bluuebunny/crossref_metadata_2025 huggingface dataset:
Phosphorylation of FtsZ and FtsA by a DNA Damage-Responsive Ser/Thr Protein Kinase Affects Their Functional Interactions in
Deinococcus radiodurans
Authors: Maurya Ganesh K. , Modi Kruti , Banerjee Manisha , Chaudhary Reema , Rajpurohit Yogendra S. , Misra Hari S.
Published: July 2018

The LexA/RecA-type SOS response is the only characterized mechanism of DNA damage response in bacteria. It regulates cell cycle by attenuating the functions of cell division protein FtsZ and inducing the expression of DNA repair proteins. There are bacteria, including
Deinococcus radiodurans
, that do not show this classical SOS response.
D. radiodurans
is known for its extraordinary resistance to gamma radiation, and a DNA damage-responsive Ser/Thr protein kinase (RqkA) has been characterized for its role in radioresistance. RqkA phosphorylates a large number of proteins in solution. The phosphorylation of RecA and PprA by RqkA enhanced their activities. FtsZ phosphorylation is inducible by gamma radiation in wild-type
D. radiodurans
but not in an
rqkA
mutant. Phosphorylation affected the interaction of FtsZ and FtsA in this bacterium. This study, therefore, brought forth some findings that might lead to the discovery of a new mechanism regulating the bacterial cell cycle in response to DNA damage.
Factors associated with additional anterior cruciate ligament reconstruction and register comparison: a systematic review on the Scandinavian knee ligament registers
Authors: Svantesson Eleonor , Hamrin Senorski Eric , Baldari Angelo , Ayeni Olufemi R. , Engebretsen Lars , Franceschi Francesco , Karlsson Jon , Samuelsson Kristian
Published: July 2018

Objective

To present an overview of the Scandinavian knee ligament registers with regard to factors associated with additional ACL reconstruction, and studies comparing the Scandinavian registers with other knee ligament registers.

Design

Systematic review.

Data sources

Four electronic databases: PubMed, EMBASE, the Cochrane Library and AMED were searched, and 157 studies were identified. Two reviewers independently screened titles, abstracts and full-text studies for eligibility. A modified version of the Downs and Black checklist was applied for quality appraisal.

Eligibility criteria for selecting studies

Eligible studies were those published since the establishment of the Scandinavian registers in 2004, which reported factors associated with additional ACL reconstruction and compared data from other registers.

Results

Thirty-one studies met the inclusion criteria and generally displayed good reporting quality. Adolescent age (<20 years) was the most common factor associated with additional ACL reconstruction. The choice of hamstring tendon graft compared with patella tendon, transportal femoral tunnel drilling, smaller graft diameter and utilisation of suspensory fixation devices were associated with additional ACL reconstruction. Concomitant cartilage injury decreased the likelihood of additional ACL reconstruction. Patient sex alone did not influence the likelihood. The demographics of patients undergoing ACL reconstruction in the Scandinavian registers are comparable to registers in other geographical settings. However, there are differences in surgical factors including the presence of intra-articular pathology and graft choice.

The studies published from the Scandinavian registers in general have a high reporting quality when regarded as cohort studies. Several factors are associated with undergoing additional ACL reconstruction. The results from the registers may help facilitate treatment decisions.
Pharmacological and non-pharmacological treatments for major depressive disorder: review of systematic reviews
Authors: Gartlehner Gerald , Wagner Gernot , Matyas Nina , Titscher Viktoria , Greimel Judith , Lux Linda , Gaynes Bradley N , Viswanathan Meera , Patel Sheila , Lohr Kathleen N
Published: July 2018

Objectives

This study aims to summarise the evidence on more than 140 pharmacological and non-pharmacological treatment options for major depressive disorder (MDD) and to evaluate the confidence that patients and clinicians can have in the underlying science about their effects.

Design

This is a review of systematic reviews.

Data sources

This study used MEDLINE, Embase, Cochrane Library, PsycINFO and Epistemonikos from 2011 up to February 2017 for systematic reviews of randomised controlled trials in adult patients with acute-phase MDD.

Methods

We dually reviewed abstracts and full-text articles, rated the risk of bias of eligible systematic reviews and graded the strength of evidence.

Results

Nineteen systematic reviews provided data on 28 comparisons of interest. For general efficacy, only second-generation antidepressants were supported with high strength evidence, presenting small beneficial treatment effects (standardised mean difference: −0.35; 95% CI −0.31 to −0.38), and a statistically significantly higher rate of discontinuation because of adverse events than patients on placebo (relative risk (RR) 1.88; 95% CI 1.0 to 3.28).

Only cognitive behavioural therapy is supported by reliable evidence (moderate strength of evidence) to produce responses to treatment similar to those of second-generation antidepressants (45.5% vs 44.2%; RR 1.10; 95% CI 0.93 to 1.30). All remaining comparisons of non-pharmacological treatments with second-generation antidepressants either led to inconclusive results or had substantial methodological shortcomings (low or insufficient strength of evidence).

Conclusions

In contrast to pharmacological treatments, the majority of non-pharmacological interventions for treating patients with MDD are not evidence based. For patients with strong preferences against pharmacological treatments, clinicians should focus on therapies that have been compared directly with antidepressants.

Trial registration number

International Prospective Register of Systematic Reviews (PROSPERO) registration number: 42016035580.
Deprescribing in primary care in Portugal (DePil17-20): a three-phase observational and experimental study protocol
Authors: Simões Pedro Augusto , Santiago Luiz Miguel , Simões José Augusto
Published: July 2018

Introduction

Polypharmacy is commonly defined as the simultaneous taking of five or more drugs. Deprescribing is the process of tapering or stopping medications with the aim of improving patient outcomes and optimising current therapy, and there are several tools aiming at identifying potentially inappropriate medications, especially in the elderly. The direct involvement of patients and their caregivers in the choice and administration of drugs has long been known to be very important, but it is not usually applied. The aim of this study is to assess the knowledge of older adults about deprescription, the effect on willingness to have regular medications deprescribed and its quality-of-life outcome.

Methods and analysis

This study protocol comprises three phases. The first two phases will be nationwide and aim to evaluate the prevalence and patterns of polypharmacy and assess the barriers and facilitators of deprescribing perceived by older adults, as well as their willingness to have regular medications deprescribed and to self-medicate. The third and last phase will be a non-pharmacological randomised clinical study to measure older patients’ acceptance to have regular medications deprescribed and related quality of life.

Ethics and dissemination

The study will be conducted in accordance with the principles expressed in the Declaration of Helsinki. It has been approved by the Ethics Committee of the University of Beira Interior and Portuguese National Data Protection Commission. Study results will be published in peer-reviewed journals and presented at national and international conferences. In short, no action will be taken without written consent from patients and doctors.

Trial registration number

>NCT03283735.
Sex differences in the 1-year risk of dying following all-cause and cause-specific hospital admission after age 50 in comparison with a general and non-hospitalised population: a register-based cohort study of the Danish population
Authors: Höhn Andreas , Larsen Lisbeth Aagaard , Schneider Daniel Christoph , Lindahl-Jacobsen Rune , Rau Roland , Christensen Kaare , Oksuzyan Anna
Published: July 2018

Objectives

We examine the mortality of men and women within the first year after all-cause and cause-specific hospital admission to investigate whether the sex differences in mortality after hospitalisation are higher than in the corresponding general and non-hospitalised population.

Design

This is a population-based, longitudinal study with nationwide coverage. The study population was identified by linking the National Patient Register with the Central Population Register using a 5% random sample of the Danish population.

Setting

The population born between 1898 and 1961, who was alive and residing in Denmark after 1977, was followed up between 1977 and 2011 with respect to hospital admissions and mortality while aged 50–79.

Primary outcome measures

The absolute sex differences in the 1-year risk of dying after all-cause and cause-specific hospital admission. The hospitalised population sex differentials were then compared with the sex differences in a general and a non-hospitalised population, randomly matched by age, sex and hospitalisation status.

Results

The risk of dying was consistently higher for hospitalised men and women. At all ages, the absolute sex differences in mortality were largest in the hospitalised population, were smaller in the general population and were smallest in the non-hospitalised population. This pattern was consistent across all-cause admissions, and with respect to admissions for neoplasms, circulatory diseases and respiratory diseases. For all-cause hospital admissions, absolute sex differences in the 1-year risk of dying resulted in 43.8 excess male deaths per 1,000 individuals within the age range 50–79, while the levels were lower in the general and the non-hospitalised population, at levels of 13.5 and 6.6, respectively.

Conclusions

This study indicates a larger male disadvantage in mortality following hospitalisation, pointing towards an association between the health status of a population and the magnitude of the female advantage in mortality.
To intubate or not: ventilation is the question. A manikin-based observational study
Authors: Sall Fatimata Seydou , De Luca Alban , Pazart Lionel , Pugin Aurore , Capellier Gilles , Khoury Abdo
Published: July 2018

Introduction

There is a continuous debate concerning the superiority of endotracheal intubation on bag-valve-mask (BVM) ventilation in patients with cardiac arrest. In this manikin-based observational study, we evaluate and compare the performance of manual ventilation through a facemask (BVM) and an endotracheal tube (ETT).

Methods

One hundred and forty healthcare providers were instructed to manually ventilate a manikin as they would do for a 75 kg adult patient in respiratory arrest. Each one was ventilating both through a facemask and an ETT for a 5 min period in a random order. Ventilatory parameters were measured by the ASL 5000 lung simulator and ventilation performance was analysed using a sliding window method published in a previous study to assess accurately ventilation efficiency.

Results

The mean ventilation rate was high whatever the technique used (24 bpm). A weak relationship between manual ventilation performance and the type of interface used was observed (p=0.0484). The overall rate of adequate ventilation was low even if we noticed a slight improvement when ventilating through an ETT (13.21% vs 7.5% of adequate ventilation). However, the rate of hyperventilation did not differ between mask and tube (79% vs 77%). A significant relationship is observed between professional category, the size of the hand squeezing the bag and manual ventilation performance (p<0.05).

Conclusion

Whatever the interface used, healthcare professionals are still struggling to perform manual ventilation efficiently according to international guidelines. Ventilation with an ETT does not prove to be significantly more efficient than with a facemask. It would be therefore important to recentre the debate on controlling ventilatory parameters with current devices. Focusing on training may maximise manual ventilation efficiency and minimise the loss of time during cardiopulmonary resuscitation.
Narrative review of injuries in powerlifting with special reference to their association to the squat, bench press and deadlift
Authors: Bengtsson Victor , Berglund Lars , Aasa Ulrika
Published: July 2018

Pain and injuries are considered a common problem among elite athletes and recreational lifters performing the squat, bench press and deadlift. Since all three lifts engage multiple joints and expose the lifters’ bodies to high physical demands often several times a week, it has been suggested that their injuries might be related to the excessively heavy loads, the large range of motion during the exercises, insufficient resting times between training sessions and/or faulty lifting technique. However, no previous article has summarised what is known about specific injuries and the injury aetiology associated with the three lifts. Thus, the aim of this narrative review was to summarise what is known about the relationships between the powerlifting exercises and the specific injuries or movement impairments that are common among lifters and recreationally active individuals.
Self-reported chronic injuries in climbing: who gets injured when?
Authors: Grønhaug Gudmund
Published: July 2018

Objectives

To assess self-reported chronic injuries in climbing and possible connections with gender, experience and style of climbing.

Method

Retrospective survey.

Setting

Web-based questionnaire.

Participants

667 active climbers (385 with chronic injuries, 289 males and 96 females).

Main outcome measure

Climbers who had experienced at least one chronic injury during the last 6 months.

Result

About 2/3 of male outdoor climbers had experienced a chronic injury. The three most frequent sites of injury were fingers (41.3%), shoulders (19.4%) and elbows (17.7%). The most frequent injury for the females were fingers (29.2%), shoulder (21.9%), wrist (12.5%), elbow (11.5%) and foot/ankle (10.4%). The most frequent injuries for the male were fingers (45.3%), elbow (19.7%) and shoulder (18.7%). Respondents who preferred outdoor climbing were more prone to injury than others.

Conclusion

Fingers were the most prevalent site of injury regardless of level of experience, gender and whether level of expertise is reported in terms of bouldering or route climbing. There seems to be a gender difference in respect of site of injury prevalence and a different prevalence of injuries according to style of climbing and different levels of expertise. Furthermore, the use of the suggested way of reporting levels of expertise to compare between bouldering and route climbing seems to be robust with no huge differences in terms of incidence level of different injuries.
The predictive value of fall assessment tools for patients admitted to hospice care
Authors: Patrick Rebecca J , Slobodian Dana , Debanne Sara , Huang Ying , Wellman Charles
Published: July 2018

Objectives

Fall assessment tools are commonly used to evaluate the likelihood of fall. For patients found to be at high risk, patient-specific fall prevention interventions are implemented. The purposes of this study were to describe the population, evaluate and compare the efficacy of fall assessment tools, and suggest the best use for these tools in hospice.

Methods

Data were downloaded from the electronic medical record for all patients who were admitted to and died in hospice care in 2013. Variables included demographic, clinical and initial fall assessment scores that had been computed on admission to hospice care, using our standard fall assessment tool. To facilitate comparison among three tools, additional fall assessment calculations were made for each patient using the Morse Fall Scale and MACH-10, two tools commonly used in a variety of healthcare settings.

Results

Data were available for 3446 hospice patients. Female patients were less likely to fall than males; Fallers lived longer than Nonfallers; and patients with a primary dementia diagnosis fell 10 days sooner than those with a primary non-dementia diagnosis. A comparison of three fall assessment tools revealed that no tool had a good positive predictive value, but each demonstrated a good negative predictive value.

Conclusions

Fall assessment scores should not be used as the sole predictor of likelihood of fall, and are best used as a supplement to clinical judgement. Patients with a primary dementia diagnosis are likely to fall earlier in their hospice care than those with other primary diagnoses.
Predictors of medium-term mortality in patients hospitalised with coronary artery disease in a resource-limited South-East Asian setting
Authors: Qanitha Andriany , Uiterwaal Cuno S. P. M. , Henriques Jose P. S. , Mappangara Idar , Idris Irfan , Amir Muzakkir , de Mol Bastianus A. J. M.
Published: July 2018

Objective

To measure medium-term outcomes and determine the predictors of mortality in patients with coronary artery disease (CAD) both during and after hospitalisation in a resource-limited South-East Asian setting.

Methods

From February 2013 to December 2014, we conducted a prospective observational cohort study of 477 patients admitted to Makassar Cardiac Center, Indonesia, with acute coronary syndrome and stable CAD. We actively obtained data on clinical outcomes and after-discharge management until April 2017. Multivariable Cox proportional hazard analysis was performed to examine predictors for our primary outcome, all-cause mortality.

Results

From hospital admission, patients were followed over a median of 18 (IQR 6–36) months; in total 154 (32.3%) patients died. More patients with acute myocardial infarction died in the hospital compared with patients with unstable and stable angina (p=0.002). Over the total follow-up, there was a difference in mortality between non-ST-segment elevation myocardial infarction (n=41, 48.2%), ST-segment elevation myocardial infarction (n=65, 30.8%), unstable angina (n=18, 26.5%) and stable coronary artery disease (n=30, 26.5%) groups (p=0.007). The independent predictors of all-cause mortality were hyperglycaemia on admission (HR 1.55 (95% CI 1.12 to 2.14), p=0.008), heart failure/Killip class ≥2 (HR 2.50 (95% CI 1.76 to 3.56), p<0.001), estimated glomerular filtration rate <60 mL/min (HR 1.77 (95% CI 1.26 to 2.50), p=0.001), no revascularisation (percutaneous coronary intervention/coronary artery bypass grafting) (HR 2.38 (95% CI 1.31 to 4.33), p=0.005) and poor adherence to after-discharge medications (HR 10.28 (95% CI 5.52 to 19.16), p<0.001). Poor medication adherence predicted postdischarge mortality and did so irrespective of underlying CAD diagnosis (p interaction=0.88).

Conclusions

Patients with CAD in a poor South-East Asian setting experience high in-hospital and medium-term mortality. The initial severity of the disease, lack of access to guidelines-recommended therapy and poor adherence to after-discharge medications are the main drivers for excess mortality. Improved access to early and late hospital care and patient education should be prioritised for better survival.
ModelHeart: a resident-led implementation of metrics to reduce 30-day heart failure readmissions
Authors: Kachur Sergey , Kachur Patricia , Akhtar Tauseef , Collado Elias , Espinosa-Friedman Martha , Asher Craig , Hernandez Marlow , Tabaquin Stephen
Published: July 2018

Hospitals have been penalised for excessive 30-day readmissions via Medicare payment penalties. As such there has been keen interest in finding ways of reducing readmissions. The basis for the study was a retrospective review of heart failure (HF) admissions at Cleveland Clinic Florida from 1 January 2010 to 31 December 2010. The result of this was a set of metrics associated with >30 day span between admissions: N-terminal pro-brain natriuretic peptide by at least 23%, fluid balance of ≤−1.3 L and sodium ≥135 mEq/L on discharge. The ModelHeart trial was a prospective resident-led validation of these criteria that consisted of education about and implementation of these metrics. A total of 200 patients carrying a diagnosis of HF, admitted between 1 November 2012 and 14 January 2014 were included in the trial. Of the 200 enrolled patients, 94% of discharged patients met at least one criteria, 58% met at least two criteria and 20% met all three. There were forty-eight all-cause 30-day readmissions. 30-day readmission rates between themore than equal to two criteria cohort and the remaining patients were not significantly different (p=0.71). Overall readmission rates were higher in the 2011–2012 retrospective patient pool (19%) versus the ModelHeart cohort (11%), and proportional differences were significant, (p<0.001). This may suggest that education provided sufficient awareness to alter discharge practices outside of the measured metrics. However, the lack of significant differences between groups with respect to discharge metrics suggests that further study is needed to refine the metrics and that reducing HF readmissions involves a continuum of care that spans the inpatient and outpatient setting.
Productivity burden of smoking in Australia: a life table modelling study
Authors: Owen Alice J , Maulida Salsabil B , Zomer Ella , Liew Danny
Published: July 2018

Objectives

This study aimed to examine the impact of smoking on productivity in Australia, in terms of years of life lost, quality-adjusted life years (QALYs) lost and the novel measure of productivity-adjusted life years (PALYs) lost.

Methods

Life table modelling using contemporary Australian data simulated follow-up of current smokers aged 20–69 years until age 70 years. Excess mortality, health-related quality of life decrements and relative reduction in productivity attributable to smoking were sourced from published data. The gross domestic product (GDP) per equivalent full-time (EFT) worker in Australia in 2016 was used to estimate the cost of productivity loss attributable to smoking at a population level.

Results

At present, approximately 2.5 million Australians (17.4%) aged between 20 and 69 years are smokers. Assuming follow-up of this population until the age of 70 years, more than 3.1 million years of life would be lost to smoking, as well as 6.0 million QALYs and 2.5 million PALYs. This equates to 4.2% of years of life, 9.4% QALYs and 6.0% PALYs lost among Australian working-age smokers. At an individual level, this is equivalent to 1.2 years of life, 2.4 QALYs and 1.0 PALY lost per smoker. Assuming (conservatively) that each PALY in Australia is equivalent to $A157 000 (GDP per EFT worker in 2016), the economic impact of lost productivity would amount to $A388 billion.

Conclusions

This study highlights the potential health and productivity gains that may be achieved from further tobacco control measures in Australia via application of PALYs, which are a novel, and readily estimable, measure of the impact of health and health risk factors on work productivity.
Geometric momentum and angular momentum for charge-monopole system
Authors: Xiao S. F. , Liu Q. H.
Published: July 2018

For a charge-monopole pair, we have another definition of the orbital angular momentum, and the transverse part of the momentum including the vector potential turns out to be the so-called geometric momentum that is under intensive study recently. For the charge on the spherical surface with the monopole at the origin, the commutation relations between all components of both the geometric momentum and the orbital angular momentum satisfy the so(3,[Formula: see text]1) algebra. With construction of the geometrically infinitesimal displacement operator based on the geometric momentum, the so(3,[Formula: see text]1) algebra implies the Aharonov–Bohm phase shift. The related problems such as charge and flux quantization are also addressed.
Testing Lorentz symmetry violation with an invariant minimum speed
Authors: Nassif Cláudio , Amaro de Faria A. C. , dos Santos Rodrigo Francisco
Published: July 2018

This work presents an experimental test of Lorentz invariance violation in the infrared (IR) regime by means of an invariant minimum speed in spacetime and its effects on the time when an atomic clock given by a certain radioactive single-atom (e.g. isotope Na[Formula: see text]) is a thermometer for an ultracold gas like the dipolar gas Na[Formula: see text]K[Formula: see text]. So, according to a Deformed Special Relativity (DSR) so-called Symmetrical Special Relativity (SSR), where there emerges an invariant minimum speed V in the subatomic world, one expects that the proper time of such a clock moving close to V in thermal equilibrium with the ultracold gas is dilated with respect to the improper time given in lab, i.e. the proper time at ultracold systems elapses faster than the improper one for an observer in the lab, thus leading to the so-called proper time dilation so that the atomic decay rate of an ultracold radioactive sample (e.g. Na[Formula: see text]) becomes larger than the decay rate of the same sample at room temperature. This means a suppression of the half-life time of a radioactive sample thermalized with an ultracold cloud of dipolar gas to be investigated by NASA in the Cold Atom Lab (CAL).
Global Dynamics of a Cooperative Discrete System in the Plane
Authors: Bilgin Arzu , Brett Ann , Kulenović Mustafa R. S. , Pilav Esmir
Published: July 2018

In this paper, we consider the cooperative system [Formula: see text] where all parameters [Formula: see text] are positive numbers and the initial conditions [Formula: see text] are nonnegative numbers. We describe the global dynamics of this system in a number of cases. An interesting feature of this system is that it exhibits a coexistence of locally stable equilibrium and locally stable periodic solutions as well as the Allee effect.
Lyapunov Exponents, Sensitivity, and Stability for Non-Autonomous Discrete Systems
Authors: Shao Hua , Shi Yuming , Zhu Hao
Published: July 2018

This paper focuses on the relationships of Lyapunov exponents with sensitivity and stability for non-autonomous discrete systems. Some new concepts are introduced for non-autonomous discrete systems, including Lyapunov exponents, strong sensitivity at a point and in a set, Lyapunov stability, and exponential asymptotical stability. It is shown that the positive Lyapunov exponent at a point implies strong sensitivity for a class of non-autonomous discrete systems. Furthermore, the uniformly positive Lyapunov exponents in a totally invariant set imply strong sensitivity in this set under certain conditions. The negative Lyapunov exponent at a point implies exponential asymptotical stability for a class of non-autonomous discrete systems. The related existing results for autonomous discrete systems are generalized to non-autonomous discrete systems and their conditions are weakened. One example is provided for illustration.
Experimental Investigation of a Walk-in Refrigerator Performance using R290 as a Retrofit for R22
Authors: El-Sayed A. R. , El Morsi M. , Mahmoud N. A.
Published: July 2018

An experimental performance study is performed on a refrigeration system equipped with a scroll compressor and tested with R22 using an electronic expansion valve (EEV) as an expansion device and controlled by proportional-integral-derivative (PID) control method. The system is tested at [Formula: see text]C, [Formula: see text]C, [Formula: see text]C, 0[Formula: see text]C and 4[Formula: see text]C evaporator air temperature and 20[Formula: see text]C, 25[Formula: see text]C and 30[Formula: see text]C condenser inlet water temperature at 50[Formula: see text]Hz compressor driving frequency and 50[Formula: see text]Hz evaporator fans driving frequency. R22 reached the set point at all temperatures except [Formula: see text]C evaporator temperature with 30[Formula: see text]C condenser temperature due to the severe increase in the compressor discharge temperature that could result in the lubricating oil burnout. Then, the system is retrofitted with a reciprocating compressor especially designed to be used with R290 and tested with R290 at the same evaporator and condenser temperatures using EEV as an expansion device. R290 reached all set points at all evaporator and condenser temperatures. Also, R290 was able to reach all evaporator temperatures at higher condenser temperatures, 35[Formula: see text]C and 40[Formula: see text]C, and this will be discussed in future work. The results show that using R290, the pulldown time decreases by 30.3–71.4%, the ON time ratio decreases by 1–23.6%, the compressor discharge temperature decreases by 46.6–81[Formula: see text]C, the refrigerant mass flow rate decreases by 28.8–50.4%, VRC decreases by 15.2–32.5%, the compressor power consumption decreases by 34.4–44.3% and coefficient of performance (COP) increases by 35–115.5%.
How Does Domain Expertise Affect Users’ Search Interaction and Outcome in Exploratory Search?
Authors: Mao Jiaxin , Liu Yiqun , Kando Noriko , Zhang Min , Ma Shaoping
Published: July 2018

People often conduct exploratory search to explore unfamiliar information space and learn new knowledge. While supporting the highly dynamic and interactive exploratory search is still challenging for the search system, we want to investigate which factors can make the exploratory search successful and satisfying from the user’s perspective. Previous research suggests that domain experts have different search strategies and are more successful in finding domain-specific information, but how the domain expertise level will influence users’ interaction and search outcomes in exploratory search, especially in different knowledge domains, is still unclear. In this work, via a carefully designed user study that involves 30 participants, we investigate the influence of domain expertise levels on the interaction and outcome of exploratory search in three different domains: environment, medicine, and politics. We record participants’ search behaviors, including their explicit feedback and eye fixation sequences, in a laboratory setting. With this dataset, we identify both domain-independent and domain-dependent effects on user behaviors and search outcomes. Our results extend existing research on the effect of domain expertise in search and suggest different strategies for exploiting domain expertise to support exploratory search in different knowledge domains.
An Epidemiological Review of Diet and Cutaneous Malignant Melanoma
Authors: Yang Keming , Fung Teresa T. , Nan Hongmei
Published: July 2018

Incidence of cutaneous malignant melanoma has continued to rise despite public efforts to promote sun protection behaviors among populations at risk. However, dietary factors may also affect the development of melanoma. In the past few decades, findings from epidemiologic and experimental research have linked consumption of several foods and other nutrients to the risk of melanoma. Caffeine has been associated with a lower risk of melanoma, and citrus fruits and alcohol with increased risk. Associations between polyunsaturated fatty acid, niacin/nicotinamide, folate, and vitamin D with melanoma remain controversial. Diet likely influences melanoma development through several potential mechanisms, such as enhancing UV-induced apoptosis and increasing photosensitivity. We conducted a narrative review to summarize recent epidemiologic studies of diet and melanoma based on published literature. Given the high prevalence of the food items and nutrients covered in this review and the decades-long rising melanoma incidence worldwide, the associations we discuss may have important public health implications in terms of reducing melanoma incidence through dietary modification. Cancer Epidemiol Biomarkers Prev; 27(10); 1115–22. ©2018 AACR.
Wnt3a/β-Catenin Signaling Conditions Differentiation of Partially Exhausted T-effector Cells in Human Cancers
Authors: Schinzari Valeria , Timperi Eleonora , Pecora Giulia , Palmucci Francesco , Gallerano Daniela , Grimaldi Alessio , Covino Daniela Angela , Guglielmo Nicola , Melandro Fabio , Manzi Emy , Sagnotta Andrea , Lancellotti Francesco , Sacco Luca , Chirletti Piero , Grazi Gian Luca , Rossi Massimo , Barnaba Vincenzo
Published: July 2018

In this study, we investigated the role of the Wnt/β-catenin signaling pathway in antitumor immune responses. We report that the concentration of secreted Wnt3a was significantly higher in conditioned medium from tumor or nontumor tissues obtained from all hepatocellular carcinoma or colorectal cancer patients tested, than in serum of healthy donors or patients. In addition, both Wnt3a and β-catenin were overexpressed by tumor-infiltrating and nontumor-infiltrating CD4+ or CD8+ T cells. The majority of these T cells expressed a dysfunctional effector memory Eomes+T-bet−phenotype that we defined as partially exhausted, because they performed effector functions (in terms of interferon-γ and tumor necrosis factor-α production, as well as CD107a mobilization) despite their PD-1 expression. Wnt3a/β-catenin signaling in T naïve cells in vitro recapitulated the T-cell setting in vivo. Indeed, the differentiation of cultured T naïve cells was arrested, producing cells that resembled the EomeshighT-betlowβ-cateninhigh T cells with moderate effector functions that infiltrated tumor and nontumor areas. Wnt3a blockade improved the capacity of T naïve cells to differentiate into effector cells in vitro. However, Wnt3a blockade did not affect the function and phenotype of differentiated, partially exhausted, tumor-infiltrating T cells ex vivo. Taken together, our data suggest that Wnt3a blockade halts the capacity of Wnt/β-catenin signaling to inhibit the differentiation of T naïve cells, but it does not restore the dysfunction of differentiated T cells, in the tumor setting. Cancer Immunol Res; 6(8); 941–52. ©2018 AACR.
Wnt3a Neutralization Enhances T-cell Responses through Indirect Mechanisms and Restrains Tumor Growth
Authors: Pacella Ilenia , Cammarata Ilenia , Focaccetti Chiara , Miacci Stefano , Gulino Alessandro , Tripodo Claudio , Ravà Micol , Barnaba Vincenzo , Piconese Silvia
Published: July 2018

The Wnt/β-catenin pathway regulates T-cell functions, including the repression of effector functions to the advantage of memory development via Tcf1. In a companion study, we demonstrate that, in human cancers, Wnt3a/β-catenin signaling maintains tumor-infiltrating T cells in a partially exhausted status. Here, we have investigated the effects of Wnt3a neutralization in vivo in a mouse tumor model. Abundant Wnt3a was released, mostly by stromal cells, in the tumor microenvironment. We tested whether Wnt3a neutralization in vivo could rescue the effector capacity of tumor-infiltrating T cells, by administering an antibody to Wnt3a to tumor-bearing mice. This therapy restrained tumor growth and favored the expansion of tumor antigen–specific CD8+ effector memory T cells with increased expression of Tbet and IFNγ and reduced expression of Tcf1. However, the effect was not attributable to the interruption of T-cell–intrinsic β-catenin signaling, because Wnt3a/β-catenin activation correlated with enhanced, not reduced, T-cell effector functions both ex vivo and in vitro. Adoptively transferred CD8+ T cells, not directly exposed to the anti-Wnt3a antibody but infiltrating previously Wnt3a-neutralized tumors, also showed improved functions. The rescue of T-cell response was thus secondary to T-cell–extrinsic changes that likely involved dendritic cells. Indeed, tumor-derived Wnt3a strongly suppressed dendritic cell maturation in vitro, and anti-Wnt3a treatment rescued dendritic cell activities in vivo. Our results clarify the function of the Wnt3a/β-catenin pathway in antitumor effector T cells and suggest that Wnt3a neutralization might be a promising immunotherapy for rescuing dendritic cell activities. Cancer Immunol Res; 6(8); 953–64. ©2018 AACR.
Mechanisms by Which Dendritic Cells Present Tumor Microparticle Antigens to CD8+ T Cells
Authors: Ma Jingwei , Wei Keke , Zhang Huafeng , Tang Ke , Li Fei , Zhang Tianzhen , Liu Junwei , Xu Pingwei , Yu Yuandong , Sun Weiwei , Zhu LiYan , Chen Jie , Zhou Li , Liang Xiaoyu , Lv Jiadi , Fiskesund Roland , Liu Yuying , Huang Bo
Published: July 2018

Tumor cell–derived microparticles (T-MP) contain tumor antigen profiles as well as innate signals, endowing them with vaccine potential; however, the precise mechanism by which DCs present T-MP antigens to T cells remains unclear. Here, we show that T-MPs activate a lysosomal pathway that is required for DCs presenting tumor antigens of T-MPs. DCs endocytose T-MPs to lysosomes, where T-MPs increase lysosomal pH from 5.0 to a peak of 8.5 via NOX2-catalyzed reactive oxygen species (ROS) production. This increased pH, coupled with T-MP–driven lysosomal centripetal migration, promotes the formation of MHC class I–tumor antigen peptide complexes. Concurrently, endocytosis of T-MPs results in the upregulation of CD80 and CD86. T-MP–increased ROS activate lysosomal Ca2+ channel Mcoln2, leading to Ca2+ release. Released Ca2+ activates transcription factor EB (TFEB), a lysosomal master regulator that directly binds to CD80 and CD86 promoters, promoting gene expression. These findings elucidate a pathway through which DCs efficiently present tumor antigen from T-MPs to CD8+ T cells, potentiating T-MPs as a novel tumor cell–free vaccine with clinical applications. Cancer Immunol Res; 6(9); 1057–68. ©2018 AACR.
Response to Immune Checkpoint Inhibition in Two Patients with Alveolar Soft-Part Sarcoma
Authors: Lewin Jeremy , Davidson Scott , Anderson Nathaniel D. , Lau Beatrice Y. , Kelly Jacalyn , Tabori Uri , Salah Samer , Butler Marcus O. , Aung Kyaw L. , Shlien Adam , Dickson Brendan C. , Abdul Razak Albiruni R.
Published: July 2018

Alveolar soft-part sarcoma (ASPS) is a morphologically distinctive mesenchymal tumor characterized by a canonical ASPL–TFE3 fusion product. In the metastatic setting, standard cytotoxic chemotherapies are typically ineffective. Studies have suggested modest clinical response to multitargeted receptor tyrosine kinase inhibitors. Here, we report sustained partial responses in two patients with immune checkpoint inhibition treated with either durvalumab (anti–PD-L1) alone or in combination with tremelimumab (anti–CTLA-4), which appeared unrelated to tumor immune infiltrates or mutational burden. Genomic analysis of these patients, and other cases of ASPS, demonstrated molecular mismatch-repair deficiency signatures. These findings suggest that immune checkpoint blockade may be a useful therapeutic strategy for ASPS. Cancer Immunol Res; 6(9); 1001–7. ©2018 AACR.
Expanded CD56superbrightCD16+ NK Cells from Ovarian Cancer Patients Are Cytotoxic against Autologous Tumor in a Patient-Derived Xenograft Murine Model
Authors: Poznanski Sophie M. , Nham Tina , Chew Marianne V. , Lee Amanda J. , Hammill Joanne A. , Fan Isabella Y. , Butcher Martin , Bramson Jonathan L. , Lee Dean A. , Hirte Hal W. , Ashkar Ali A.
Published: July 2018

Natural killer (NK) cells are useful for cancer immunotherapy and have proven clinically effective against hematologic malignancies. However, immunotherapies for poor prognosis solid malignancies, including ovarian cancer, have not been as successful due to immunosuppression by solid tumors. Although rearming patients' own NK cells to treat cancer is an attractive option, success of that strategy is limited by the impaired function of NK cells from cancer patients and by inhibition by self-MHC. In this study, we show that expansion converts healthy donor and immunosuppressed ovarian cancer patient NK cells to a cytotoxic CD56superbrightCD16+ subset with activation state and antitumor functions that increase with CD56 brightness. We investigated whether these expanded NK cells may overcome the limitations of autologous NK cell therapy against solid tumors. Peripheral blood- and ascites-derived NK cells from ovarian cancer patients were expanded and then adoptively transferred into cell-line and autologous patient-derived xenograft models of human ovarian cancer. Expanded ovarian cancer patient NK cells reduced the burden of established tumors and prolonged survival. These results suggest that CD56bright NK cells harbor superior antitumor function compared with CD56dim cells. Thus, NK cell expansion may overcome limitations on autologous NK cell therapy by converting the patient's NK cells to a cytotoxic subset that exerts a therapeutic effect against autologous tumor. These findings suggest that the value of expanded autologous NK cell therapy for ovarian cancer and other solid malignancies should be clinically assessed. Cancer Immunol Res; 6(10); 1174–85. ©2018 AACR.
ОСОБЛИВОСТІ ПІСЛЯДИПЛОМНОЇ ОСВІТИ КРАЇН ПОСТРАДЯНСЬКОГО ПРОСТОРУ
Authors: Sichkoriz O. Y.
Published: July 2018

Мета: аналіз особливостей становлення медичної та фармацевтичної післядипломної освіти в країнах пострадянського простору.Матеріали і методи. У роботі проведено ретроспективний аналіз розвитку післядипломної освіти в пострадянському просторі. Для розбору використано аналітико-описовий метод вивчення й узагальнення теорії та досвіду навчання у вищих навчальних закладах, критичний аналіз наукової літератури з педагогіки та методики навчання за темою дослідження.Результати. У роботі окреслено основні етапи розвитку післядипломної освіти у пострадянських країнах, висвітлено різницю післядипломної медичної освіти Росії та інших держав на сьогодні та проведено порівняння їх з міжнародними та європейськими моделями. Відображено, що післядипломна медична та фармацевтична освіта у пострадянських республіках перебуває в стані розбудови та реформування.Висновки. У розробці нових систем-моделей післядипломної освіти не достатньо враховано національні особливості та традиції країн пострадянського простору та використано далеко не всі можливості загальноприйнятих стандартизованих європейських і світових моделей безперервної медичної та фармацевтичної освіти.
ПРИХИЛЬНІСТЬ ДО ДОВГОТРИВАЛОЇ ВТОРИННОЇ ПРОФІЛАКТИКИ ПІСЛЯ ІНФАРКТУ МІОКАРДА
Authors: Hrebenyk M. V. , Levchyk I. V.
Published: July 2018

Мета: оцінити прихильність до довготривалого лікування хворих після інфаркту міокарда (ІМ) залежно від реваскуляризації.Матеріали і методи. Обстежено 152 хворих із інфарктом міокарда, яких поділено на групи: 1а – прихильні (за анкетуванням Morisky-Green), із перкутанним коронарним втручанням (ПКВ) (n=47), 1б – прихильні, без ПКВ (n=30); 2а – не прихильні, із ПКВ (n=25), 2б – не прихильні, без ПКВ (n=50). Оцінювали зміни клініко-лабораторних та ехокардіографічних значень.Результати. У всіх хворих не зменшувався індекс маси тіла, а 2/3 курять і досі. Серед осіб 1а групи, на відміну від решти груп, знижувались частота серцевих скорочень (ЧСС), систолічний та діастолічний артеріальний тиск (САТ та ДАТ), глюкоза та холестерол, і через 24 місяці зміни утримувались. Також у них достовірно змінювалась геометрія серця.Висновки. Після ІМ зберігається частковий комплаєнс. У цих пацієнтів встановлено дуже низьку прихильність до немедикаментозних методів вторинної профілактики та заходів із корекції факторів ризику і модифікації стилю життя, що зумовлює необхідність оптимізації організаційно-профілактичних заходів на амбулаторному етапі.
ІНФОРМАЦІЙНЕ ЗАБЕЗПЕЧЕННЯ СФЕРИ ОХОРОНИ ЗДОРОВ’Я УКРАЇНИ ПРОДУКЦІЄЮ, ОТРИМАНОЮ ПРИ ВИКОНАННІ НАУКОВИХ РОЗРОБОК УСТАНОВАМИ ГАЛУЗІ У 2014–2016 рр.
Authors: Zakrutko L. I. , Gorban Ye. M. , Bilan L. G. , Movchun N. O.
Published: July 2018

Мета: дослідити інформаційне забезпечення сфери охорони здоров’я України продукцією, отриманою при виконанні наукових розробок установами галузі у 2014–2016 рр.Матеріали і методи. Проведено ретроспективний аналіз реєстрів галузевих нововведень, переліку наукової (науково-технічної) продукції, призначеної для впровадження досягнень медичної науки у сферу охорони здоров’я, звітів установ щодо моніторингу впровадження наукової (науково-технічної) продукції протягом 2014–2016 років з моменту її створення.Результати. За період 2014–2016 рр. переважну більшість нововведень для впровадження у сферу охорони здоров’я було запропоновано ВМНЗ галузі. Кваліметрична характеристика нововведень за назвою лікарської (провізорської) спеціальності у 2016 р. показала, що високе кількісне співвідношення припадає на 10 спеціальностей (22,2 % від загальної кількості проаналізованих спеціальностей). Найбільше запропоновано у 2016 р. нові способи лікування (34,8 %) та нові способи діагностики (28,1 %) серед загальної кількості нововведень.Висновки. Результати аналізу щорічної динаміки запропонованих для впровадження в практику охорони здоров’я України інновацій протягом 2014–2016 рр. свідчить, що за рядом напрямів розробки відповідають нагальним пріоритетам сфери охорони здоров’я.
Iron Overload Exacerbates the Risk of Hemorrhagic Transformation After tPA (Tissue-Type Plasminogen Activator) Administration in Thromboembolic Stroke Mice
Authors: García-Yébenes Isaac , García-Culebras Alicia , Peña-Martínez Carolina , Fernández-López David , Díaz-Guzmán Jaime , Negredo Pilar , Avendaño Carlos , Castellanos Mar , Gasull Teresa , Dávalos Antoni , Moro María A. , Lizasoain Ignacio
Published: July 2018

Background and Purpose—

Recanalization with tPA (tissue-type plasminogen activator) is the only pharmacological therapy available for patients with ischemic stroke. However, the percentage of patients who may receive this therapy is limited by the risk of hemorrhagic transformation (HT)—the main complication of ischemic stroke. Our aim is to establish whether iron overload affects HT risk, to identify mechanisms that could help to select patients and to prevent this devastating complication.

Methods—

Mice fed with control or high-iron diet were subjected to thromboembolic stroke, with or without tPA therapy at different times after occlusion. Blood samples were collected for determination of malondialdehyde, matrix metalloproteinases, and fibronectin. Brain samples were collected 24 hours after occlusion to determine brain infarct and edema size, hemorrhage extension, IgG extravasation, and inflammatory and oxidative markers (neutrophil infiltration, 4-hydroxynonenal, and matrix metalloproteinase-9 staining).

Results—

Despite an increased rate of recanalization, iron-overload mice showed less neuroprotection after tPA administration. Importantly, iron overload exacerbated the risk of HT after early tPA administration, accelerated ischemia-induced serum matrix metalloproteinase-9 increase, and enhanced basal serum lipid peroxidation. High iron increased brain lipid peroxidation at most times and neutrophil infiltration at the latest time studied.

Conclusions—

Our data showing that iron overload increases the death of the compromised tissues, accelerates the time of tPA-induced reperfusion, and exacerbates the risk of HT may have relevant clinical implications for a safer thrombolysis. Patients with stroke with iron overload might be at high risk of HT after fibrinolysis, and, therefore, clinical studies must be performed to confirm our results.
When Neglect Isn’t Working Anymore: The Unlikely Success of the Tuxedo Party
Authors: Cronin Keri , Fowler Tim , Hagar Douglas
Published: July 2018

In 2012, Tuxedo Stan, a domestic long-hair cat, “ran for mayor” of Halifax, Nova Scotia, and a year later Stan’s brother, Earl Grey, “ran for premier” of Nova Scotia. What separated Stan and Earl Grey (who ran under the banner of the Tuxedo Party) from other politically minded felines was that the Tuxedo Party campaigns were not stunt or joke campaigns. While the cats could obviously not take office, the two campaigns were nonetheless political advocacy campaigns, with a clearly articulated message to make life better for feral and stray cats. This paper argues that the Tuxedo Party successfully elevated the issue onto the political agenda through their savvy mix of social media, and the use of positive imagery of cats in their campaigns.