bluuebunny/crossref_metadata_2025 huggingface dataset:
P.103 Imaging neuron-glioma cell interactions in freely behaving animals with a novel implantable mini-microscope
Authors: Keough M , Shamardani K , Monje M
Published: June 2023

Background: High grade gliomas (HGG) are diffusely infiltrative brain tumours with dismal prognosis. Recent studies from our lab have demonstrated that glioma cells form synapses with surrounding neurons, and proliferate in response to neuronal input. How these neuron-glioma networks develop, and are influenced by experience, is currently unknown. We aimed to develop a novel imaging tool to study neuron-glioma cell interactions in freely behaving animals. Methods: Several patient-derived HGG cell lines were transfected to express the green calcium indicator GCaMP6s. These cells were xenografted into the premotor cortex of mice, along with a virus expressing the red calcium indicator jRGECO1a under a neuron-specific synapsin promotor to allow dual-color imaging of neurons and glioma cells. The Inscopix mini-microscope system was implanted into the cortex to allow real-time live calcium imaging in freely behaving animals. Results: Several HGG cell lines effectively expressed the GCaMP6s calcium indicator. In vivo, we were successfully able to image both neurons and glioma cells simultaneously in freely behaving mice in real time. Conclusions: The Inscopix system has been modified for studying cancer cells for the first time. This technology will be used to study how pharmacological agents and neuronal experience shape neuron-glioma circuit dynamics, to develop new therapeutic strategies for HGG.
P.115 MRI based methodology for assessment of white matter neuroplasticity: preclinical validation using human motor training data
Authors: Grajauskas LA , Kirby ED , Frizzell TO , Song X , D’Arcy RC
Published: June 2023

Background: Disruption of white matter (WM) tracts is common in traumatic injury to the brain and spinal cord. However, imaging techniques for prognostication and monitoring of recovery are lacking. Myelin Water Imaging (MWI) is a validated MRI based method of quantifying myelin volume and represents a potential tool for application in a clinical environment. Methods: 12 healthy, right-handed participants completed a two-week visuomotor maze training program with MRI scans at baseline and endpoint. The task was designed to be difficult for the non-dominant hand and easy for the dominant, allowing for an inbuilt control. Diffusion Tensor Imaging (DTI) along with MWI data were collected at both timepoints using a 3T MRI. Results: Performance metrics confirmed task performance increased only in the non-dominant hand, and a corresponding endpoint>baseline comparison showed significant increases in the MWF (p<0.05) and DTI indices (p<0.05) in the right corticospinal tract (CST), and no significant change in the left CST. Conclusions: This preclinical validation shows MWI is capable of quantitatively tracking WM changes over the course of weeks in humans. MWI’s clinical utility lies in its ability to assess WM changes over short time periods, as monitoring changes in tissue integrity will assist in guiding treatment decisions after critical injury.
P.118 Near infrared spectroscopy based indices of cerebrovascular reactivity cluster with intracranial pressure based indices in moderate to severe TBI patients
Authors: Gomez A , Sainbhi AS , Froese L , Vakitbilir N , Stein K , Zeiler FA
Published: June 2023

Background: Cerebrovascular reactivity has been identified as an important contributor to secondary injury following moderate to severe traumatic brain injury (TBI). “Gold-standard” intracranial pressure (ICP) based indies of cerebrovascular reactivity are limited by their invasive nature poor spatial resolution. Near infrared spectroscopy (NIRS) based indices of cerebrovascular reactivity are minimally invasive and have improved spatial resolution. In this study, classical machine-learning algorithms are leveraged to better characterize the relationship between these indices. Methods: High-resolution physiologic data was collected in a cohort of adult moderate to severe TBI patients. From this data both ICP and NIRS based indices of cerebrovascular reactivity were derived. Utilizing Agglomerative Hierarchical Clustering (AHC) and Principal Component Analysis, the relationship between these indices in higher dimensional physiologic space was examined. Results: A total of 83 patients with 314,395 minutes of unique and complete physiologic data was obtained. Through AHC and PCA there was higher order clustering between NIRS and ICP based indices, separate from other physiologic parameters. Conclusions: NIRS and ICP based indices of cerebrovascular reactivity relate to one another in higher dimensional physiologic space. NIRS based indices of cerebrovascular reactivity may be a viable alternative to ICP based indices.
P.123 Metabolic acidosis and functional outcome after aneurysmal subarachnoid hemorrhage: an exploratory analysis
Authors: Veilleux C , Eagles ME , Tso MK , Macdonald RL
Published: June 2023

Background: Little data exists on the impact of metabolic acidosis in aneurysmal subarachnoid hemorrhage (aSAH). Given its detrimental effects in critically ill patients, we inquired whether in patients with aSAH, metabolic acidosis (bicarbonate <22mmol/L) was associated with an increased risk of worse outcomes at 3 months (mRS >2). Methods: We performed a retrospective analysis of the CONSCIOUS-1 randomized control trial dataset including all patients who had at least three bicarbonate levels drawn. Bivariate and multivariate logistic regression models were used to assess for independent relationship between metabolic acidosis and functional outcome at 3 months. Delayed cerebral ischemia (DCI) was assessed for potential effect modification. Results: Three hundred and nineteen patients were included in our analysis. There was no difference in the proportion of poor outcome between those with or without metabolic acidosis on bivariate analysis (OR=1.022, p=0.949). However, amongst individuals who develop DCI, there was increased odds of unfavorable outcome when patients developed metabolic acidosis (OR=7.588, p=0.023). Conclusions: Individuals who develop delayed cerebral ischemia may benefit from having their bicarbonate level carefully monitored. More studies are needed to determine how the development of metabolic acidosis can be mitigated, and whether its prevention leads to improved outcomes.
P.124 Delayed cerebral ischemia and cognitive outcomes after aneurysmal subarachnoid hemorrhage: an exploratory analysis
Authors: Veilleux C , Eagles ME , Macdonald RL
Published: June 2023

Background: Neuropsychological outcomes are an important component of the morbidity after aneurysmal subarachnoid hemorrhage (aSAH). Data on the relationship between delayed cereberal ischemia (DCI) and neuropsychological outcomes remains sparse. We herein assess the relationship between DCI and neuropsychological outcomes, as measured by the Montreal Cognitive Assessment score (MoCA) at 90 days in patients with aSAH. Methods: We performed a post-hoc analysis of the Nimodipine Microparticles to Enhance Recovery While Reducing Toxicity After Subarachnoid Hemorrhage (NEWTON-2) clinical trial. Patients were grouped based on whether they developed delayed cerebral ischemia. We assessed the relationship between MoCA scores and DCI with Student’s t-test and regression modeling. Age, sex, history of hypertension, and WFNS grade were included as covariates in the model. Results: Two-hundred and fifteen patients were included in our analysis. Mean MoCA score at 90 days in our population was 22. Mean MoCA scores were significantly lower in patients who developed DCI compared to those who did not (23.7 vs 18.4, p<0.001). Age, WFNS grade, and development of DCI were independently associated with MoCA scores in the regression model (p < 0.05). Conclusions: DCI is a predictor of decreased neuropsychological outcomes in aSAH survivors and may contribute to the morbidity burden in this population.
P.128 Recurrent subarachnoid hemorrhage secondary to Chiari 1 malformation
Authors: Tso MK , Omahen D
Published: June 2023

Background: We describe a patient with recurrent subarachnoid hemorrhage (SAH) secondary to Chiari 1 malformation. Methods: A retrospective review of the clinical chart was performed. Results: A previously healthy female in her 70’s presented with worst headache of life. CT demonstrated 4th ventricular hemorrhage with SAH extending into the bilateral cerebellomedullary fissures. CTA did not show a vascular etiology and patient was discharged home. Incidental note was made of a right persistent trigeminal artery. The patient then represented 2 weeks later with worst headache of life and decreased level of consciousness. CT demonstrated extensive SAH extending into the 3rd and 4th ventricles. CTA and diagnostic cerebral angiogram did not show a vascular etiology. MRI brain/C-spine revealed Chiari 1 malformation. An external ventricular drain was placed but could not be weaned. She underwent suboccipital craniectomy with C1 laminectomy. Intraoperatively, there was a prominent dorsal spinal vein that appeared under tension as it pierced the arachnoid membrane and subsequently entering the dura as a rudimentary occipital sinus. This vein was coagulated and divided. The patient recovered well and was at neurological baseline at 6 month follow-up. Conclusions: This is the first reported case of recurrent SAH secondary to Chiari 1 malformation.
P.129 Endovascular coiling of ruptured basilar fenestration aneurysm: case report and review of literature
Authors: Liu E , Toyota P , Newton B , Pendleton N , Marciniuk K , Persad A , Peeling L , Kelly M
Published: June 2023

Background: Basilar fenestration is a rare congenital anomaly. When present, it is commonly found at the proximal portion of the artery near the vertebrobasilar junction. Methods: This is a case report of a ruptured basilar fenestration aneurysm in a 47-year-male successfully treated with endovascular coiling. Results: A 47-year-old male presented with sudden onset headache, neck pain, blurry vision, nausea, vomiting, and diaphoresis. Cerebral angiogram revealed a saccular basilar fenestration aneurysm located at the vertebrobasilar junction measuring 3.1 x 2.6 x 3.4 mm with a 2.3 mm neck. Multiple coils were placed including Target 360 Nano 2mm x 4 cm (Stryker, Kalamazoo, MI, US), Target 360 Nano 1.5 mm x 2 cm (Stryker, Kalamazoo, MI, US), and Target Helical Nano 1.5 mm x 1 cm (Stryker, Kalamazoo, MI, US). A repeat angiogram revealed complete exclusion of the aneurysm with preservation of both vertebral arteries. Conclusions: A literature review was conducted on basilar fenestration aneurysms which included 158 patients from 39 studies. Overall, complete exclusion of the aneurysm was achieved in 75.8% of cases, with 22.4% of cases having residual flow and 1.8% of cases with unreported exclusion status.
P.135 Dura splitting technique for surgical resection of spinal meningioma
Authors: Elashaal AA , Elashaal Y
Published: June 2023

Background: Spinal meningiomas are intradural extramedullary tumors that account for 25–46% of all primary spinal tumors. A growing body of literature suggests that the extent of resection significantly affects the recurrence rate of spinal meningiomas and that Simpson grade II resection may not be as adequate as previously thought. Dura Splitting Technique (DST) can be used with no major perioperative complications. Methods: Retrospect review of six cases of spinal meningiomas where DST was used. The patients ranged in age at presentation from 38 to 80 years. All presented with symptoms including gait unsteadiness and lower limbs weakness. Spinal MRI was used to establish the diagnosis. All of the tumors were located ventral or ventrolateral to the spinal cord. Results: DST was applying to spinal meningioma cases,complete tumor resection by separating the involved dura into inner and outer layer. Preserving the dura outer layer and avoiding the need for dural graft reconstruction and CSF leak. A total of six cases, four in thoracic spine and two in cercical spine one anterior and one posterior, all four cases had no reported surgical complications or tumor recurrenc. Conclusions: We confirm that DST is safe and a superior method in the treatment of spinal meningiomas.
P.142 Characteristics of a large cohort of patients with acromegaly with surgical outcome by geographic living location
Authors: Mann JA , Lithgow K , Starreveld Y , Riva-Cambrin J
Published: June 2023

Background: Acromegaly is a rare disease caused by a growth hormone-secreting pituitary adenoma which results in potentially debilitating skeletal, cardiac and gastrointestinal disease. Surgical resection can be curative, but in Southern Alberta, skull base surgeons and multi-disciplinary pituitary teams work at a single centre, raising the question of whether rurally-dwelling patients experience worse outcomes. We aim to characterize post-surgical remission rates by living location in acromegaly patients at our institution. Methods: A retrospective chart review supplemented a single surgeon database of patients with acromegaly treated at our centre (February 2011-April 2022) with demographic, endocrinological, and surgical variables. Statistical analysis was performed using Stata Version 17. Results: Our cohort included 47 cases of acromegaly (53% male), all treated with endoscopic transsphenoidal surgery. The average age at first operation was 46.7 years (20-69 years), 77% were macroadenomas, and the average adenoma size at initial MRI was 16mm. 54.55% of the urban cohort achieved immediate post-surgical remission, versus 28.57% of the rural cohort (OR:3.0(95%CI:0.67,15.51)). Conclusions: The characteristics of our cohort agree with the literature. The odds of immediate post-surgical remission in urban-dwelling patients was 3.0 times that of rurally-dwelling patients. Our results failed to meet statistical significance likely due to lack of power secondary to sample size.
A.5 Neurovascular complications of veno-venous extracorporeal membrane oxygenation in critically ill COVID-19 patients
Authors: Li C , Ma Y , Deng D , Li C , Dawson E , Wang D , Gofton T , Nagpal AD , Slessarev M
Published: June 2023

Background: Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is an invasive intervention for patients with respiratory failure associated with COVID-19. This meta-analysis aims to determine the incidence of neurovascular complications in COVID-19 patients requiring VV-ECMO. Methods: Systematic literature search of MEDLINE, Embase, PsycINFO, and Cochrane databases was performed to identify studies that reported neurovascular complications of adult COVID-19 patients on VV-ECMO for respiratory failure. Case series and reports were excluded. Studies with 95% or more of its patients on VV-ECMO were pooled for meta-analysis. Results: Eighteen studies (n=1968) were included for meta-analyses. In COVID-19 patients requiring VV-ECMO, the incidences of intracranial hemorrhage and ischemic stroke were 11% [95% CI, 8–15%] and 2% [95% CI, 1–3%], respectively. Intraparenchymal and subarachnoid hemorrhages accounted for 73% and 8% of all intracranial hemorrhages, respectively. The risk ratio of mortality in COVID-19 patients with neurovascular complications on VV-ECMO compared to patients without neurovascular complications was 2.24 [95% CI, 1.46–3.46]. Conclusions: COVID-19 patients requiring VV-ECMO have a higher incidence of intracranial hemorrhage compared to historical data in non-COVID-19 patients (11% vs. 8%), while the incidence of ischemic stroke is similar (2%) in both cohorts. COVID-19 patients with neurovascular complications on VV-ECMO are at an increased risk of death.
B.1 Imaging metabolic changes in white matter following ischemic and hemorrhagic stroke onset in an animal model
Authors: Pushie MJ , Boseley RE , Sylvain NJ , Peeling L , Kelly ME
Published: June 2023

Background: What matter (WM) is particularly sensitive to ischemia and WM changes are observed following onset of ischemic stroke as well as during expansion of the stroke lesion. To better correlate neurobehavioural and functional assessments in our models we have developed imaging methods to aid in the differentiation and quantification of WM injury. Methods: We employ 3 mouse models of stroke: photothrombotic, temporary middle cerebral artery occlusion, and intracerebral hemorrhage. Naïve controls and surgical shams (for each model) are also characterized. We use Fourier transform infrared (FTIR) imaging and synchrotron-based X-ray fluorescence microscopy (XFM) to visualize metabolites and elemental markers, respectively. These post-mortem imaging techniques are combined with conventional histology to confirm neuroanatomic features and cell types. Results: The metabolic profile of WM in naïve, sham, and stroke models has been characterized in C57BL/6 mice. The metabolic markers we identify are highly specific and enable the automated differentiation of WM from other tissues. Our methods have been re-tooled to identify degeneration and injury of WM regions. Conclusions: The combination of FTIR imaging and XFM afford the means to readily differentiate WM changes following stroke onset. Significant dysregulation can be observed before the core or penumbra of the stroke lesion reaches WM-containing regions.
B.4 Quantitative electroencephalography to predict post-stroke disability: a systematic review and meta-analysis
Authors: Sood I , Injety R , Farheen A , Kamali S , Jacob A , Mathewson K , Buck B , Kate M
Published: June 2023

Background: We aim to assess the role of quantitative electroencephalography (QEEG) derived indices to predict post-stroke disability. Methods: We included observational studies (sample-size≥10) of patients with stroke who underwent EEG and a follow-up outcome assessment was available either in form of a modified Rankin scale (mRS) or National Institute of stroke scale (NIHSS) or Fugl-Meyer scale (FMA). QEEG indices analyzed were delta-alpha ratio (DAR), delta-theta-alpha-beta ratio (DTABR), brain symmetry (BSI) and pairwise derived brain symmetry (pdBSI). Results: Twelve studies (11 had only ischemic stroke, and one had both ischemic and hemorrhagic stroke), including 513 participants were included for meta-analysis. Higher DAR was associated with worse mRS (n=300, Pearson’s r 0.26, 95% CI 0.21-0.31). Higher DTABR was associated with worse mRS (n=337, r 0.32, 95% CI 0.26-0.39). Higher DAR was associated with higher NIHSS (n=161, r 0.42, 95% CI0.24-0.6). Higher DTABR was associated with higher NIHSS (n=172, r 0.49, 95% CI 0.31-0.67). pdBSI was inversely associated with FMA (n=20, r-0.50 95% CI -0.86-(-0.14)) and BSI was not associated with FMA (n=21, r -0.3 95% CI -0.81-0.22). Conclusions: QEEG-derived indices have the potential to assess post-stroke disability. Adding QEEG to the clinical and imaging biomarkers may help in better prediction of post-stroke recovery.

PROSPERO 2022 CRD42022292281
Call for Faith: Religiousness, Religious Coping and Psychological Disturbance of Chinese Christians During COVID-19
Authors: Xie Zhongyao , Ren Zhengjia
Published: June 2023

Objectives:

This study is aimed at investigating the relationships between religious practice, religious coping strategies, and mental health among Chinese Christians in the context of the COVID-19 outbreak.

Methods:

A total of 915 participants from several cities in China completed online questionnaires, including sociodemographic data, mental disorder history, and years as a Christian, as well as frequency of weekly religious practice, Religious Coping Scale, the Patient Health Questionnaire-9 (PHQ-9), and the Generalized Anxiety Disorder scale (GAD-7).

Results:

The result of multivariate analysis indicated that during the COVID-19 pandemic, among Chinese Christians without a history of mental disorder, negative religious coping were associated with depression, and anxiety symptoms. Among Chinese Christians with a history of mental disorders, comorbidity with 1 mental disorder, comorbidity with 2 or more mental disorders, negative religious coping, and positive religious coping were associated with depression symptoms. Comorbidity with 2 or more mental disorders, negative religious coping, and positive religious coping were associated with anxiety symptoms.

Conclusion:

Christians with a previous history of mental illness are more likely to experience anxiety during the epidemic. In the future, mental health services during disasters may put more attention on certain religious groups and provide more spiritual care to maintain their well-being accordingly.
Unspecific Evidence and Normative Theories of Decision
Authors: Borchert Rhys
Published: June 2023

The nature of evidence is a problem for epistemology, but I argue that this problem intersects with normative decision theory in a way that I think is underappreciated. Among some decision theorists, there is a presumption that one can always ignore the nature of evidence while theorizing about principles of rational choice. In slogan form: decision theory only cares about the credences agents actually have, not the credences they should have. I argue against this presumption. In particular, I argue that if evidence can be unspecific, then an alleged counterexample to causal decision theory fails. This implies that what theory of decision we think is true may depend on our opinions regarding the nature of evidence. Even when we are theorizing about subjective theories of rationality, we cannot set aside questions about the objective nature of evidence.
A bronchoscopy-associated pseudo-outbreak of Mycobacterium chelonae and Mycobacterium mucogenicum associated with contaminated ice machine water and ice
Authors: Engers Drew W. , Swarup Rajeev , Morrin Cheryl , Blauw Mica , Selfridge Miles , Gonyon Pierre , Stout Janet E. , Malani Anurag N.
Published: June 2023

A pseudo-outbreak of bronchoscopy-associated Mycobacterium chelonae and M. mucogenicum was traced to contaminated ice machine water and ice. A nonsterile ice bath was used to cool uncapped, sterile, saline syringes used to slow procedural bleeding. Joining the growing evidence of bronchoscopy pseudo-outbreaks, our investigation describes several lessons for future prevention.
Forum: The Death of Queen Elizabeth II: Meaning and Media
Authors: Gullace Nicoletta F. , Chernock Arianne , Natarajan Radhika , Beers Laura
Published: June 2023

This is the revised transcript of a roundtable on the death of Queen Elizabeth II, presented at the North American Conference on British Studies in Chicago in November 2022. It includes an account of the many meanings of Queen Elizabeth II for her subjects and discussion of why so many at home and in the Commonwealth were devoted to her. The panel also touches on the significance for the monarchy of Elizabeth's passing, the meaning of queenship, and the importance of Elizabeth's gender for British women. An account of the queen and the Commonwealth focuses particularly on imperial optics and the queen's desire to be seen as the ruler of the Commonwealth. The panel concludes with the personalized account of a transnational scholar regarding the degree to which the media manufactured the appearance of grief over the queen's passing.
Lagrangian model for passive scalar gradients in turbulence
Authors: Zhang Xiaolong , Carbone Maurizio , Bragg Andrew D.
Published: June 2023

The equation for the fluid velocity gradient along a Lagrangian trajectory immediately follows from the Navier–Stokes equation. However, such an equation involves two terms that cannot be determined from the velocity gradient along the chosen Lagrangian path: the pressure Hessian and the viscous Laplacian. A recent model handles these unclosed terms using a multi-level version of the recent deformation of Gaussian fields (RDGF) closure (Johnson & Meneveau, Phys. Rev. Fluids, vol. 2 (7), 2017, 072601). This model is in remarkable agreement with direct numerical simulations (DNS) data and works for arbitrary Taylor Reynolds numbers

$\textit {Re}_\lambda$

. Inspired by this, we develop a Lagrangian model for passive scalar gradients in isotropic turbulence. The equation for passive scalar gradients also involves an unclosed term in the Lagrangian frame, namely the scalar gradient diffusion term, which we model using the RDGF approach. However, comparisons of the statistics obtained from this model with DNS data reveal substantial errors due to erroneously large fluctuations generated by the model. We address this defect by incorporating into the closure approximation information regarding the scalar gradient production along the local trajectory history of the particle. This modified model makes predictions for the scalar gradients, their production rates, and alignments with the strain-rate eigenvectors that are in very good agreement with DNS data. However, while the model yields valid predictions up to

$\textit {Re}_\lambda \approx 500$

, beyond this, the model breaks down.
Powder X-ray diffraction intensities of corundum calculated by conventional and density functional theory methods and extracted by deconvolutional treatment on experimental data
Authors: Ida Takashi
Published: June 2023

Least-squares analysis on the diffraction intensity values certified for NIST SRM676a and SRM1976c α-Al2O3 (corundum) have shown that the intensities of SRM1976c can be simulated by the March-Dollase preferred orientation model along the (001)-direction. Diffraction intensities of randomly oriented corundum crystallites have been calculated from electron density data obtained by conventional and density functional theory (DFT) calculations, on the assumption of independent and similar atomic displacements for Al and O atoms. The results of DFT calculations support that the strongest peak of randomly oriented α-Al2O3 crystalline powder should be 113-reflection, though the intensities simulated by DFT calculations are not closer to NIST SRM676a intensities than those expected for a fully ionized model ${\rm Al}_2^{3 + } {\rm O}_3^{2-}$. Diffraction data of two types of relatively fine (nominally 2–3 μm and ca 0.3 μm) α-Al2O3 powder have been collected and processed by a deconvolutional treatment (DCT). Integrated peak intensities extracted from the DCT data by an individual peak profile fitting method also support that the 113-reflection is the strongest reflection of randomly oriented α-Al2O3 crystalline powder.
Dimensions of internalizing symptoms are stable across early adolescence and predicted by executive functions: Longitudinal findings from the Adolescent Brain and Cognitive Development (ABCD) study
Authors: Vedechkina Maria , Bennett Marc , Holmes Joni
Published: June 2023

Early adolescence is characterized by rapid changes in executive function and increased vulnerability to internalizing difficulties. The aim of this study was to explore whether internalizing symptoms are stable across early adolescence and to identify possible links with executive function. Using data from the Adolescent Brain and Cognitive Development Study (ABCD), we identified four dimensions of internalizing symptoms from item-level ratings on the Child Behavior Checklist at ages 10 (n = 10,841) and 12 (n = 5,846), with an invariant factor structure across time. These dimensions corresponded to anxiety, depression, withdrawal, and somatic problems. We then examined associations between these dimensions and three aspects of executive function at age 10 measured by the NIH Toolbox: inhibition, shifting and working memory. Worse shifting and inhibition at age 10 was associated with elevated symptoms of anxiety and withdrawal cross-sectionally, while poor inhibition was also uniquely associated with symptoms of depression. Longitudinal associations were more limited: Worse inhibition at age 10 predicted greater symptoms of withdrawal at age 12, while worse shifting predicted fewer symptoms of anxiety 2 years later. These findings suggest that poor executive function in early adolescence is associated with greater internalizing difficulties and poor inhibition may contribute to later social withdrawal.
Long-Term Mortality in Patients Transferred by Emergency Medical Services: Prospective Cohort Study
Authors: Enriquez de Salamanca Gambara Rodrigo , Sanz-García Ancor , Martín-Conty José L. , Polonio-López Begoña , del Pozo Vegas Carlos , Martín-Rodríguez Francisco , López-Izquierdo Raúl
Published: June 2023

Objective:

This study aimed to determine the long-term mortality (one-year follow-up) associated with patients transferred by Emergency Medical Services (EMS), and to reveal the determinants (causes and risk factors).

Methods:

This was a multicenter, prospective, observational, controlled, ambulance-based study of adult patients transferred by ambulance to emergency departments (EDs) from October 2019 through July 2021 for any cause. A total of six Advanced Life Support (ALS) units, 38 Basic Life Support (BLS) units, and five hospitals from Spain were included. Physiological, biochemical, demographic, and reasons for transfer variables were collected. A longitudinal analysis was performed to determine the factors associated to long-term mortality (any cause).

Results:

The final cohort included 1,406 patients. The one-year mortality rate was 21.6% (n = 304). Mortality over the first two days reached 5.2% of all the patients; between Day 2 and Day 30, reached 5.3%; and between Day 31 and Day 365, reached 11.1%. Low Glasgow values, elevated lactate levels, elevated blood urea nitrogen (BUN) levels, low oxygen saturation, high respiratory rate, as well as being old and suffering from circulatory diseases and neurological diseases were risk factors for long-term mortality.

Conclusion:

The quick identification of patients at risk of long-term worsening could provide an opportunity to customize care through specific follow-up.
Introduction to Fatal Years 30 Years Later: New Research On Child Mortality in the Past Special Issue
Authors: Dribe Martin , Hacker J. David
Published: June 2023

2021 marked the 30-year anniversary of the publication Fatal Years: Child Mortality in the late Nineteenth-Century United States, a pioneering work in historical demography by Samuel H. Preston and Michael R. Haines. This special issue showcases the current state of historical mortality studies through a collection of articles originally presented at two commemorative sessions at the 2021 meeting of the Social Science History Association. It provides new and more nuanced evidence on several of the major themes of Fatal Years in terms of the mortality experience and includes studies of a wide range of contexts, from North America, to Ireland, England and Wales, and continental Europe. They all bring new evidence and leverage the dramatic development that has taken place in availability of large-scale micro-level data in the 30 years since Fatal Years was published. This introduction first provides some background to the collection and then summarizes the main findings from the different articles included. Preston and Haines provide a coda to this collection with a short reflection article on researching and writing Fatal Years.
Enuresis und nicht-organische (funktionelle) Harninkontinenz bei Kindern und Jugendlichen – klinische Leitlinie zur Diagnostik und Therapie
Authors: von Gontard Alexander , Kuwertz-Bröking Eberhard
Published: June 2023

Zusammenfassung: Hintergrund: Enuresis und Harninkontinenz tags sind häufige Störungen des Kindesalters, die mit einer hohen Beeinträchtigung und komorbiden psychischen Störungen einhergehen können. Das Ziel dieser interdisziplinären Leitlinie ist es, den aktuellen Stand zur Diagnostik und Therapie dieser Störungen aus somatischer und psychiatrischer Sicht zusammenzufassen und praxisorientierte Empfehlungen zu formulieren. Methoden: Die Leitliniengruppe setzte sich aus 18 Fachgesellschaften zusammen. Die Leitlinie wurde auf der Basis aktueller Literaturrecherchen in mehreren online erfolgten Abstimmungen und Konsensuskonferenzen nach den Regeln der Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V. (AWMF) verabschiedet. Ergebnisse: Nach der International Children’s Continence Society (ICCS) können vier Subformen der Enuresis (nocturna) und neun der funktionellen Harninkontinenz tags unterschieden werden. Organische Faktoren müssen ausgeschlossen werden. Eine klinische und nicht-invasive Diagnostik ist in den meisten Fällen ausreichend. Eine Standard-Urotherapie stellt die Grundlage der Behandlung dar. Sie kann durch eine spezifische Urotherapie ergänzt werden. Eine Pharmakotherapie kann vor allem bei der Enuresis und Dranginkontinenz sinnvoll sein. Komorbide psychische und somatische Störungen müssen berücksichtigt werden. Schlussfolgerungen: Im Konsensusverfahren konnten alle Empfehlungen mit hoher Zustimmung verabschiedet werden. Eine interdisziplinäre Zusammenarbeit ist von hoher Bedeutung, da somatische Faktoren und komorbide psychische Störungen und Symptome berücksichtigt werden müssen. Forschungsbedarf besteht vor allem bei der funktionellen Harninkontinenz tags.
Analytical and experimental study of a valveless piezoelectric micropump with high flowrate and pressure load
Authors: Ni Jiafeng , Xuan Weipeng , Li Yilin , Chen Jinkai , Li Wenjun , Cao Zhen , Dong Shurong , Jin Hao , Sun Lingling , Luo Jikui
Published: June 2023

Miniaturized gas pumps based on electromagnetic effect have been intensively studied and widely applied in industries. However, the electromagnetic effect-based gas pumps normally have large sizes, high levels of noises and high power consumption, thus they are not suitable for wearable/portable applications. Herein, we propose a high-flowrate and high-pressure load valveless piezoelectric micropump with dimensions of 16 mm*16 mm*5 mm. The working frequency, vibration mode and displacement of the piezoelectric actuator, the velocity of gas flow, and the volume flowrate of the micropump are analyzed using the finite element analysis method. The maximum vibration amplitude of the piezoelectric actuator reaches ~29.4 μm. The output gas flowrate of the pump is approximately 135 mL/min, and the maximum output pressure exceeds 40 kPa. Then, a prototype of the piezoelectric micropump is fabricated. Results show that performance of the micropump is highly consistent with the numerical analysis with a high flowrate and pressure load, demonstrated its great potential for wearable/portable applications, especially for blood pressure monitoring.
Wide-spread brain activation and reduced CSF flow during avian REM sleep
Authors: Ungurean Gianina , Behroozi Mehdi , Böger Leonard , Helluy Xavier , Libourel Paul-Antoine , Güntürkün Onur , Rattenborg Niels C.
Published: June 2023

Mammalian sleep has been implicated in maintaining a healthy extracellular environment in the brain. During wakefulness, neuronal activity leads to the accumulation of toxic proteins, which the glymphatic system is thought to clear by flushing cerebral spinal fluid (CSF) through the brain. In mice, this process occurs during non-rapid eye movement (NREM) sleep. In humans, ventricular CSF flow has also been shown to increase during NREM sleep, as visualized using functional magnetic resonance imaging (fMRI). The link between sleep and CSF flow has not been studied in birds before. Using fMRI of naturally sleeping pigeons, we show that REM sleep, a paradoxical state with wake-like brain activity, is accompanied by the activation of brain regions involved in processing visual information, including optic flow during flight. We further demonstrate that ventricular CSF flow increases during NREM sleep, relative to wakefulness, but drops sharply during REM sleep. Consequently, functions linked to brain activation during REM sleep might come at the expense of waste clearance during NREM sleep.
Self-healable polymer complex with a giant ionic thermoelectric effect
Authors: Kim Dong-Hu , Akbar Zico Alaia , Malik Yoga Trianzar , Jeon Ju-Won , Jang Sung-Yeon
Published: June 2023

In this study, we develop a stretchable/self-healable polymer, PEDOT:PAAMPSA:PA, with remarkably high ionic thermoelectric (iTE) properties: an ionic figure-of-merit of 12.3 at 70% relative humidity (RH). The iTE properties of PEDOT:PAAMPSA:PA are optimized by controlling the ion carrier concentration, ion diffusion coefficient, and Eastman entropy, and high stretchability and self-healing ability are achieved based on the dynamic interactions between the components. Moreover, the iTE properties are retained under repeated mechanical stress (30 cycles of self-healing and 50 cycles of stretching). An ionic thermoelectric capacitor (ITEC) device using PEDOT:PAAMPSA:PA achieves a maximum power output and energy density of 4.59 μW‧m−2 and 1.95 mJ‧m−2, respectively, at a load resistance of 10 KΩ, and a 9-pair ITEC module produces a voltage output of 0.37 V‧K−1 with a maximum power output of 0.21 μW‧m−2 and energy density of 0.35 mJ‧m−2 at 80% RH, demonstrating the potential for a self-powering source.
Complex tsunamigenic near-trench seafloor deformation during the 2011 Tohoku–Oki earthquake
Authors: Zhang Kai , Wang Yanru , Luo Yu , Zhao Dineng , Wang Mingwei , Yang Fanlin , Wu Ziyin
Published: June 2023

The near-trench coseismic rupture behaviour of the 2011 Tohoku–Oki earthquake remains poorly understood due to the scarcity of near-field observations. Differential bathymetry offers a unique approach to studying offshore coseismic seafloor deformation but has a limited horizontal resolution. Here we use differential bathymetry estimates with improved horizontal resolutions to investigate near-trench coseismic slip behaviours in the 2011 Tohoku–Oki earthquake. In the main rupture region, a velocity-strengthening behaviour in the shallow fault is observed. By contrast, the seafloor uplift decreases towards the trench, but the trend inverts near the backstop interface outcrop, revealing significant off-fault deformation features. Amongst various competing off-fault effects observed, we suggest that inelastic deformation plays a predominant role in near-trench tsunami excitation. Large trench-bleaching rupture is also observed immediately north of 39°, delimiting the northern extent of the main rupture region. Overall, striking spatial heterogeneity of the shallow rupture behaviour is revealed for the region.
Downregulation of extraembryonic tension controls body axis formation in avian embryos
Authors: Kunz Daniele , Wang Anfu , Chan Chon U , Pritchard Robyn H. , Wang Wenyu , Gallo Filomena , Bradshaw Charles R. , Terenzani Elisa , Müller Karin H. , Huang Yan Yan Shery , Xiong Fengzhu
Published: June 2023

Embryonic tissues undergoing shape change draw mechanical input from extraembryonic substrates. In avian eggs, the early blastoderm disk is under the tension of the vitelline membrane (VM). Here we report that the chicken VM characteristically downregulates tension and stiffness to facilitate stage-specific embryo morphogenesis. Experimental relaxation of the VM early in development impairs blastoderm expansion, while maintaining VM tension in later stages resists the convergence of the posterior body causing stalled elongation, failure of neural tube closure, and axis rupture. Biochemical and structural analysis shows that VM weakening is associated with the reduction of outer-layer glycoprotein fibers, which is caused by an increasing albumen pH due to CO2 release from the egg. Our results identify a previously unrecognized potential cause of body axis defects through mis-regulation of extraembryonic tissue tension.
Multiple ParA/MinD ATPases coordinate the positioning of disparate cargos in a bacterial cell
Authors: Pulianmackal Lisa T. , Limcaoco Jose Miguel I. , Ravi Keerthikka , Yang Sinyu , Zhang Jeffrey , Tran Mimi K. , Ghalmi Maria , O’Meara Matthew J. , Vecchiarelli Anthony G.
Published: June 2023

In eukaryotes, linear motor proteins govern intracellular transport and organization. In bacteria, where linear motors involved in spatial regulation are absent, the ParA/MinD family of ATPases organize an array of genetic- and protein-based cellular cargos. The positioning of these cargos has been independently investigated to varying degrees in several bacterial species. However, it remains unclear how multiple ParA/MinD ATPases can coordinate the positioning of diverse cargos in the same cell. Here, we find that over a third of sequenced bacterial genomes encode multiple ParA/MinD ATPases. We identify an organism (Halothiobacillus neapolitanus) with seven ParA/MinD ATPases, demonstrate that five of these are each dedicated to the spatial regulation of a single cellular cargo, and define potential specificity determinants for each system. Furthermore, we show how these positioning reactions can influence each other, stressing the importance of understanding how organelle trafficking, chromosome segregation, and cell division are coordinated in bacterial cells. Together, our data show how multiple ParA/MinD ATPases coexist and function to position a diverse set of fundamental cargos in the same bacterial cell.
Bacteriophage therapy against pathological Klebsiella pneumoniae ameliorates the course of primary sclerosing cholangitis
Authors: Ichikawa Masataka , Nakamoto Nobuhiro , Kredo-Russo Sharon , Weinstock Eyal , Weiner Iddo Nadav , Khabra Efrat , Ben-Ishai Noa , Inbar Dana , Kowalsman Noga , Mordoch Ron , Nicenboim Julian , Golembo Myriam , Zak Naomi , Jablonska Jagoda , Sberro-Livnat Hila , Navok Sharon , Buchshtab Nufar , Suzuki Takahiro , Miyamoto Kentaro , Teratani Toshiaki , Fujimori Sota , Aoto Yoshimasa , Konda Mikiko , Hayashi Naoki , Chu Po-Sung , Taniki Nobuhito , Morikawa Rei , Kasuga Ryosuke , Tabuchi Takaya , Sugimoto Shinya , Mikami Yohei , Shiota Atsushi , Bassan Merav , Kanai Takanori
Published: June 2023

Primary sclerosing cholangitis (PSC) is characterized by progressive biliary inflammation and fibrosis. Although gut commensals are associated with PSC, their causative roles and therapeutic strategies remain elusive. Here we detect abundant Klebsiella pneumoniae (Kp) and Enterococcus gallinarum in fecal samples from 45 PSC patients, regardless of intestinal complications. Carriers of both pathogens exhibit high disease activity and poor clinical outcomes. Colonization of PSC-derived Kp in specific pathogen-free (SPF) hepatobiliary injury-prone mice enhances hepatic Th17 cell responses and exacerbates liver injury through bacterial translocation to mesenteric lymph nodes. We developed a lytic phage cocktail that targets PSC-derived Kp with a sustained suppressive effect in vitro. Oral administration of the phage cocktail lowers Kp levels in Kp-colonized germ-free mice and SPF mice, without off-target dysbiosis. Furthermore, we demonstrate that oral and intravenous phage administration successfully suppresses Kp levels and attenuates liver inflammation and disease severity in hepatobiliary injury-prone SPF mice. These results collectively suggest that using a lytic phage cocktail shows promise for targeting Kp in PSC.
Hamster model for post-COVID-19 alveolar regeneration offers an opportunity to understand post-acute sequelae of SARS-CoV-2
Authors: Heydemann Laura , Ciurkiewicz Małgorzata , Beythien Georg , Becker Kathrin , Schughart Klaus , Stanelle-Bertram Stephanie , Schaumburg Berfin , Mounogou-Kouassi Nancy , Beck Sebastian , Zickler Martin , Kühnel Mark , Gabriel Gülsah , Beineke Andreas , Baumgärtner Wolfgang , Armando Federico
Published: June 2023

COVID-19 survivors often suffer from post-acute sequelae of SARS-CoV-2 infection (PASC). Current evidence suggests dysregulated alveolar regeneration as a possible explanation for respiratory PASC, which deserves further investigation in a suitable animal model. This study investigates morphological, phenotypical and transcriptomic features of alveolar regeneration in SARS-CoV-2 infected Syrian golden hamsters. We demonstrate that CK8+ alveolar differentiation intermediate (ADI) cells occur following SARS-CoV-2-induced diffuse alveolar damage. A subset of ADI cells shows nuclear accumulation of TP53 at 6- and 14-days post infection (dpi), indicating a prolonged arrest in the ADI state. Transcriptome data show high module scores for pathways involved in cell senescence, epithelial-mesenchymal transition, and angiogenesis in cell clusters with high ADI gene expression. Moreover, we show that multipotent CK14+ airway basal cell progenitors migrate out of terminal bronchioles, aiding alveolar regeneration. At 14 dpi, ADI cells, peribronchiolar proliferates, M2-macrophages, and sub-pleural fibrosis are observed, indicating incomplete alveolar restoration. The results demonstrate that the hamster model reliably phenocopies indicators of a dysregulated alveolar regeneration of COVID-19 patients. The results provide important information on a translational COVID-19 model, which is crucial for its application in future research addressing pathomechanisms of PASC and in testing of prophylactic and therapeutic approaches for this syndrome.
FAT-switch-based quantitative S-nitrosoproteomics reveals a key role of GSNOR1 in regulating ER functions
Authors: Qin Guochen , Qu Menghuan , Jia Bei , Wang Wei , Luo Zhuojun , Song Chun-Peng , Tao W. Andy , Wang Pengcheng
Published: June 2023

Reversible protein S-nitrosylation regulates a wide range of biological functions and physiological activities in plants. However, it is challenging to quantitively determine the S-nitrosylation targets and dynamics in vivo. In this study, we develop a highly sensitive and efficient fluorous affinity tag-switch (FAT-switch) chemical proteomics approach for S-nitrosylation peptide enrichment and detection. We quantitatively compare the global S-nitrosylation profiles in wild-type Arabidopsis and gsnor1/hot5/par2 mutant using this approach, and identify 2,121 S-nitrosylation peptides in 1,595 protein groups, including many previously unrevealed S-nitrosylated proteins. These are 408 S-nitrosylated sites in 360 protein groups showing an accumulation in hot5-4 mutant when compared to wild type. Biochemical and genetic validation reveal that S-nitrosylation at Cys337 in ER OXIDOREDUCTASE 1 (ERO1) causes the rearrangement of disulfide, resulting in enhanced ERO1 activity. This study offers a powerful and applicable tool for S-nitrosylation research, which provides valuable resources for studies on S-nitrosylation-regulated ER functions in plants.
ACL and HAT1 form a nuclear module to acetylate histone H4K5 and promote cell proliferation
Authors: Xu Qiutao , Yue Yaping , Liu Biao , Chen Zhengting , Ma Xuan , Wang Jing , Zhao Yu , Zhou Dao-Xiu
Published: June 2023

Acetyl-CoA utilized by histone acetyltransferases (HAT) for chromatin modification is mainly generated by ATP-citrate lyase (ACL) from glucose sources. How ACL locally establishes acetyl-CoA production for histone acetylation remains unclear. Here we show that ACL subunit A2 (ACLA2) is present in nuclear condensates, is required for nuclear acetyl-CoA accumulation and acetylation of specific histone lysine residues, and interacts with Histone AcetylTransferase1 (HAT1) in rice. The rice HAT1 acetylates histone H4K5 and H4K16 and its activity on H4K5 requires ACLA2. Mutations of rice ACLA2 and HAT1 (HAG704) genes impair cell division in developing endosperm, result in decreases of H4K5 acetylation at largely the same genomic regions, affect the expression of similar sets of genes, and lead to cell cycle S phase stagnation in the endosperm dividing nuclei. These results indicate that the HAT1-ACLA2 module selectively promotes histone lysine acetylation in specific genomic regions and unravel a mechanism of local acetyl-CoA production which couples energy metabolism with cell division.