bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sitting less elicits metabolic responses similar to exercise and enhances insulin sensitivity in postmenopausal women
Authors: Remie Carlijn M. E. , Janssens Georges E. , Bilet Lena , van Weeghel Michel , Duvivier Bernard M. F. M. , de Wit Vera H. W. , Connell Niels J. , Jörgensen Johanna A. , Schomakers Bauke V. , Schrauwen-Hinderling Vera B. , Hoeks Joris , Hesselink Matthijs K. C. , Phielix Esther , Houtkooper Riekelt H. , Schrauwen Patrick 
Published: September 2021

Abstract
Aims/hypothesis
In our current society sedentary behaviour predominates in most people and is associated with the risk of developing type 2 diabetes. It has been suggested that replacing sitting time by standing and walking could be beneficial for individuals with type 2 diabetes but the underlying mechanisms are unknown and direct comparisons with exercise are lacking. Our objective was to directly compare metabolic responses of either sitting less or exercising, relative to being sedentary.

Methods
We performed a randomised, crossover intervention study in 12 overweight women who performed three well-controlled 4 day activity regimens: (1) sitting regimen (sitting 14 h/day); (2) exercise regimen (sitting 13 h/day, exercise 1 h/day); and (3) sitting less regimen (sitting 9 h/day, standing 4 h/day and walking 3 h/day). The primary outcome was insulin sensitivity measured by a two-step hyperinsulinaemic–euglycaemic clamp. We additionally performed metabolomics on muscle biopsies taken before the clamp to identify changes at the molecular level.

Results
Replacing sitting time by standing and walking over 4 days resulted in improved peripheral insulin sensitivity, comparable with the improvement achieved by moderate-to-vigorous exercise. Specifically, we report a significant improvement in peripheral insulin sensitivity in the sitting less (~13%) and the exercise regimen (~20%), compared with the sitting regimen. Furthermore, sitting less shifted the underlying muscle metabolome towards that seen with moderate-to-vigorous exercise, compared with the sitting regimen.

Conclusions/interpretations
Replacing sitting time by standing and walking is an attractive alternative to moderate-to-vigorous exercise for improving metabolic health.

Trial registration
ClinicalTrials.gov NCT03912922.

Graphical abstract
Good clinical outcomes after patellar cartilage repair with no evidence for inferior results in complex cases with the need for additional patellofemoral realignment procedures: a systematic review
Authors: Burger Daniel , Feucht Matthias , Muench Lukas N. , Forkel Philipp , Imhoff Andreas B. , Mehl Julian 
Published: September 2021

Abstract
Purpose
Focal, patellar cartilage defects are a challenging problem as most cases have an underlying multifactorial pathogenesis. This systematic review of current literature analysed clinical results after regenerative cartilage repair of the patella with a special focus on the assessment and treatment of existing patellofemoral malalignment.

Methods
A systematic review was conducted to identify articles reporting clinical results after cartilage regenerative surgeries of the patella using the PubMed and Scopus database. The extracted data included patient-reported outcome measures (PROMS) and whether cartilage repair was performed alone or in combination with concomitant surgeries of underlying patellofemoral co-pathologies. In cases of isolated cartilage repair, specific exclusion criteria regarding underlying co-pathologies were screened. In cases of concomitant surgeries, the type of surgeries and their specific indications were extracted.

Results
A total of 35 original articles were included out of which 27 (77%) were cohort studies with level IV evidence. The most frequently used technique for cartilage restoration of the patella was autologous chondrocyte implantation (ACI). Results after isolated cartilage repair alone were reported by 15 (43%) studies. Of those studies, 9 (60%) excluded patients with underlying patellofemoral malalignment a priori and 6 (40%) did not analyse underlying co-pathologies at all. Among the studies including combined surgeries, the most frequently reported concomitant procedures were release of the lateral retinaculum, reconstruction of the medial patellofemoral ligament (MPFL), and osteotomy of the tibial tubercle. In summary, these studies showed lower preoperative PROMS but similar final PROMS in comparison with the studies reporting on isolated cartilage repair. The most frequently used PROMS were the IKDC-, Lysholm- and the Modified Cincinnati Score.

Conclusion
This comprehensive literature review demonstrated good clinical outcomes after patellar cartilage repair with no evidence of minor results even in complex cases with the need for additional patellofemoral realignment procedures. However, a meaningful statistical comparison between isolated patellar cartilage repair and combined co-procedures is not possible due to very heterogeneous patient cohorts and a lack of analysis of specific subgroups in recent literature.

Level of evidence
Level IV.
New insights on manipulating the material removal characteristics of Jet-Electrochemical machining through nozzle design
Authors: Kendall Thomas , Diver Carl , Gillen David , Bartolo Paulo 
Published: September 2021

AbstractJet-Electrochemical machining (Jet-ECM) is a novel variation of traditional electrochemical machining in which electrically conductive material is removed through anodic dissolution by means of a fine jet of electrolyte. In this study, the effect of nozzle geometry on material removal characteristics are investigated through physical experiments performed on a Jet-ECM system under development at the university of Manchester. A total of 8 nozzles with holes encompassing converging, diverging and rounded features are studied at flow rates between 0.125 and 0.225 l/min. The results show that the nozzle hole geometry has a significant effect on the machined profile produced due to variations in flow velocity, pressure, and electric current distribution with converging hole nozzles providing an increased depth of cut than the symmetrical cylindrical channel by up to 9.7%. A 2D Star CCM+ simulation is also proposed, and numerical results developed and compared with experimental ones to investigate the feasibility of using simulation to develop future nozzle designs. The simulated results show good profile comparison to the experimental results, however, the model needs developing to improve the process repeatability for future use in nozzle design.
The importance of individual variation for the interpretation of behavioural studies: ethanol effects vary with basal activity level in zebrafish larvae
Authors: Davis Raissa , Luchtenburg Floris , Richardson Michael , Schaaf Marcel , Tudorache Christian , Slabbekoorn Hans 
Published: September 2021

AbstractStandardization and reduction of variation is key to behavioural screening of animal models in toxicological and pharmacological studies. However, individual variation in behavioural and physiological phenotypes remains in each laboratory population and can undermine the understanding of toxicological and pharmaceutical effects and their underlying mechanisms. Here, we used zebrafish (ABTL-strain) larvae to explore individual consistency in activity level and emergence time, across subsequent days of early development (6–8 dpf). We also explored the correlation between these two behavioural parameters. We found inter-individual consistency over time in activity level and emergence time, but we did not find a consistent correlation between these parameters. Subsequently, we investigated the impact of variation in activity level on the effect of a 1% ethanol treatment, suitable for our proof-of-concept case study about whether impact from pharmacological treatments might be affected by inter-individual variation in basal locomotion. The inter-individual consistency over time in activity level did not persist in this test. This was due to the velocity change from before to after exposure, which turned out to be a dynamic individual trait related to basal activity level: low-activity individuals raised their swimming velocity, while high-activity individuals slowed down, yielding diametrically opposite response patterns to ethanol exposure. We therefore argue that inter-individual consistency in basal activity level, already from 6 dpf, is an important factor to take into account and provides a practical measure to improve the power of statistical analyses and the scope for data interpretation from behavioural screening studies.
Turning Point Principle for Relativistic Stars
Authors: Hadžić Mahir , Lin Zhiwu 
Published: September 2021

AbstractUpon specifying an equation of state, spherically symmetric steady states of the Einstein-Euler system are embedded in 1-parameter families of solutions, characterized by the value of their central redshift. In the 1960’s Zel’dovich (Voprosy Kosmogonii 9:157–170, 1963) and Harrison et al. (Gravitation Theory and Gravitational Collapse. The University of Chicago press, Chicago, 1965) formulated a turning point principle which states that the spectral stability can be exchanged to instability and vice versa only at the extrema of mass along the mass-radius curve. Moreover the bending orientation at the extrema determines whether a growing mode is gained or lost. We prove the turning point principle and provide a detailed description of the linearized dynamics. One of the corollaries of our result is that the number of growing modes grows to infinity as the central redshift increases to infinity.
Enhancement of task-switching performance with transcranial direct current stimulation over the right lateral prefrontal cortex
Authors: Prehn Kristin , Skoglund Anja , Strobach Tilo 
Published: September 2021

AbstractSwitching between two or more tasks is a key component in our modern world. Task switching, however, requires time-consuming executive control processes and thus produces performance costs when compared to task repetitions. While executive control during task switching has been associated with activation in the lateral prefrontal cortex (lPFC), only few studies so far have investigated the causal relation between lPFC activation and task-switching performance by modulating lPFC activation. In these studies, the results of lPFC modulation were not conclusive or limited to the left lPFC. In the present study, we aimed to investigate the effect of non-invasive transcranial direct current stimulation [tDCS; anodal tDCS (1 mA, 20 min) vs. cathodal tDCS (1 mA, 20 min) vs. sham tDCS (1 mA, 30 s)] over the right inferior frontal junction on task-switching performance in a well-established task-switching paradigm. In response times, we found a significant effect of tDCS Condition (atDCS, ctDCS vs. sham) on task-switching costs, indicating the modulation of task-switching performance by tDCS. In addition, we found a task-unspecific tDCS Condition effect in the first experimental session, in which participants were least familiar with the task, indicating a general enhancement of task performance in both task repetitions and task-switching trials. Taken together, our study provides evidence that the right lPFC is involved in task switching as well as in general task processing. Further studies are needed to investigate whether these findings can be translated into clinically relevant improvement in older subjects or populations with executive function impairment.
Necrotizing Enterocolitis in Children with Congenital Heart Disease: A Literature Review
Authors: Kelleher Sean T. , McMahon Colin J. , James Adam 
Published: September 2021

AbstractInfants with congenital heart disease (CHD) are at an increased risk of developing necrotising enterocolitis (NEC), a serious inflammatory intestinal condition classically associated with prematurity. CHD not only increases the risk of NEC in preterm infants but is one of the most commonly implicated risk factors in term infants. Existing knowledge on the topic is limited largely to retrospective studies. This review acts to consolidate existing knowledge on the topic in terms of disease incidence, pathophysiology, risk factors, outcomes and the complex relationship between NEC and enteral feeds. Potential preventative strategies, novel biomarkers for NEC in this population, and the role of the intestinal microbiome are all explored. Numerous challenges exist in the study of this complex multifactorial disease which arise from the heterogeneity of the affected population and its relative scarcity. Nevertheless, its high related morbidity and mortality warrant renewed interest in identifying those infants most at risk and implementing strategies to reduce the incidence of NEC in infants with CHD.
Non-linear dielectric spectroscopy for detecting and evaluating structure-property relations in a P(VDF-TrFE-CFE) relaxor-ferroelectric terpolymer
Authors: Raman Venkatesan Thulasinath , Smykalla David , Ploss Bernd , Wübbenhorst Michael , Gerhard Reimund 
Published: September 2021

AbstractNon-linear dielectric spectroscopy (NLDS) is employed as an effective tool to study relaxation processes and phase transitions of a poly(vinylidenefluoride-trifluoroethylene-chlorofluoroethylene) (P(VDF-TrFE-CFE)) relaxor-ferroelectric (R-F) terpolymer in detail. Measurements of the non-linear dielectric permittivity$${\varepsilon _{2}^{'}}$$ε2′reveal peaks at 30 and 80$$\,^\circ$$∘C that cannot be identified in conventional dielectric spectroscopy. By combining the results from NLDS experiments with those from other techniques such as thermally stimulated depolarization and dielectric-hysteresis studies, it is possible to explain the processes behind the additional peaks. The former peak, which is associated with the mid-temperature transition, is found in all other vinylidene fluoride-based polymers and may help to understand the non-zero$$\varepsilon _\mathrm {2}^{'}$$ε2′values that are detected on the paraelectric phase of the terpolymer. The latter peak can also be observed during cooling of P(VDF-TrFE) copolymer samples at 100$$\,^\circ$$∘C and is due to conduction and space-charge polarization as a result of the accumulation of real charges at the electrode–sample interface.
Impaired pulmonary vasomotor control in exercising swine with multiple comorbidities
Authors: van de Wouw Jens , Steenhorst Jarno J. , Sorop Oana , van Drie Ruben W. A. , Wielopolski Piotr A. , Kleinjan Alex , Hirsch Alexander , Duncker Dirk J. , Merkus Daphne 
Published: September 2021

AbstractPulmonary hypertension is common in heart failure with preserved ejection fraction (HFpEF). Here, we tested the hypothesis that comorbidities [diabetes mellitus (DM, streptozotocin), hypercholesterolemia (HC, high-fat diet) and chronic kidney disease (CKD, renal microembolization)] directly impair pulmonary vasomotor control in a DM + HC + CKD swine model. 6 months after induction of DM + HC + CKD, pulmonary arterial pressure was similar in chronically instrumented female DM + HC + CKD (n = 19) and Healthy swine (n = 18). However, cardiac output was lower both at rest and during exercise, implying an elevated pulmonary vascular resistance (PVR) in DM + HC + CKD swine (153 ± 10 vs. 122 ± 9 mmHg∙L−1∙min∙kg). Phosphodiesterase 5 inhibition and endothelin receptor antagonism decreased PVR in DM + HC + CKD (− 12 ± 12 and − 22 ± 7 mmHg∙L−1∙min∙kg) but not in Healthy swine (− 1 ± 12 and 2 ± 14 mmHg∙L−1∙min∙kg), indicating increased vasoconstrictor influences of phosphodiesterase 5 and endothelin. Inhibition of nitric oxide synthase produced pulmonary vasoconstriction that was similar in Healthy and DM + HC + CKD swine, but unmasked a pulmonary vasodilator effect of endothelin receptor antagonism in Healthy (− 56 ± 26 mmHg∙L−1∙min∙kg), whereas it failed to significantly decrease PVR in DM + HC + CKD, indicating loss of nitric oxide mediated inhibition of endothelin in DM + HC + CKD. Scavenging of reactive oxygen species (ROS) had no effect on PVR in either Healthy or DM + HC + CKD swine. Cardiovascular magnetic resonance imaging, under anesthesia, showed no right ventricular changes. Finally, despite an increased contribution of endogenous nitric oxide to vasomotor tone regulation in the systemic vasculature, systemic vascular resistance at rest was higher in DM + HC + CKD compared to Healthy swine (824 ± 41 vs. 698 ± 35 mmHg∙L−1∙min∙kg). ROS scavenging induced systemic vasodilation in DM + HC + CKD, but not Healthy swine. In conclusion, common comorbidities directly alter pulmonary vascular control, by enhanced PDE5 and endothelin-mediated vasoconstrictor influences, well before overt left ventricular backward failure or pulmonary hypertension develop.
Outcome for sinonasal malignancies: a population-based survey
Authors: Hafström Anna , Sjövall Johanna , Persson Simon S. , Nilsson Johan S. , Svensson Christer , Brun Eva , Greiff Lennart 
Published: September 2021

Abstract
Purpose
Sinonasal malignancies (SNM) represent a rare and complex group of cancers that includes a wide range of histopathological subtypes. Data from population-based cohorts are scarce but warranted as a basis for randomized controlled treatment trials (RCTs). Our aim was to assess overall and histology subset-specific outcomes for SNM patients treated at a tertiary referral centre.

Methods
A retrospective, population-based, consecutive cohort of patients with SNMs diagnosed from 2001 through 2019 was examined. Outcome was analysed in relation to age, gender, site, stage, histopathology, and treatment.

Results
Two-hundred and twenty-six patients were identified, whereof 61% presented with stage IV disease. 80% completed treatment with curative intent, which comprised surgery with neoadjuvant (29%) or adjuvant (37%) radiotherapy, monotherapy with surgery (22%), definitive chemoradiotherapy (7%), or radiotherapy (5%). Median follow-up was 106 months. The 5- and 10-year overall survival rates were 57% and 35%, respectively. Median overall survival was 76 months (esthesioneuroblastoma: 147 months; adenocarcinoma: 117; salivary carcinoma: 88; mucosal melanoma: 69; squamous cell carcinoma: 51, undifferentiated carcinoma: 42; neuroendocrine carcinoma: 9; and NUT-carcinoma 5). The 5- and 10-year disease-free survival rates were 63% and 54%, respectively, and disease-specific survival 83% and 66%. Increasing age, stage IVB, melanoma histopathology, and treatment with definitive chemoradiotherapy emerged as significant independent prognostic risk factors for disease-specific mortality (p ≤ 0.001).

Conclusion
The results indicate a seemingly good outcome in comparison to previous reports, particularly for mucosal melanoma, adenocarcinoma, and undifferentiated carcinoma. The study provides additional background for future RCTs focusing on histology subset-specific treatment for SNM.
Left ventricular depression and pulmonary edema in rats after short-term normobaric hypoxia: effects of adrenergic blockade and reduced fluid load
Authors: Appelt Peter , Gabriel Philipp , Bölter Christian , Fiedler Nicole , Schierle Katrin , Salameh Aida , Rassler Beate 
Published: September 2021

AbstractAcute normobaric hypoxia may induce pulmonary injury with edema (PE) and inflammation. Hypoxia is accompanied by sympathetic activation. As both acute hypoxia and high plasma catecholamine levels may elicit PE, we had originally expected that adrenergic blockade may attenuate the severity of hypoxic pulmonary injury. In particular, we investigated whether administration of drugs with reduced fluid load would be beneficial with respect to both cardiocirculatory and pulmonary functions in acute hypoxia. Rats were exposed to normobaric hypoxia (10% O2) over 1.5 or 6 h and received 0.9% NaCl or adrenergic blockers either as infusion (1 ml/h, increased fluid load) or injection (0.5 ml, reduced fluid load). Control animals were kept in normoxia and received infusions or injections of 0.9% NaCl. After 6 h of hypoxia, LV inotropic function was maintained with NaCl injection but decreased significantly with NaCl infusion. Adrenergic blockade induced a similar LV depression when fluid load was low, but did not further deteriorate LV depression after 6 h of infusion. Reduced fluid load also attenuated pulmonary injury after 6 h of hypoxia. This might be due to an effective fluid drainage into the pleural space. Adrenergic blockade could not prevent PE. In general, increased fluid load and impaired LV inotropic function promote the development of PE in acute hypoxia. The main physiologic conclusion from this study is that fluid reduction under hypoxic conditions has a protective effect on cardiopulmonary function. Consequently, appropriate fluid management has particular importance to subjects in hypoxic conditions.
Caregiver burden by treatment and clinical characteristics of patients with glioblastoma
Authors: Au Trang H. , Willis Connor , Reblin Maija , Peters Katherine B. , Nghiemphu Phioanh Leia , Taylor Jennie W. , Colman Howard , Cohen Adam L. , Ormond D. Ryan , Chakravarti Arnab , Willmarth Nicole , Menon Jyothi , Ma Junjie , Bauer Hillevi , Watanabe Alexandre H. , Ulrich Cornelia M. , Singh Prianka , Marshall Alexander , Korytowsky Beata , Stenehjem David , Brixner Diana 
Published: September 2021

Abstract
Background
Glioblastoma is an incurable disease with a poor prognosis. For caregivers of people with glioblastoma, the burden of care can be high. Patients often present with different clinical characteristics, which may impact caregiver burden in different ways. This study aimed to evaluate associations between patient clinical characteristics and caregiver burden/quality of life (QoL).

Methods
Caregiver–patient dyads were enrolled at 7 academic cancer centers in the United States. Eligible caregiver participants were self-reported as the primary caregiver of an adult living with glioblastoma and completed a caregiver burden survey. Eligible patients were age ≥ 18 years at glioblastoma diagnosis and alive when their respective caregiver entered the study, with the presence of cognitive dysfunction confirmed by the caregiver. Data were analyzed with descriptive statistics and multivariable analyses.

Results
The final cohort included 167 dyads. Poor patient performance status resulted in patient difficulty with mental tasks, more caregiving tasks, and increased caregiving time. Language problems were reported in patients with left-sided lesions. Patient confusion was negatively associated with all caregiver domains: emotional health, social health, general health, ability to work, confidence in finances, and overall QoL. Better caregiver QoL was observed in patients with frontal lobe lesions versus non-frontal lobe lesions.

Conclusion
This study reinforced that patient performance status is a critical clinical factor that significantly affects caregiver burden, caregiving tasks, and caregiver time. Additionally, patient confusion affects multiple facets of caregiver burden/QoL. These results could be used to support guided intervention for caregiver support, customized to the patient experience.