using shorter, historical-length segments of the FLOR simulation are underestimated compared to levels determined using the full simulation. This indicates that if the underlying distributions of observed ETC metrics are similar to those of the 1505-yr FLOR distributions, the actual frequency of extreme ETC events could also be underestimated. Comparisons between FLOR and reanalysis products suggest that not all features of simulated high-impact ETCs are representative of observations. Spatial track densities are similar, but FLOR exhibits a negative bias in central pressure and a positive bias in wind speed, particularly for more intense events. Although the existence of these model biases precludes the quantitative use of model-derived return statistics as a substitute for those derived from shorter observational records, this work suggests that statistics from future models of higher fidelity could be used to better constrain the probability of extreme ETC events and their impacts.
Cognitive-motor interference in walking after stroke: test–retest reliability and validity of dual-task walking assessments
Authors: Tsang Charlotte Sau Lan , Chong Doris Yin Kei , Pang Marco Yiu Chung 
Published: February 2019

Objective: To explore the reliability and validity of a series of dual-task mobility assessments among individuals post-stroke. Design: Observational study with repeated measures. Setting: University laboratory. Participants: Thirty community-dwelling individuals with chronic stroke. Interventions: Not applicable. Main Measures: Each of the two mobility tasks (1-minute level-ground walking with and without obstacle-negotiation) was performed concurrently with each of the eight cognitive tasks (auditory Stroop test, serial subtraction, shopping list recall and category naming at two difficulty levels). Walking distance and obstacle hitting rate (OHR) indicated dual-task mobility performance. Number of correct responses (NCR) indicated cognitive performance. Reaction time was additionally measured for the auditory Stroop test. Construct validity was examined by correlations between the dual-task assessments. The dual-task assessments were repeated within 7–14 days for test–retest reliability. Results: Excellent test–retest reliability in walking distance and OHR was found (intraclass correlation coefficient, ICC(3,1) = 0.891–0.984, P < 0.05). Moderate to excellent reliability was found in NCR and reaction time (ICC(3,1) = 0.480–0.911, P < 0.01). Correlations between walking distance were excellent ( rs = 0.840–0.985, P < 0.01). Correlations of NCR and reaction time between low- and high-level cognitive tasks were mostly moderate to excellent ( rs  = 0.515–0.793, P < 0.01). Generally no significant correlations were found in NCR between the dual-task assessments with different cognitive domains. Conclusion: The dual-task walking assessments are reliable and valid for evaluating cognitive-motor interference in community-dwelling individuals post-stroke. The lack of correlations between the tasks of different cognitive domains indicates the need of using different cognitive domains in dual-task walking assessment post-stroke.
Fertility parameters and reproductive management of Norwegian Forest Cats, Maine Coon, Persian and Bengal cats raised in Italy: a questionnaire-based study
Authors: Romagnoli Stefano , Bensaia Chiara , Ferré-Dolcet Lluis , Sontas Hasan Besim , Stelletta Calogero 
Published: February 2019

Objectives Fertility and reproductive management were investigated, via questionnaires, in breeding establishments of Norwegian Forest Cats, Maine Coon, Persian and Bengal cats in Italy. Methods Six Bengal, five Maine Coon, eight Norwegian Forest Cat and seven Persian breeders responded for a total of 128 queens, 565 heats, 337 litters and 1424 kittens spanning the period 1998–2012. The mean number of queens per cattery was 4.9 ± 2.3, with primiparous queens constituting 20.5%. Of the catteries, 61.5% were indoor, with 50% of them having access to a fenced balcony. Fifteen percent of the catteries were outdoor with cat runs. No light supplementation was used in any of the catteries. Results Queens showed oestrous cycles throughout the year, although 67% of oestrous cycles occurred from January–June. Puberty occurred, on average, at 12.3 ± 7.4 months. Pregnancy diagnosis was performed routinely in only 30% of catteries. Both pregnancy length (average 64.7 ± 2.4 days, range 59–76 days) and litter size (average 4.2 ± 1.8 kittens, with 11.8% of kittens stillborn) showed some breed-specific differences; in Norwegian Forest Cats larger litter size was associated with shorter pregnancy length. Kitten mortality between birth and weaning was, on average, 14%. Stillborn kittens ( P <0.01) and kitten mortality (0.01 < P <0.05) increased with litter size. In Maine Coons and Persians, a total of 3% of parturitions occurred via caesarean section (CS); litters born via CS were larger and characterised by a greater number of stillborn kittens and kitten mortality. Conclusions and relevance No previous data concerning reproductive patterns of pedigree cats raised in Southern Europe are available. Feline reproductive management should be adjusted for latitude owing to different climate and daylight patterns that may have an impact on feline reproduction.
The effect of physiological stretch and the valvular endothelium on mitral valve proteomes
Authors: Ali Mir S , Wang Xinmei , Lacerda Carla MR 
Published: February 2019

Heart valves reside in a dynamic mechanical environment experiencing a multitude of forces. These forces have been shown to play a key role in valvular pathophysiology. However, knowledge of proteins involved in valvular mechanobiology is limited to only a few proteins of interest, namely, α-smooth muscle actin, transforming growth factor β, etc. Valvular endothelium mediates valvular homeostasis and controls valvular interstitial cell phenotype transformation. But, how endothelium mediates valvular response to dynamic forces is also unknown. In this study, proteomic analysis of mitral valve anterior leaflets under 10% cyclic radial strain was performed. Endothelium from these samples was removed to test how endothelium mediates mitral valve response to stretch. Results show that stretch downregulated cytoskeletal proteins and proteins involved in energy metabolism such as glycolysis and oxireductase activity. Endothelium removal resulted in downregulation of extracellular matrix and cell-matrix adhesion proteins. Removal of endothelium also resulted in upregulation of translation-related and chaperone proteins. Overall, this high throughput study provides insights into new protein groups that may be involved in mitral valve response to mechanical stretch and loss of endothelium.Impact statementThis work is important to the field of heart valve pathophysiology as it provides new insights into molecular markers of mechanically induced valvular degeneration as well as the protective role of the valvular endothelium. These discoveries reported here advance our current knowledge of the valvular endothelium and how its removal essentially takes valve leaflets into an environmental shock. In addition, it shows that static conditions represent a mild pathological state for valve leaflets, while 10% cyclic stretch provides valvular cell quiescence. These findings impact the field by informing disease stages and by providing potential new drug targets to reverse or slow down valvular change before it affects cardiac function.