bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mild repetitive head impacts alter perivascular flow in the midbrain dopaminergic system in awake rats
Authors: Cai Xuezhu , Harding Ian C , Sadaka Aymen H , Colarusso Bradley , Kulkarni Praveen , Ebong Eno , Qiao Ju , O'Hare Nick R , Ferris Craig F 
Published: October 2021

Abstract
Head injury is a known risk factor for Parkinson’s disease. Disruption in the perivascular clearance of metabolic waste and unwanted proteins is thought to be a contributing factor to disease progression. We hypothesized that repetitive mild head impacts, without evidence of structural brain damage, would increase microgliosis and AQP4 expression and depolarization and alter perivascular flow in the midbrain dopaminergic system. Adult male rats were subjected to sham, or two mild head impacts separated by 48 h. Three weeks later, fully awake rats were imaged using dynamic, contrast-enhanced MRI to follow the distribution of intraventricular gadobenate dimeglumine contrast agent. Images were registered to and analysed using a 3D MRI rat atlas providing site-specific data on 171 different brain areas. Following imaging, rats were tested for cognitive function using the Barnes maze assay. Histological analyses of tyrosine hydroxylase, microglia activation and AQP4 expression and polarization were performed on a parallel cohort of head impacted rats at 20 days post insult to coordinate with the time of imaging. There was no change in the global flux of contrast agent between sham and head impacted rats. The midbrain dopaminergic system showed a significant decrease in the influx of contrast agent as compared to sham controls together with a significant increase in microgliosis, AQP4 expression and depolarization. There were no deficits in cognitive function. The histology showed a significant level of neuroinflammation in the midbrain dopaminergic system 3 weeks post mild repetitive head impact but no loss in tyrosine hydroxylase. MRI revealed no structural brain damage emphasizing the potential serious consequences of mild head impacts on sustained brain neuroinflammation in this area critical to the pathophysiology of Parkinson’s.
Combined neurogenic pulmonary oedema and atypical Takotsubo cardiomyopathy in a patient with ischaemic stroke: a unique case report
Authors: Riva Letizia , Casella Gianni , Simonetti Luigi , Zini Andrea 
Published: October 2021

Abstract

Background
Neurogenic pulmonary oedema (NPO) and Takotsubo cardiomyopathy are rare complications of ischaemic stroke. They are considered to be due to an excess catecholamine release after sympathetic nervous stimulation following stroke onset. Among the different types of Takotsubo cardiomyopathy, apical ballooning is recognized as the typical form, but three atypical patterns have been described (midventricular, basal, and focal) which are more commonly observed in patients with neurological disorders.

Case summary
A 78-year-old woman was treated with intravenous alteplase and underwent mechanical thrombectomy for ischaemic stroke. During the procedure, her respiratory condition quickly worsened requiring invasive mechanical ventilation because of a wide and persistent reduction of the inspiratory oxygen fraction/arterial partial oxygen pressure ratio. Transthoracic echocardiography revealed moderate left ventricular systolic dysfunction with akinesis of the septal-apical and inferior-apical segments. Coronary angiography excluded obstructive lesions and/or evidence of acute plaque rupture. Ventriculography confirmed akinesis/dyskinesis of the inferior segment of the left ventricular apex associated with normal kinesis of the remaining segments. Chest X-ray revealed an infiltrative shadow on both lungs. After 24 h from NPO onset, her respiratory function improved and she was finally discharged on Day 7 without neurological defects. Left ventricular systolic dysfunction was reversible and ejection fraction normalized in 3 months.

Discussion
It is a very rare case of simultaneous NPO and Takotsubo cardiomyopathy following ischaemic stroke. Moreover, it is unique in that it is the first observation of NPO associated with an atypical pattern of Takotsubo cardiomyopathy, which is more frequent in patients with neurological disorders. A rapid recognition and treatment are essential for patient survival.
A case report of deglutition triggered atrial fibrillation in a patient with Laing distal myopathy
Authors: Alvarez Chikezie K , Swales Heather , Kluger Jeffrey 
Published: October 2021

AbstractBackgroundDeglutition-induced atrial fibrillation is a rare clinical entity with a reported prevalence of 0.6%. Laing distal myopathy is a rare autosomal dominant muscular dystrophy that is the result of mutations within the slow skeletal muscle fibre myosin heavy chain gene (MYH7). Atrial fibrillation has not been previously reported in patients with Laing distal myopathy. We describe the first reported case of deglutition triggered atrial fibrillation in a female with a history of Laing distal myopathy.Case summaryA 44-year-old female with a history of Laing distal myopathy diagnosed at age 32, began experiencing intermittent episodes of pre-syncope and palpitations which occurred after deglutition with food. An ambulatory 30-day patient triggered event monitor recorded episodes of atrial fibrillation with rapid ventricular response. Family history was significant for Laing distal myopathy, atrial fibrillation, as well as sudden cardiac death. Laboratory data, transthoracic echocardiogram, cardiac magnetic resonance imaging, and an exercise treadmill SPECT Imaging stress test were normal. An oesophagram revealed a mild oesophageal dysmotility with no other abnormalities. She was started on flecainide 50 mg p.o. every 8 h and verapamil 40 mg p.o. every 8 h with no further episodes of atrial fibrillation.DiscussionGiven the strong genetic component of this myopathy, one could postulate as to a possible genetic component in the development of atrial fibrillation in our patient. Although we cannot make definite correlation between deglutition-induced atrial fibrillation and Laing myopathy, it is important to report this unusual association which has not been described before.
Enhanced 3D visualization for planning biventricular repair of double outlet right ventricle: a pilot study on the advantages of virtual reality
Authors: Milano Elena Giulia , Kostolny Martin , Pajaziti Endrit , Marek Jan , Regan William , Caputo Massimo , Luciani Giovanni Battista , Mortensen Kristian H , Cook Andrew C , Schievano Silvia , Capelli Claudio 
Published: October 2021

Abstract

Aims
We aim to determine any additional benefit of virtual reality (VR) experience if compared to conventional cross-sectional imaging and standard three-dimensional (3D) modelling when deciding on surgical strategy in patients with complex double outlet right ventricle (DORV).

Methods and results
We retrospectively selected 10 consecutive patients with DORV and complex interventricular communications, who underwent biventricular repair. An arterial switch operation (ASO) was part of the repair in three of those. Computed tomography (CT) or cardiac magnetic resonance imaging images were used to reconstruct patient-specific 3D anatomies, which were then presented using different visualization modalities: 3D pdf, 3D printed models, and VR models. Two experienced paediatric cardiac surgeons, blinded to repair performed, reviewed each case evaluating the suitability of repair following assessment of each visualization modalities. In addition, they had to identify those who had ASO as part of the procedure. Answers of the two surgeons were compared to the actual operations performed. There was no mortality during the follow-up (mean = 2.5 years). Two patients required reoperations. After review of CT/cardiac magnetic resonance images, the evaluators identified the surgical strategy in accordance with the actual surgical plan in 75% of the cases. When using 3D pdf this reached only 70%. Accordance improved to 85% after revision of 3D printed models and to 95% after VR. Use of 3D printed models and VR facilitated the identification of patients who required ASO.

Conclusion
Virtual reality can enhance understanding of suitability for biventricular repair in patients with complex DORV if compared to cross-sectional images and other 3D modelling techniques.
The age-specific prognostic impact of the platelet-to-lymphocyte ratio on long-term outcome after acute coronary syndrome
Authors: Kazem Niema , Hofer Felix , Koller Lorenz , Hammer Andreas , Hofbauer Thomas M , Hengstenberg Christian , Niessner Alexander , Sulzgruber Patrick 
Published: October 2021

AbstractAimsPersonalized risk stratification within the ageing society after acute coronary syndrome (ACS) remains scarce but in urgent need. Increased platelet activity together with inflammatory activation play a key role during ACS. We aimed to evaluate the age-specific prognostic potential of the platelet to lymphocyte ratio (PLR) on long-term cardiovascular mortality after ACS.Methods and resultsPatients presenting with ACS admitted to the Vienna General Hospital between December 1996 and January 2010 were enrolled within a clinical registry including assessment of peripheral blood samples. The impact of the PLR on survival was assessed by Cox-regression hazard analysis. We included a total of 681 patients with a median age of 64 years (interquartile range: 45–84). Two hundred (29.4%) individuals died during the median follow-up time of 8.5 years. A strong and independent association of the PLR with cardiovascular mortality was found in the total study population [adjusted (adj.) hazard ratio (HR) per 1 standard deviation (1 SD) of 1.07 (95% confidence interval, CI: 1.03–1.10); P &lt; 0.001]. After stratification in individuals &lt;65 years (n = 339) and ≥65 years (n = 342), a prognostic effect of the PLR on cardiovascular mortality was solely observed in elderly patients ≥65 years [adj. HR per 1 SD of 1.04 (95% CI: 1.00–1.08); P = 0.039], but not in their younger counterparts &lt;65 years [adj. HR per 1 SD of 0.97 (95% CI: 0.83–1.14); P = 0.901].ConclusionThe present investigation highlights a strong and independent age-specific association of the PLR with cardiovascular mortality in patients with ACS. The PLR only allows to identify patients ≥65 years at high risk for fatal events after ACS—even from a long-term perspective.
Duration of toothbrushing with fixed appliances: a randomized crossover clinical trial
Authors: Koretsi Vasiliki , Klinke Rebecca , Herreiner Philip , Proff Peter , Kirschneck Christian 
Published: October 2021

Summary

Objective
Fixed orthodontic appliances might result in dental adverse effects, if sufficient oral hygiene is not maintained. Since recommendations on toothbrushing times are lacking scientific justification in orthodontic populations, the aim of the present study was to comparatively quantify the duration of toothbrushing with a manual and a powered toothbrush in two distinct age groups.

Trial design
Two-centre, two-period crossover balanced randomized clinical trial with computer-generated numbers and blinding at the outcome-assessing level.

Methods
Children and adults with fixed appliances with at least 22 aligned teeth were recruited at a university clinic and private practice in Bavaria, Germany. Plaque was disclosed with staining tablets and participants brushed their teeth with their habitual technique in front of a mirror and without interference until staining was, to their own satisfaction, completely removed. The primary outcome was duration of toothbrushing in seconds. Secondary outcomes were percentage plaque reduction and questionnaire data on dental attitudes and behaviours. Data were analysed with linear mixed models.

Results
Twenty-eight participants were randomized to the first and 27 to the second toothbrush sequence. The combined effect of age and toothbrush on the duration of toothbrushing was evident (n = 52, F(1, 50.8) = 5.1, P = 0.028). Children brushed 14.5 seconds less [n = 28, 95% confidence interval (CI) = −31.3 to 2.3, P = 0.090], yet adults 13.3 seconds more (n = 24, 95% CI = −4.6 to 31.3, P = 0.143) with the manual than powered toothbrush. Brushing times ranged from 2 minutes and 45 seconds to 3 minutes and 17 seconds with plaque reduction at 76% and good dental attitudes and behaviours.

Conclusions
Both children and adults with fixed appliances might equally reach an effective plaque reduction with either manual or powered toothbrushes and their habitual brushing technique in around three minutes, if plaque is visible.

Registration
DRKS—German Clinical Trials Register ID: DRKS00012463.

Funding
Oral-B Procter & Gamble.
‘Gott Strafe England’: Ivor Gurney’s Strafes and Ways
Authors: Brooks Martin 
Published: October 2021

Abstract
This essay describes Ivor Gurney’s use of the word ‘strafe’ in his poems of the First World War. At the outbreak of the War, the word was a new arrival in the English national consciousness. It had come to prominence in the German Army’s slogan, ‘Gott strafe England’ (‘God punish England’). Allied counterpropagandists soon redeployed this slogan as evidence that the German people were hateful and frenzied, and it gained currency as an informal English noun for a German artillery bombardment. In poems dating from during and after the War, Gurney draws on ‘strafe’s’ interlinguistic existence to express his contempt for the two powers’ propaganda. In treating the word as fluctuating between two languages, Gurney stages his separation from both English and German narratives of nationhood. Tracking his use of the word ‘strafe’ shows how he described the importance of individual experiences for understanding the War, portrayed a sense of ‘Wonder’ that he suggested could define soldier poets, and expressed his post-war belief that England had betrayed him. By outlining how Gurney attached these possibilities to ‘strafe’, this essay contributes to the wider critical understanding of how and why he wrote about his War experiences.
Engaging with Public Opinion at the Micro-Level: Citizen Dialogue and Participation in German Foreign Policy
Authors: Opitz Christian , Pfeifer Hanna , Geis Anna 
Published: October 2021

AbstractThis article analyzes how and why foreign policy (FP)-makers use dialogue and participation processes (DPPs) with (groups of) individual citizens as a source of public opinion. Taking Germany as a case study and drawing on DPP initiatives by the Federal Foreign Office (Auswärtiges Amt, AA) since 2014, we analyze the officials’ motivation for establishing such processes and find four different sets of motivation: (1) image campaigning, (2) educating citizens, (3) listening to citizens, and (4) changing the citizens’ role in FP. Our article makes three contributions. First, we provide a novel typology of the sources of public opinion upon which FP-makers can draw. Second, our study points to the importance of, and provides a framework for, analyzing how officials engage with public opinion at the micro-level, which has so far been understudied in FP analysis. Finally, our empirical analysis suggests that both carefully assessing and influencing public opinion feature prominently in motivation, whereas PR purposes are of minor importance. Recasting the citizens’ role in FP gains in importance over time and may mirror the increased need to legitimize FP in Western democracies vis-à-vis their publics.
The Contribution of Plasma Urea to Total Osmolality During Iatrogenic Fluid Reduction in Critically Ill Patients
Authors: Nihlén Sandra , Frithiof Robert , Titze Jens , Kawati Rafael , Rasmusson Johan , Rylander Christian , Pikwer Andreas , Castegren Markus , Belin Anton , Hultström Michael , Lipcsey Miklos 
Published: October 2021

Abstract
Hyperosmolality is common in critically ill patients during body fluid volume reduction. It is unknown whether this is only a result of decreased total body water or an active osmole-producing mechanism similar to that found in aestivating animals, where muscle degradation increases urea levels to preserve water. We hypothesized that fluid volume reduction in critically ill patients contributes to a shift from ionic to organic osmolytes similar to mechanisms of aestivation. We performed a post-hoc analysis on data from a multicenter observational study in adult intensive care unit (ICU) patients in the postresuscitative phase. Fluid, electrolyte, energy and nitrogen intake, fluid loss, estimated glomerular filtration rate (eGFR), and estimated plasma osmolality (eOSM) were registered. Contributions of osmolytes Na+, K+, urea, and glucose to eOSM expressed as proportions of eOSM were calculated. A total of 241 patients were included. eOSM increased (median change 7.4 mOsm/kg [IQR−1.9–18]) during the study. Sodium's and potassium's proportions of eOSM decreased (P &lt; .05 and P &lt; .01, respectively), whereas urea's proportion increased (P &lt; .001). The urea’s proportion of eOSM was higher in patients with negative vs. positive fluid balance. Urea's proportion of eOSM increased with eOSM (r = 0.63; adjusted for eGFR r = 0.80), but not nitrogen intake. In patients without furosemide and/or renal replacement therapy (n = 17), urea’s proportion of eOSM and eOSM correlated strongly (r = 0.92). Urea’s proportion of eOSM was higher in patients not surviving up to 90 d. In stabilized ICU patients, the contribution of urea to plasma osmolality increased during body water volume reduction, statistically independently of nitrogen administration and eGFR. The shift from ionic osmolytes to urea during body fluid volume reduction is similar to that seen in aestivating animals.
ClinicalTrials.org Identifier: NCT03972475.
A genetic toolkit for studying transposon control in the Drosophila melanogaster ovary
Authors: ElMaghraby Mostafa F , Tirian Laszlo , Senti Kirsten-André , Meixner Katharina , Brennecke Julius 
Published: October 2021

Abstract
Argonaute proteins of the PIWI clade complexed with PIWI-interacting RNAs (piRNAs) protect the animal germline genome by silencing transposable elements. One of the leading experimental systems for studying piRNA biology is the Drosophila melanogaster ovary. In addition to classical mutagenesis, transgenic RNA interference (RNAi), which enables tissue-specific silencing of gene expression, plays a central role in piRNA research. Here, we establish a versatile toolkit focused on piRNA biology that combines germline transgenic RNAi, GFP marker lines for key proteins of the piRNA pathway, and reporter transgenes to establish genetic hierarchies. We compare constitutive, pan-germline RNAi with an equally potent transgenic RNAi system that is activated only after germ cell cyst formation. Stage-specific RNAi allows us to investigate the role of genes essential for germline cell survival, for example, nuclear RNA export or the SUMOylation pathway, in piRNA-dependent and independent transposon silencing. Our work forms the basis for an expandable genetic toolkit provided by the Vienna Drosophila Resource Center.
Unraveling the Gordian knot: genetics and the troubled road to effective therapeutics for Alzheimer’s disease
Authors: Restifo Linda L 
Published: October 2021

AbstractIn the late 20th century, identification of the major protein components of amyloid plaques and neurofibrillary tangles provided a window into the molecular pathology of Alzheimer’s disease, ushering in an era of optimism that targeted therapeutics would soon follow. The amyloid-cascade hypothesis took hold very early, supported by discoveries that dominant mutations in APP, PSEN1, and PSEN2 cause the very rare, early-onset, familial forms of the disease. However, in the past decade, a stunning series of failed Phase-3 clinical trials, testing anti-amyloid antibodies or processing-enzyme inhibitors, prompts the question, What went wrong? The FDA’s recent controversial approval of aducanumab, despite widespread concerns about efficacy and safety, only amplifies the question. The assumption that common, late-onset Alzheimer’s is a milder form of familial disease was not adequately questioned. The differential timing of discoveries, including blood–brain–barrier-penetrant tracers for imaging of plaques and tangles, made it easy to focus on amyloid. Furthermore, the neuropathology community initially implemented Alzheimer’s diagnostic criteria based on plaques only. The discovery that MAPT mutations cause frontotemporal dementia with tauopathy made it even easier to overlook the tangles in Alzheimer’s. Many important findings were simply ignored. The accepted mouse models did not predict the human clinical trials data. Given this lack of pharmacological validity, input from geneticists in collaboration with neuroscientists is needed to establish criteria for valid models of Alzheimer’s disease. More generally, scientists using genetic model organisms as whole-animal bioassays can contribute to building the pathogenesis network map of Alzheimer’s disease.
Life-space Mobility in Older Men: The Role of Perceived Physical and Mental Fatigability
Authors: Moored Kyle D , Rosso Andrea L , Gmelin Theresa , Qiao Yujia (Susanna) , Carlson Michelle C , Cawthon Peggy M , Cauley Jane A , Glynn Nancy W 
Published: October 2021

Abstract

Background
Physical performance and fatigue can limit mobility within the larger environment (life-space mobility). It is unknown whether perceived fatigability, self-reported fatigue anchored to activity intensity and duration, is independently associated with life-space.

Methods
We assessed this cross-sectionally in Visit 4 (2014–2016) of the Osteoporotic Fractures in Men Study (MrOS; N = 1 672, Age: Mean = 84.2 ± 4.0 years). The Pittsburgh Fatigability Scale (PFS, range: 0–50; higher = greater fatigability) measured physical (Mean = 16.1 ± 9.4) and mental fatigability (Mean = 7.5 ± 7.9). Life Space Assessment scores incorporated level, frequency, and assistance used for life-space mobility (range: 0–120, higher = greater life-space mobility; life-space constriction: inability to leave neighborhood without assistance). Separate multiple linear and logistic regressions for physical and mental fatigability were sequentially adjusted for demographic, health/lifestyle, and performance measures.

Results
The mean life-space mobility score was 84.6 ± 21.8, and 18% (n = 296) of men had life-space constriction. Higher physical and mental fatigability were both associated with lower life-space mobility in models adjusted for health and lifestyle factors (Physical PFS: B = −2.37, 95% confidence interval [CI]: [−3.39, −1.35]; Mental PFS: B = −1.79, 95% CI: [−2.73, −0.84]). Men with higher fatigability also had increased risk of life-space constriction (Physical PFS: OR = 1.59, 95% CI: [1.32, 1.92]; Mental PFS: OR = 1.25, 95% CI: [1.08, 1.46]). Associations were larger in magnitude for physical versus mental fatigability. Adjusting for physical performance measures more strongly attenuated associations for physical compared to mental fatigability.

Conclusions
Fatigability is linked with real-world mobility in older men, independent of their physical health. This association may be driven by separate physical and cognitive mechanisms worth examining further in longitudinal studies.