bluuebunny/crossref_metadata_2025_split huggingface dataset:
Learning from the other limb's experience: sharing the ‘trained’ M1 representation of the motor sequence knowledge
Authors: Gabitov Ella , Manor David , Karni Avi 
Published: October 2015

Key points
Participants were scanned during the untrained‐hand performance of a motor sequence, intensively trained a day earlier, and also a similarly constructed but novel, untrained sequence.
The superior performance levels for the trained, compared to the untrained sequence, were associated with a greater magnitude of activity within the primary motor cortex (M1), bilaterally, for the trained sequence.
The differential responses in the ‘trained’ M1, ipsilateral to the untrained hand, were positively correlated with experience‐related differences in the functional connectivity between the ‘trained’ M1 and (1) its homologue and (2) the dorsal premotor cortex (PMd) within the contralateral hemisphere.
No significant correlation was evident between experience‐related differences in M1 – M1 and M1 – PMd connectivity measures.
These results suggest that the transfer of sequence‐specific information between the two primary motor cortices is predominantly mediated by excitatory mechanisms driven by the ‘trained’ M1 via two independent neural pathways.
AbstractFollowing unimanual training on a novel sequence of movements, sequence‐specific performance may improve overnight not only in the trained hand, but also in the hand afforded no actual physical experience. It is not clear, however, how transfer to the untrained hand is achieved. In the present study, we examined whether and how interaction between the two primary motor cortices contributes to the performance of a sequence of movements, extensively trained the day before, by the untrained hand. Acordingly, we studied participants during the untrained‐hand performance of a finger‐to‐thumb opposition sequence (FOS), intensively trained a day earlier (T‐FOS), and a similarly constructed, but novel, untrained FOS (U‐FOS). Changes in neural signals driven by task performance were assessed using functional magnetic resonance imaging. To minimize potential differences as a result of the rate of sequence execution per se, participants performed both sequences at an identical paced rate. The analyses showed that the superior fluency in executing the T‐FOS compared to the U‐FOS was associated with higher activity within the primary motor cortex (M1), bilaterally, for the T‐FOS. The differential responses in the ‘trained’ M1 were positively correlated with experience‐related differences in the functional connectivity between the ‘trained’ M1 and (1) its left homologue and (2) the left dorsal premotor cortex. However, no significant correlation was evident between the changes in connectivity in these two routes. These results suggest that the transfer of sequence‐specific information between the two primary motor cortices is predominantly mediated by excitatory mechanisms driven by the ‘trained’ M1 via at least two independent neural pathways.
Ischaemic concentrations of lactate increase TREK1 channel activity by interacting with a single histidine residue in the carboxy terminal domain
Authors: Ghatak Swagata , Banerjee Aditi , Sikdar Sujit Kumar 
Published: October 2015

Key points
The physiological metabolite, lactate and the two‐pore domain leak potassium channel, TREK1 are known neuroprotectants against cerebral ischaemia. However, it is not known whether lactate interacts with TREK1 channel to provide neuroprotection.
In this study we show that lactate increases TREK1 channel activity and hyperpolarizes CA1 stratum radiatum astrocytes in hippocampal slices.
Lactate increases open probability and decreases longer close time of the human (h)TREK1 channel in a concentration dependent manner.
Lactate interacts with histidine 328 (H328) in the carboxy terminal domain of hTREK1 channel to decrease its dwell time in the longer closed state. This interaction was dependent on the charge on H328.
Lactate‐insensitive mutant H328A hTREK1 showed pH sensitivity similar to wild‐type hTREK1, indicating that the effect of lactate on hTREK1 is independent of pH change.
AbstractA rise in lactate concentration and the leak potassium channel TREK1 have been independently associated with cerebral ischaemia. Recent literature suggests lactate to be neuroprotective and TREK1 knockout mice show an increased sensitivity to brain and spinal cord ischaemia; however, the connecting link between the two is missing. Therefore we hypothesized that lactate might interact with TREK1 channels. In the present study, we show that lactate at ischaemic concentrations (15–30 mm) at pH 7.4 increases TREK1 current in CA1 stratum radiatum astrocytes and causes membrane hyperpolarization. We confirm the intracellular action of lactate on TREK1 in hippocampal slices using monocarboxylate transporter blockers and at single channel level in cell‐free inside‐out membrane patches. The intracellular effect of lactate on TREK1 is specific since other monocarboxylates such as pyruvate and acetate at pH 7.4 failed to increase TREK1 current. Deletion and point mutation experiments suggest that lactate decreases the longer close dwell time incrementally with increase in lactate concentration by interacting with the histidine residue at position 328 (H328) in the carboxy terminal domain of the TREK1 channel. The interaction of lactate with H328 is dependent on the charge on the histidine residue since isosteric mutation of H328 to glutamine did not show an increase in TREK1 channel activity with lactate. This is the first demonstration of a direct effect of lactate on ion channel activity. The action of lactate on the TREK1 channel signifies a separate neuroprotective mechanism in ischaemia since it was found to be independent of the effect of acidic pH on channel activity.
Technical Note: Motion‐perturbation method applied to dosimetry of dynamic MLC target tracking—A proof‐of‐concept
Authors: Feygelman Vladimir , Tonner Brian , Stambaugh Cassandra , Hunt Dylan , Zhang Geoffrey , Moros Eduardo , Nelms Benjamin E. 
Published: October 2015

Purpose:Previous studies show that dose to a moving target can be estimated using 4D measurement‐guided dose reconstruction based on a process called virtual motion simulation, or VMS. A potential extension of VMS is to estimate dose during dynamic multileaf collimator (MLC)‐tracking treatments. The authors introduce a modified VMS method and quantify its performance as proof‐of‐concept for tracking applications.Methods:Direct measurements with a moving biplanar diode array were used to verify accuracy of the VMS dose estimates. A tracking environment for variably sized circular MLC apertures was simulated by sending preprogrammed control points to the MLC while simultaneously moving the accelerator treatment table. Sensitivity of the method to simulated tracking latency (0–700 ms) was also studied. Potential applicability of VMS to fast changing beam apertures was evaluated by modeling, based on the demonstrated dependence of the cumulative dose on the temporal dose gradient.Results:When physical and virtual latencies were matched, the agreement rates (2% global/2 mm gamma) between the VMS and the biplanar dosimeter were above 96%. When compared to their own reference dose (0 induced latency), the agreement rates for VMS and biplanar array track closely up to 200 ms of induced latency with 10% low‐dose cutoff threshold and 300 ms with 50% cutoff. Time‐resolved measurements suggest that even in the modulated beams, the error in the cumulative dose introduced by the 200 ms VMS time resolution is not likely to exceed 0.5%.Conclusions:Based on current results and prior benchmarks of VMS accuracy, the authors postulate that this approach should be applicable to any MLC‐tracking treatments where leaf speeds do not exceed those of the current Varian accelerators.
Sphingosine Kinase Regulates Microtubule Dynamics and Organelle Positioning Necessary for Proper G
1
/S Cell Cycle Transition in Trypanosoma brucei
Authors: Pasternack Deborah A. , Sharma Aabha I. , Olson Cheryl L. , Epting Conrad L. , Engman David M. 
Published: October 2015

ABSTRACT

Sphingolipids are important constituents of cell membranes and also serve as mediators of cell signaling and cell recognition. Sphingolipid metabolites such as sphingosine-1-phosphate and ceramide regulate signaling cascades involved in cell proliferation and differentiation, autophagy, inflammation, and apoptosis. Little is known about how sphingolipids and their metabolites function in single-celled eukaryotes. In the present study, we investigated the role of sphingosine kinase (SPHK) in the biology of the protozoan parasite
Trypanosoma brucei
, the agent of African sleeping sickness.
T. brucei
SPHK (TbSPHK) is constitutively but differentially expressed during the life cycle of
T. brucei
. Depletion of TbSPHK in procyclic-form
T. brucei
causes impaired growth and attenuation in the G
1
/S phase of the cell cycle. TbSPHK-depleted cells also develop organelle positioning defects and an accumulation of tyrosinated α-tubulin at the elongated posterior end of the cell, known as the “nozzle” phenotype, caused by other molecular perturbations in this organism. Our studies indicate that TbSPHK is involved in G
1
-to-S cell cycle progression, organelle positioning, and maintenance of cell morphology. Cytotoxicity assays using TbSPHK inhibitors revealed a favorable therapeutic index between
T. brucei
and human cells, suggesting TbSPHK to be a novel drug target.

IMPORTANCE
Trypanosoma brucei
is a single-celled parasite that is transmitted between humans and other animals by the tsetse fly.
T. brucei
is endemic in sub-Saharan Africa, where over 70 million people and countless livestock are at risk of developing
T. brucei
infection, called African sleeping sickness, resulting in economic losses of ~$35 million from the loss of cattle alone. New drugs for this infection are sorely needed and scientists are trying to identify essential enzymes in the parasite that can be targets for new therapies. One possible enzyme target is sphingosine kinase, an enzyme involved in the synthesis of lipids important for cell surface integrity and regulation of cell functions. In this study, we found that sphingosine kinase is essential for normal growth and structure of the parasite, raising the possibility that it could be a good target for new chemotherapy for sleeping sickness.
Is It Possible? A Different Approach to Creating a Universal Influenza Vaccine
Authors: Schultz-Cherry Stacey 
Published: October 2015

ABSTRACT
The best way to combat influenza virus infection is to prevent it. However, the continual evolution of circulating influenza virus strains and the constant threat of newly emerging viruses forces the public health community to annually update seasonal influenza vaccines while stockpiling potential pandemic virus vaccines. Thus, there is an urgent need to develop a “universal” influenza vaccine that affords protection against all strains. In their recent article, L. M. Schwartzman et al. (mBio 6:e01044-15, 2015, doi:10.1128/mBio.01044-15) demonstrated that intranasal immunization of mice with a cocktail of viral-like particles (VLPs) expressing distinct influenza virus hemagglutinin (HA) proteins can broadly protect against infection not only with the same viral strains but also with unrelated strains. These findings suggest a promising strategy for developing a broadly protective “universal” influenza vaccine.
Musculoskeletal pain and limitations in work ability in Swedish marines: a cross-sectional survey of prevalence and associated factors
Authors: Monnier Andreas , Larsson Helena , Djupsjöbacka Mats , Brodin Lars-Åke , Äng Björn O 
Published: October 2015

ObjectivesTo estimate the prevalence of self-rated musculoskeletal pain and pain limiting work ability in Swedish Armed Forces (SAF) marines, and to study factors potentially associated with pain limiting work ability for the most prevalent pain regions reported.DesignPopulation-based, cross-sectional survey.ParticipantsThere were 272 SAF marines from the main marine battalion in Sweden included in the study.OutcomesSelf-assessed musculoskeletal pain and pain limiting the marines' work ability within a 6-month period, as obtained from structured questionnaires. The association of individual, health and work-related factors with musculoskeletal pain limiting work ability was systematically regressed with multiple logistic models, estimating OR and 95% CI.ResultsMusculoskeletal pain and pain limiting work ability were most common in the back, at 46% and 20%, and lower extremities at 51% and 29%, respectively. Physical training ≤1 day/week (OR 5.3, 95% CI 1.7 to 16.8); body height ≤1.80 m (OR 5.0, 95% CI 1.6 to 15.1) and ≥1.86 m (OR 4.4, 95% CI 1.4 to 14.1); computer work 1/4 of the working day (OR 3.2, 95% CI 1.0 to 10.0) and ≥1/2 (OR 3.3, 95% CI 1.1 to 10.1) of the working day were independently associated with back pain limiting work ability. None of the studied variables emerged significantly associated with such pain for the lower extremities.ConclusionsOur findings show that musculoskeletal pain and resultant limitations in work ability are common in SAF marines. Low frequency of physical training emerged independently associated with back pain limiting work ability. This suggests that marines performing physical training 1 day per week or less are suitable candidates for further medical evaluation and secondary preventive actions. While also associated, body height and computer work need further exploration as underlying mechanisms for back pain limiting work ability. Further prospective studies are necessary to clarify the direction of causality.
Pregnancy-related venous thrombosis: comparison between spontaneous and ART conception in an Italian cohort
Authors: Villani Michela , Dentali Francesco , Colaizzo Donatella , Tiscia Giovanni Luca , Vergura Patrizia , Petruccelli Tiziana , Petruzzelli Francesco , Ageno Walter , Margaglione Maurizio , Grandone Elvira 
Published: October 2015

ObjectiveTo evaluate in an Italian cohort the incidence of venous thromboembolic events (VTE) in pregnancies after assisted reproductive technologies (ART).SettingThrombosis and Haemostasis Unit at I.R.C.C.S. ‘Casa Sollievo della Sofferenza’, S. Giovanni Rotondo.ParticipantsA prospective cohort of 998 women advised to undergo ART was referred by local fertility clinics from April 2002 to July 2011. Follow-up information was obtained during the check-up and/or by phone interviews. In a cohort of women who consecutively gave birth (n=3339) after spontaneous conception in our Institution, information on the diagnoses of pregnancy-related venous thromboses was obtained by linkage to a patient administrative register.Primary and secondary outcome measuresWe calculated the incidence of VTE and superficial venous thrombosis in successful ART cycles and compared it with that of the general population conceiving spontaneously.ResultsOverall, 684 ART cycles were carried out by 234 women, who achieved a clinical pregnancy; in case of more than one successful cycle, only the first pregnancy was considered. Three vein thromboses (two VTE and one superficial vein thrombosis) were recorded. An antithrombotic prophylaxis with LMWH alone or combined with low-dose aspirin was prescribed in 23/234 (9.8%) women. In the reference cohort of 3339 women, a total of 11 vein thromboses were observed: six VTE and five SVT. The two-tailed Fisher exact test showed a trend towards statistical significance (p: 0.06, OR: 3.9, 95% CI 0.87 to 15.3). After the exclusion of superficial thromboses in both the groups, we found that the incidence of VTE in our population of women who had undergone ART was 2/234 pregnancies (8.5 ‰), whereas that in our reference population was 6/3339 (1.8 ‰) (p: 0.09).ConclusionsOur data show a slightly higher incidence of vein thromboses in pregnancies after ART than in those after natural conception.
Study protocol for a controlled trial of Strengths Model Case Management in mental health services in Hong Kong
Authors: Tsoi Wing-See Emily , Tse Samson , Fukui Sadaaki , Jones Steven 
Published: October 2015

IntroductionAlthough strengths-based models are popular within recovery-oriented approaches, there is still a lack of conclusive research to guide how they should be implemented. A recent meta-analysis confirmed the lack of clarity in how this perspective is operationalised and that fidelity monitoring during the implementation process is lacking. Hence, there is a clear need to evaluate the feasibility of delivering and evaluating a clearly operationalised strengths-based intervention that incorporates fidelity checks to inform more definitive research. This protocol therefore describes a controlled trial of Strengths Model Case Management (SMCM), a complex intervention, for people with severe mental illnesses in Hong Kong. This trial follows the guidelines of the Medical Research Council as a phase 2 trial. Hence, it is a pilot study that tests the feasibility and effectiveness of the model.Methods and analysisThis is a 9-month controlled trial that uses the Kansas Model. Participants and a matched control group are recruited on a voluntary basis, after screening for eligibility. Effectiveness of the SMCM will be measured through outcome measures taken at baseline, the mid-point and at the end of the trial. Outcomes for service users include personal recovery, hope, subjective well-being, psychiatric symptoms, perceived level of recovery features within the organisation, therapeutic alliance and achievement of recovery goals. Outcomes for care workers will include job burnout, organisational features of recovery and perceived supervisory support. With a 2×3 analysis of variance design and a moderate intervention effect (Cohen's d=0.50), a total of 86 participants will be needed for a statistical power of 0.80.Ethics and disseminationEthical approval has been obtained from the Human Research Ethics Committee for Non-Clinical Faculties at The University of Hong Kong (HRECNCF: EA140913).Trial registration numberAustralian New Zealand Clinical Trial Registry (ACTRN)12613001120763.
Simulation-based multiprofessional obstetric anaesthesia training conducted in situ versus off-site leads to similar individual and team outcomes: a randomised educational trial
Authors: Sørensen Jette Led , van der Vleuten Cees , Rosthøj Susanne , Østergaard Doris , LeBlanc Vicki , Johansen Marianne , Ekelund Kim , Starkopf Liis , Lindschou Jane , Gluud Christian , Weikop Pia , Ottesen Bent 
Published: October 2015

ObjectiveTo investigate the effect of in situ simulation (ISS) versus off-site simulation (OSS) on knowledge, patient safety attitude, stress, motivation, perceptions of simulation, team performance and organisational impact.DesignInvestigator-initiated single-centre randomised superiority educational trial.SettingObstetrics and anaesthesiology departments, Rigshospitalet, University of Copenhagen, Denmark.Participants100 participants in teams of 10, comprising midwives, specialised midwives, auxiliary nurses, nurse anaesthetists, operating theatre nurses, and consultant doctors and trainees in obstetrics and anaesthesiology.InterventionsTwo multiprofessional simulations (clinical management of an emergency caesarean section and a postpartum haemorrhage scenario) were conducted in teams of 10 in the ISS versus the OSS setting.Primary outcomeKnowledge assessed by a multiple choice question test.Exploratory outcomesIndividual outcomes: scores on the Safety Attitudes Questionnaire, stress measurements (State-Trait Anxiety Inventory, cognitive appraisal and salivary cortisol), Intrinsic Motivation Inventory and perceptions of simulations. Team outcome: video assessment of team performance. Organisational impact: suggestions for organisational changes.ResultsThe trial was conducted from April to June 2013. No differences between the two groups were found for the multiple choice question test, patient safety attitude, stress measurements, motivation or the evaluation of the simulations. The participants in the ISS group scored the authenticity of the simulation significantly higher than did the participants in the OSS group. Expert video assessment of team performance showed no differences between the ISS versus the OSS group. The ISS group provided more ideas and suggestions for changes at the organisational level.ConclusionsIn this randomised trial, no significant differences were found regarding knowledge, patient safety attitude, motivation or stress measurements when comparing ISS versus OSS. Although participant perception of the authenticity of ISS versus OSS differed significantly, there were no differences in other outcomes between the groups except that the ISS group generated more suggestions for organisational changes.Trial registration numberNCT01792674.
Pattern of cardiac surveillance among patients with lymphoma receiving anthracycline-based chemotherapy
Authors: Hung Olivia Y , Brown Jennifer R , Dai Tian , Easley Kirk A , Flowers Christopher R , Parashar Susmita 
Published: October 2015

ObjectiveAnthracyclines are potent antineoplastic agents in the treatment of lymphoid malignancies, but their therapeutic benefit is limited by cardiotoxicity. The American Heart Association (AHA) recommends routine surveillance, early diagnosis and treatment of anthracycline-based chemotherapy (AC) induced cardiomyopathy (AC-CMP). We aimed to assess the prevalence of AC-CMP in patients with lymphoma, surveillance patterns of left ventricular ejection fraction (LVEF) in those receiving AC and management of patients with AC-CMP at an academic medical centre prior to the development of a comprehensive cardio-oncology programme.MethodsWe performed a retrospective cohort study examining 218 patients with aggressive B cell non-Hodgkin's lymphomas (B-NHL) who received AC 1992–2012 and had serial follow-up. AC-CMP was defined as LVEF decrease ≥10% with final LVEF≤50% or LVEF reduction ≥15% regardless of final LVEF.ResultsOf 218 patients treated with AC, 73 (34%) had LVEF assessment both prior to and after receiving AC. Of these 73 patients, 24 developed AC-CMP and had higher cumulative all-cause mortality than those without AC-CMP (HR 2.35, p=0.03). Coronary artery disease (CAD) was an independent predictor of AC-CMP (p=0.048). Mean post-AC LVEF was lower in patients with CAD compared with those without CAD when their baseline LVEF was 45% (p=0.0009) or 55% (p=0.001) but was similar at 65% (p=0.33). Less than half of patients with AC-CMP received recommended heart failure medication therapy.ConclusionsHistorically, one-third of patients with B-NHL treated with AC underwent surveillance according to AHA guidelines. There is substantial opportunity for collaboration between oncologists and cardiologists to improve the care of patients with lymphoma receiving AC.