bluuebunny/crossref_metadata_2025 huggingface dataset:
A total energy-based adaptive mesh refinement technique for the simulation of compressible flow
Authors: Xu Xian , Chen Yingchun , Han Zhirong , Zhou Feng
Published: May 2023

In this paper, an adaptive mesh refinement technique is presented for simulation of compressible flows, which can effectively refine the mesh in the regions with shock waves and vortices. The present approach uses the total energy per unit volume as an indicator to capture the shock waves and vortical structures. In the approach, an h-refinement strategy is adopted. To save the computational effort, the flow variables on the new mesh are obtained from the previous step by interpolation, which ensures that the problem is always solved on the refined mesh. Both inviscid and viscous compressible flows are considered in this work. Their governing equations are, respectively, Euler equations and Navier–Stokes equations associated with the implementation of the Spalart–Allmaras turbulence model. The cell-centered finite volume method and Jameson scheme are chosen to carry out spatial discretization, and the five-stage Runge–Kutta scheme is applied to discretize the temporal derivative. The present approach is applied to simulate three test problems for its validation. Numerical results show that it can effectively capture the shock waves and vortices with improvement in solution accuracy.
Gene expression and wildlife health: varied interpretations based on perspective
Authors: Bowen Lizabeth , Yee Julie , Bodkin James , Waters Shannon , Murray Michael , Coletti Heather , Ballachey Brenda , Monson Daniel , Miles A. Keith
Published: May 2023

We evaluated wildlife population health from the perspective of statistical means vs. variances. We outlined the choices necessary to provide the framework for our study. These consisted of spatial and temporal boundaries (e.g., choice of sentinel species, populations, time frame), measurement techniques (molecular to population level), and appropriate statistical analyses. We chose to assess the health of 19 sea otter populations, located in the north Pacific from the Aleutian Islands, AK, to Santa Barbara, CA, and varying in population growth rates and length of occupancy. Our focal metric was gene expression (i.e., mRNA transcripts) data that we had previously generated across sea otter populations as a measure of population health. We used statistical methods with different approaches (i.e., means vs. variances) and examined the subsequent interpretive outcomes and how these influence our assessment of “health.” Interpretations based on analyses using variances versus means overlapped to some degree. In general, sea otter populations with low variation in gene expression were limited by food resources and at or near carrying capacity. In populations where the variation in gene expression was moderate or high, four out of five populations were increasing in abundance, or had been recently increasing. Where we had additional information on sources of stressors at the level of the population, we were able to draw inferences from those stressors to specific gene expression results. For example, gene expression patterns of sea otters from Western Prince William Sound were consistent with long term exposure to petroleum hydrocarbons, whereas in Kachemak Bay, patterns were consistent with exposure to algal toxins. Ultimately, determination of population or ecosystem health will be most informative when multiple metrics are examined across disciplines in the context of specific scenarios and goals.
Pore density of the benthic foraminiferal test responded to the hypoxia off the Changjiang estuary in the East China Sea
Authors: Wang Feifei , Yang Shixiong , Zhai Bin , Gong Shaojun , Wang Junjie , Fu Xiaojin , Yi Jian , Ning Ze
Published: May 2023

The benthic foraminiferal assemblages are commonly used to indicate different oxygenation conditions. In the last few decades, pore characteristics of the benthic foraminiferal tests from the micro-perspective using high-spatial-resolution analysis have been extensively suggested to indicate redox changes. Based on the whole test of the living shallow-infaunal species Bolivina robusta using a more representative and comprehensive method, we observed a significant negative correlation between the pore density (PD) and bottom dissolved oxygen (DO) concentration, and the average PD was about 36% higher in hypoxic environments (DO<3 mg/l) than in oxic environments (DO>3 mg/l). In terms of reproduction pattern in hypoxic environments, the species seemed to mainly choose the asexual life cycle (74.60%) to get more small generations with larger pore size (PS) (asexual 7 μm vs. sexual 4 μm) and exterior ornamentation (irregular papillae) as their survival strategy. The results provide new insight into the benthic foraminiferal ecology to reconstruct the pale-oceanography and paleo-ecology changes in the East China Sea. Moreover, this study has the potential to be applied in broad regions as an independent proxy by comparison to other widely-distributed benthic foraminiferal species.
Research on inertia transfer in load simulation of tracked vehicle under complex working conditions
Authors: Lv Gang , Lv Haoliang , Chen Zhaomeng , Chu Wei , Mao Jiliang
Published: May 2023

At present, research on the loading simulation test bench for overloaded vehicles is mostly limited to the realization of loading simulation under the condition of straight line driving of the vehicle. When simulating the whole vehicle load under straight line driving condition, only accurate road load and inertial load can be obtained to achieve accurate load simulation, and the inertial load required to be simulated by each side device is half of the whole vehicle inertial load. However, straight line driving is only the most ideal driving. The real driving conditions (including ground conditions) of the vehicle are usually composed of steering, longitudinal slope, lateral slope and different ground adhesion coefficients. Therefore, the loads borne by the two independent load simulation systems located on both sides of the vehicle may be different during the load simulation process. In addition, the frequency characteristics of the loads to be simulated by the same side load simulation device at different time sequences may also be different. This paper studies the dynamics modeling, load distribution and error compensation in the whole vehicle load simulation process in order to achieve accurate crawler vehicle load simulation from three aspects.
A proposal to analyze the progression of non-dialytic chronic kidney disease by surrogate endpoints: introducing parametric survival models
Authors: Erohildes Ferreira Renato , Sanders-Pinheiro Helady , Basile Colugnati Fernando Antonio
Published: May 2023

Introduction

Chronic kidney disease (CDK) progression studies increasingly use surrogate endpoints based on the estimated glomerular filtration rate. The clinical characteristics of these endpoints bring new challenges in comparing groups of patients, as traditional Cox models may lead to biased estimates mainly because they do not assume a hazard function.

Objective

This study proposes the use of parametric survival analysis models with the three most commonly used endpoints in nephrology based on a case study. Estimated glomerular filtration rate (eGFR) decay > 5 mL/year, eGFR decline > 30%, and change in CKD stage were evaluated.

Method

The case study is a 5-year retrospective cohort study that enrolled 778 patients in the predialysis stage. Exponential, Weibull, Gompertz, lognormal, and logistic models were compared, and proportional hazard and accelerated failure time (AFT) models were evaluated.

Results

The endpoints had quite different hazard functions, demonstrating the importance of choosing appropriate models for each. AFT models were more suitable for the clinical interpretation of the effects of covariates on these endpoints.

Conclusion

Surrogate endpoints have different hazard distributions over time, which is already recognized by nephrologists. More flexible analysis techniques that capture these relevant clinical characteristics in decision-making should be encouraged and disseminated in nephrology research.
Epilepsy in a mouse model of GNB1 encephalopathy arises from altered potassium (GIRK) channel signaling and is alleviated by a GIRK inhibitor
Authors: Colombo Sophie , Reddy Haritha P. , Petri Sabrina , Williams Damian J. , Shalomov Boris , Dhindsa Ryan S. , Gelfman Sahar , Krizay Daniel , Bera Amal K. , Yang Mu , Peng Yueqing , Makinson Christopher D. , Boland Michael J. , Frankel Wayne N. , Goldstein David B. , Dascal Nathan
Published: May 2023

De novo mutations in GNB1, encoding the Gβ1 subunit of G proteins, cause a neurodevelopmental disorder with global developmental delay and epilepsy, GNB1 encephalopathy. Here, we show that mice carrying a pathogenic mutation, K78R, recapitulate aspects of the disorder, including developmental delay and generalized seizures. Cultured mutant cortical neurons also display aberrant bursting activity on multi-electrode arrays. Strikingly, the antiepileptic drug ethosuximide (ETX) restores normal neuronal network behavior in vitro and suppresses spike-and-wave discharges (SWD) in vivo. ETX is a known blocker of T-type voltage-gated Ca2+ channels and G protein-coupled potassium (GIRK) channels. Accordingly, we present evidence that K78R results in a gain-of-function (GoF) effect by increasing the activation of GIRK channels in cultured neurons and a heterologous model (Xenopus oocytes)—an effect we show can be potently inhibited by ETX. This work implicates a GoF mechanism for GIRK channels in epilepsy, identifies a new mechanism of action for ETX in preventing seizures, and establishes this mouse model as a pre-clinical tool for translational research with predicative value for GNB1 encephalopathy.
Association of LIPC polymorphisms with stroke risk in the Chinese population
Authors: Pan Jiaxing , Zhuo Qingqing , Chen Xu , Huang Xuehong , Shen Shiqiang , Yang Qiu , Luo Jiawen , Wang Suiyan , Jin Tianbo
Published: May 2023

Background

Stroke is a common cerebrovascular disease. The purpose of this study was to explore the association between LIPC single nucleotide polymorphisms (SNPs) and the risk of stroke in the Chinese population.

Methods

This study recruited 710 stroke patients and 701 healthy controls. The four SNPs (rs690, rs6083, rs3829461, and rs6074) in LIPC were genotyped by the Agena MassARRAY. The correlation between LIPC polymorphisms and stroke risk was measured by odds ratio (OR) and 95% confidence interval (CI). In addition, multifactor dimensionality reduction (MDR) analysis was used to evaluate the impact of SNP–SNP interaction on stroke risk.

Results

Overall analysis showed that rs690 was associated with an increased risk of stroke (T vs. G: OR = 1.19, 95% CI: 1.01–1.40, p = 0.041; additive: OR = 1.20, 95% CI: 1.01–1.42, p = 0.036). The stratified analysis revealed that rs690 was associated with an increased risk of stroke in subjects aged ≤ 64 years, male patients, and smokers, and rs6074 was associated with an increased risk of stroke in subjects aged > 64 years, male patients, drinkers, and non-smokers (p < 0.05). The results of the MDR analysis suggested the four-locus model as the most favorable model for assessing the risk of stroke. The analysis of clinical parameters of stroke patients showed that rs690 was correlated with platelet distribution width (PDW) (p = 0.014) and hematocrit levels (p = 0.004), and rs6074 was correlated with low-density lipoprotein cholesterol (LDL-C) level (p = 0.033). Furthermore, bioinformatics analysis results demonstrated that the expression levels of LIPC and its related genes (APOB, CETP, PNPLA2, and LMF1) were significantly different between the control and stroke groups (p < 0.05), and LIPC-related proteins were mainly related to lipid metabolism.

Conclusion

This study indicated that rs690 and rs6074 in LIPC were significantly associated with increased risk of stroke in the Chinese population, possibly by regulating the levels of PDW, HCT, and LDL-C.
Development and validation for multifactor prediction model of sudden sensorineural hearing loss
Authors: Zeng Chaojun , Yang Yunhua , Huang Shuna , He Wenjuan , Cai Zhang , Huang Dongdong , Lin Chang , Chen Junying
Published: May 2023

Background

Sudden sensorineural hearing loss (SSNHL) is a global problem threatening human health. Early and rapid diagnosis contributes to effective treatment. However, there is a lack of effective SSNHL prediction models.

Methods

A retrospective study of SSNHL patients from Fujian Geriatric Hospital (the development cohort with 77 participants) was conducted and data from First Hospital of Putian City (the validation cohort with 57 participants) from January 2018 to December 2021 were validated. Basic characteristics and the results of the conventional coagulation test (CCT) and the blood routine test (BRT) were then evaluated. Binary logistic regression was used to develop a prediction model to identify variables significantly associated with SSNHL, which were then included in the nomogram. The discrimination and calibration ability of the nomogram was evaluated by receiver operating characteristic (ROC), calibration plot, and decision curve analysis both in the development and validation cohorts. Delong’s test was used to calculate the difference in ROC curves between the two cohorts.

Results

Thrombin time (TT), red blood cell (RBC), and granulocyte–lymphocyte ratio (GLR) were found to be associated with the diagnosis of SSNHL. A prediction nomogram was constructed using these three predictors. The AUC in the development and validation cohorts was 0.871 (95% CI: 0.789–0.953) and 0.759 (95% CI: 0.635–0.883), respectively. Delong’s test showed no significant difference in the ROC curves between the two groups (D = 1.482, p = 0.141).

Conclusion

In this study, a multifactor prediction model for SSNHL was established and validated. The factors included in the model could be easily and quickly accessed, which could help physicians make early diagnosis and clinical treatment decisions.
Case report: Bilateral double beta peak activity is influenced by stimulation, levodopa concentrations, and motor tasks, in a Parkinson’s disease patient on chronic deep brain stimulation
Authors: Giannini Giulia , Baldelli Luca , Leogrande Gaetano , Cani Ilaria , Mantovani Paolo , Lopane Giovanna , Cortelli Pietro , Calandra-Buonaura Giovanna , Conti Alfredo
Published: May 2023

Introduction

Subthalamic (STN) local field potentials (LFPs) in the beta band are considered potential biomarkers for closed-loop deep brain stimulation (DBS) in Parkinson’s disease (PD). The beta band is further dissected into low-and high-frequency components with somewhat different functions, although their concomitance and association in the single patient is far to be defined. We present a 56-year-old male PD patient undergoing DBS showing a double-beta peak activity on both sides. The aim of the study was to investigate how low-and high-beta peaks were influenced by plasma levodopa (L-dopa) levels, stimulation, and motor performances.

Methods

A systematic evaluation of raw LFPs, plasma L-dopa levels, and motor tasks was performed in the following four conditions: OFF medications/ON stimulation, OFF medications/OFF stimulation, ON medications/OFF stimulation, and ON medications/ON stimulation.

Results

The analysis of the LFP spectra suggests the following results: (1) the high-beta peak was suppressed by stimulation, while the low-beta peak showed a partial and not consistent response to stimulation; (2) the high-beta peak is also influenced by plasma L-dopa concentration, showing a progressive amplitude increment concordant with plasma L-dopa levels, while the low-beta peak shows a different behavir; and (3) motor performances seem to impact beta peaks behavior.

Conclusion

This single exploratory case study illustrates a complex behavior of low-and high-beta peaks in a PD patient, in response to stimulation, L-dopa plasma levels, and motor performances. Our results suggest the importance to investigate patient-specific individual LFP patterns in view of upcoming closed-loop stimulation.
FAIR in action: Brain-CODE - A neuroscience data sharing platform to accelerate brain research
Authors: Behan Brendan , Jeanson Francis , Cheema Heena , Eng Derek , Khimji Fatema , Vaccarino Anthony L. , Gee Tom , Evans Susan G. , MacPhee F. Chris , Dong Fan , Shahnazari Shahab , Sparks Alana , Martens Emily , Lasalandra Bianca , Arnott Stephen R. , Strother Stephen C. , Javadi Mojib , Dharsee Moyez , Evans Kenneth R. , Nylen Kirk , Mikkelsen Tom
Published: May 2023

The effective sharing of health research data within the healthcare ecosystem can have tremendous impact on the advancement of disease understanding, prevention, treatment, and monitoring. By combining and reusing health research data, increasingly rich insights can be made about patients and populations that feed back into the health system resulting in more effective best practices and better patient outcomes. To achieve the promise of a learning health system, data needs to meet the FAIR principles of findability, accessibility, interoperability, and reusability. Since the inception of the Brain-CODE platform and services in 2012, the Ontario Brain Institute (OBI) has pioneered data sharing activities aligned with FAIR principles in neuroscience. Here, we describe how Brain-CODE has operationalized data sharing according to the FAIR principles. Findable—Brain-CODE offers an interactive and itemized approach for requesters to generate data cuts of interest that align with their research questions. Accessible—Brain-CODE offers multiple data access mechanisms. These mechanisms—that distinguish between metadata access, data access within a secure computing environment on Brain-CODE and data access via export will be discussed. Interoperable—Standardization happens at the data capture level and the data release stage to allow integration with similar data elements. Reusable - Brain-CODE implements several quality assurances measures and controls to maximize data value for reusability. We will highlight the successes and challenges of a FAIR-focused neuroinformatics platform that facilitates the widespread collection and sharing of neuroscience research data for learning health systems.
Brain subnetworks most sensitive to alterations of functional connectivity in Schizophrenia: a data-driven approach
Authors: Keyvanfard Farzaneh , Nasab Alireza Rahimi , Nasiraei-Moghaddam Abbas
Published: May 2023

Functional connectivity (FC) of the brain changes in various brain disorders. Its complexity, however, makes it difficult to obtain a systematic understanding of these alterations, especially when they are found individually and through hypothesis-based methods. It would be easier if the variety of brain connectivity alterations is extracted through data-driven approaches and expressed as variation modules (subnetworks). In the present study, we modified a blind approach to determine inter-group brain variations at the network level and applied it specifically to schizophrenia (SZ) disorder. The analysis is based on the application of independent component analysis (ICA) over the subject's dimension of the FC matrices, obtained from resting-state functional magnetic resonance imaging (rs-fMRI). The dataset included 27 SZ people and 27 completely matched healthy controls (HC). This hypothesis-free approach led to the finding of three brain subnetworks significantly discriminating SZ from HC. The area associated with these subnetworks mostly covers regions in visual, ventral attention, and somatomotor areas, which are in line with previous studies. Moreover, from the graph perspective, significant differences were observed between SZ and HC for these subnetworks, while there was no significant difference when the same parameters (path length, network strength, global/local efficiency, and clustering coefficient) across the same limited data were calculated for the whole brain network. The increased sensitivity of those subnetworks to SZ-induced alterations of connectivity suggested whether an individual scoring method based on their connectivity values can be applied to classify subjects. A simple scoring classifier was then suggested based on two of these subnetworks and resulted in acceptable sensitivity and specificity with an area under the ROC curve of 77.5%. The third subnetwork was found to be a less specific building block (module) for describing SZ alterations. It projected a wider range of inter-individual variations and, therefore, had a lower chance to be considered as a SZ biomarker. These findings confirmed that investigating brain variations from a modular viewpoint can help to find subnetworks that are more sensitive to SZ-induced alterations. Altogether, our study results illustrated the developed method's ability to systematically find brain alterations caused by SZ disorder from a network perspective.
Clinical spectrum of contactin-associated protein 2 autoimmune encephalitis in children
Authors: Hu Wenjing , Wang Enhui , Fang Hongjun , Li Li , Yi Jurong , Liu Qingqing , Qing Wei , Guo Danni , Tan Qianqian , Liao Hongmei
Published: May 2023

Objective

Anti-contactin-associated protein 2 (CASPR2)-related autoimmune encephalitis (AE) is more common in adults than in children. Clinical understanding of anti-CASPR2-antibody (Ab)-related AE, diagnosis and treatment standards are lacking in children. Therefore, this retrospective study on clinical symptoms and treatment outcomes in children with anti-CASPR2-Ab-related AE was conducted, to improve the clinical understanding of the disease, its diagnosis and treatment.

Methods

This study retrospectively assessed children with anti-CASPR2-Ab-related AE from January 1, 2020, to June 30, 2022, in the Department of Neurology at Hunan Children’s Hospital. Data regarding demographics, clinical symptoms, laboratory examinations, electroencephalography (EEG), imaging, and curative were collected.

Results

Thirteen patients were positive for serum anti-CASPR2-Ab (age at manifestation, 25 months to 13 years old; median, 8.1 years old; male-to-female ratio, 8/5). One patient (P1) had dual Abs, including anti-CASPR2 and anti-N-methyl-D-aspartate receptor Abs; his symptoms were more severe than those of children with anti-CASPR2 Abs alone. The clinical symptoms of the 13 patients with anti-CASPR2 Ab were movement disorders (9/13), consciousness disorders (9/13), abnormal demeanor (8/13), seizures (7/13), language disorders (6/13), fever (6/13), pain (4/13), involuntary exercise (4/13), poor diet (4/13), vomiting (3/13), sleep disorders (3/13), mood disorders (3/13), eczema/itching/redness (2/13), sweating (P8), urinary disorders (P13), and cognitive disorders (P9). No tumors were found in any patient. Additionally, EEG results of six patients were abnormal and imaging findings such as abnormal signals were found in 10 patients. Moreover, all except one patient recovered well after treatment; P1 with overlapping syndrome underwent recovery for more than 2 years. None of the patients who recovered have had a relapse.

Discussion and conclusion

Anti-CASPR2-Ab-related AE has several clinical manifestations. Anti-CASPR2-Ab levels were higher in male patients than in female patients. Moreover, related tumors are relatively rare. Most patients benefit from immunotherapy and have a lower chance of recurrence in the short term. Furthermore, different from patients who had anti-CASPR2-Ab AE alone, those with overlapping syndrome had a severe and complex condition requiring lengthy treatment and rehabilitation. Additional studies are needed to evaluate the long-term prognosis of these patients.
An fMRI study of finger movements in children with and without dyslexia
Authors: Turesky Ted K. , Luetje Megan M. , Eden Guinevere F.
Published: May 2023

Introduction

Developmental dyslexia is a language-based reading disability, yet some have reported motor impairments, usually attributed to cerebellar dysfunction.

Methods

Using fMRI, we compared children with and without dyslexia during irregularly paced, left or right-hand finger tapping. Next, we examined seed-to-voxel intrinsic functional connectivity (iFC) using six seed regions of the motor system (left and right anterior lobe of the cerebellum, SM1 and SMA).

Results

A whole-brain task-evoked analysis revealed relatively less activation in the group with dyslexia in right anterior cerebellum during right hand tapping. For iFC, we found the group with dyslexia to have greater iFC between the right SM1 seed and a medial aspect of right postcentral gyrus for left hand tapping; and greater iFC between the left SM1 seed and left thalamus, as well as weaker local iFC around the left SM1 seed region for right hand tapping. Lastly, extracted activity and connectivity values that had been identified in these between-group comparisons were not correlated with measures of reading.

Discussion

We conclude that there are some aberrations in motor system function in children with dyslexia, but these are not tied to reading ability.
Retinal ganglion cells undergo cell type—specific functional changes in a computational model of cone-mediated retinal degeneration
Authors: Xu Aiwen , Beyeler Michael
Published: May 2023

Introduction

Understanding the retina in health and disease is a key issue for neuroscience and neuroengineering applications such as retinal prostheses. During degeneration, the retinal network undergoes complex and multi-stage neuroanatomical alterations, which drastically impact the retinal ganglion cell (RGC) response and are of clinical importance. Here we present a biophysically detailed in silico model of the cone pathway in the retina that simulates the network-level response to both light and electrical stimulation.

Methods

The model included 11, 138 cells belonging to nine different cell types (cone photoreceptors, horizontal cells, ON/OFF bipolar cells, ON/OFF amacrine cells, and ON/OFF ganglion cells) confined to a 300 × 300 × 210μm patch of the parafoveal retina. After verifying that the model reproduced seminal findings about the light response of retinal ganglion cells (RGCs), we systematically introduced anatomical and neurophysiological changes (e.g., reduced light sensitivity of photoreceptor, cell death, cell migration) to the network and studied their effect on network activity.

Results

The model was not only able to reproduce common findings about RGC activity in the degenerated retina, such as hyperactivity and increased electrical thresholds, but also offers testable predictions about the underlying neuroanatomical mechanisms.

Discussion

Overall, our findings demonstrate how biophysical changes typified by cone-mediated retinal degeneration may impact retinal responses to light and electrical stimulation. These insights may further our understanding of retinal processing and inform the design of retinal prostheses.
Modulation of cerebellar cortical, cerebellar nuclear and vestibular nuclear activity using alternating electric currents
Authors: Avlar Billur , Rahman Ramia , Vendidandi Sai , Cetinkaya Esma , Asan Ahmet S. , Sahin Mesut , Lang Eric J.
Published: May 2023

Introduction

Cerebellar transcranial alternating current stimulation (ctACS) has shown promise as a therapeutic modality for treating a variety of neurological disorders, and for affecting normal learning processes. Yet, little is known about how electric fields induced by applied currents affect cerebellar activity in the mammalian cerebellum under in vivo conditions.

Methods

Alternating current (AC) stimulation with frequencies from 0.5 to 20 Hz was applied to the surface of the cerebellum in anesthetized rats. Extracellular recordings were obtained from Purkinje cells (PC), cerebellar and vestibular nuclear neurons, and other cerebellar cortical neurons.

Results and discussion

AC stimulation modulated the activity of all classes of neurons. Cerebellar and vestibular nuclear neurons most often showed increased spike activity during the negative phase of the AC stimulation. Purkinje cell simple spike activity was also increased during the negative phase at most locations, except for the cortex directly below the stimulus electrode, where activity was most often increased during the positive phase of the AC cycle. Other cortical neurons showed a more mixed, generally weaker pattern of modulation. The patterns of Purkinje cell responses suggest that AC stimulation induces a complex electrical field with changes in amplitude and orientation between local regions that may reflect the folding of the cerebellar cortex. Direct measurements of the induced electric field show that it deviates significantly from the theoretically predicted radial field for an isotropic, homogeneous medium, in both its orientation and magnitude. These results have relevance for models of the electric field induced in the cerebellum by AC stimulation.
Dynamics and consequences of nutrition-related microbial dysbiosis in early life: study protocol of the VITERBI GUT project
Authors: Tamarelle Jeanne , Creze Margaux M. , Savathdy Vanthanom , Phonekeo Sengrloun , Wallenborn Jordyn , Siengsounthone Latsamy , Fink Günther , Odermatt Peter , Kounnavong Sengchanh , Sayasone Somphou , Vonaesch Pascale
Published: May 2023

Introduction

Early life under- and overnutrition (jointly termed malnutrition) is increasingly recognized as an important risk factor for adult obesity and metabolic syndrome, a diet-related cluster of conditions including high blood sugar, fat and cholesterol. Nevertheless, the exact factors linking early life malnutrition with metabolic syndrome remain poorly characterized. We hypothesize that the microbiota plays a crucial role in this trajectory and that the pathophysiological mechanisms underlying under- and overnutrition are, to some extent, shared. We further hypothesize that a “dysbiotic seed microbiota” is transmitted to children during the birth process, altering the children’s microbiota composition and metabolic health. The overall objective of this project is to understand the precise causes and biological mechanisms linking prenatal or early life under- or overnutrition with the predisposition to develop overnutrition and/or metabolic disease in later life, as well as to investigate the possibility of a dysbiotic seed microbiota inheritance in the context of maternal malnutrition.

Methods/design

VITERBI GUT is a prospective birth cohort allowing to study the link between early life malnutrition, the microbiota and metabolic health. VITERBI GUT will include 100 undernourished, 100 normally nourished and 100 overnourished pregnant women living in Vientiane, Lao People’s Democratic Republic (PDR). Women will be recruited during their third trimester of pregnancy and followed with their child until its second birthday. Anthropometric, clinical, metabolic and nutritional data are collected from both the mother and the child. The microbiota composition of maternal and child’s fecal and oral samples as well as maternal vaginal and breast milk samples will be determined using amplicon and shotgun metagenomic sequencing. Epigenetic modifications and lipid profiles will be assessed in the child’s blood at 2 years of age. We will investigate for possible associations between metabolic health, epigenetics, and microbial changes.

Discussion

We expect the VITERBI GUT project to contribute to the emerging literature linking the early life microbiota, epigenetic changes and growth/metabolic health. We also expect this project to give new (molecular) insights into the mechanisms linking malnutrition-induced early life dysbiosis and metabolic health in later life, opening new avenues for microbiota-engineering using microbiota-targeted interventions.
Pituitary adenoma with cavernous sinus compartment penetration and intracranial extension: surgical anatomy, approach, and outcomes
Authors: Yang FuMing , Bi YunKe , Zhou QiangYi , Li HongChan , Xue YaJun , Zhu QingWei , Yin Jian , Wang ZhiYu , Lou MeiQing
Published: May 2023

Objectives

To understand the different characteristics and growth corridors of knosp grade 4 pituitary adenomas (Knosp4PA) with cavernous sinus (CS) compartments penetration and intracranial extension, aiming to improve the safety, effectiveness, and total resection rate of surgery.

Methods

A case series of 120 Knosp4PA patients with 187 invaded compartments were retrospectively reviewed. A novel surgery-relevant grading system was proposed according to the CS penetrating features. The details of approach drafting, risk prediction, and complication avoidance were analyzed and integrated through illustrated cases.

Results

All enrolled tumor was Knosp4PA which was derived from Knosp subgrades 3A(62.5%) and 3B(37.5%). Based on the tumor growth pathway and its relevant features, five subclassifications of intracranial extension(n=98,81.7%) were classified, which derived from the superior (Dolenc’s and Oculomotor subtype, 5% and 24.2%), lateral (Parkinson’s subtype,18.3%), and posterior (cerebral peduncle and Dorello’s subtype, 5.8% and 1.7%) CS compartment penetration. The size of intracranial extension is assessed by Lou’s scale proposed here based on preoperative MRI characteristics. Under Lou’s scale, the gross total rate (GTR) decreased (82%, 53%, 22%, and 19%) with grades increased (grade 0,1,2,3, respectively), and presents significant difference between the four groups (p=0.000), as well as between single and multiple compartments involved (p=0.001). Preoperative cranial nerve deficits included the optic nerve (53%), oculomotor nerve (24.2%), and abducent nerve (4.2%), with an overall rate of visual function improvement in 68.1%. Postoperative complications of transient diabetes insipidus, cerebrospinal fluid (CSF) leakage, and cranial nerve deficits were 6.7%, 0.8%, and 0%. No new cranial nerve deficits occurred. The mortality rate was 0.8%.

Conclusion

The concept of “penetration” refines the extracavernous growth pattern, and the five intracranial subclassifications help to understand the potential extension corridors, enhancing adequate exposure and targeted resection of Knosp4PA. This grading system may benefit from its predictive and prognostic value, from which a higher GTR rate can be achieved.
Clinical target volume and organs at risk segmentation for rectal cancer radiotherapy using the Flex U-Net network
Authors: Sha Xue , Wang Hui , Sha Hui , Xie Lu , Zhou Qichao , Zhang Wei , Yin Yong
Published: May 2023

Purpose/Objective(s)

The aim of this study was to improve the accuracy of the clinical target volume (CTV) and organs at risk (OARs) segmentation for rectal cancer preoperative radiotherapy.

Materials/Methods

Computed tomography (CT) scans from 265 rectal cancer patients treated at our institution were collected to train and validate automatic contouring models. The regions of CTV and OARs were delineated by experienced radiologists as the ground truth. We improved the conventional U-Net and proposed Flex U-Net, which used a register model to correct the noise caused by manual annotation, thus refining the performance of the automatic segmentation model. Then, we compared its performance with that of U-Net and V-Net. The Dice similarity coefficient (DSC), Hausdorff distance (HD), and average symmetric surface distance (ASSD) were calculated for quantitative evaluation purposes. With a Wilcoxon signed-rank test, we found that the differences between our method and the baseline were statistically significant (P< 0.05).

Results

Our proposed framework achieved DSC values of 0.817 ± 0.071, 0.930 ± 0.076, 0.927 ± 0.03, and 0.925 ± 0.03 for CTV, the bladder, Femur head-L and Femur head-R, respectively. Conversely, the baseline results were 0.803 ± 0.082, 0.917 ± 0.105, 0.923 ± 0.03 and 0.917 ± 0.03, respectively.

Conclusion

In conclusion, our proposed Flex U-Net can enable satisfactory CTV and OAR segmentation for rectal cancer and yield superior performance compared to conventional methods. This method provides an automatic, fast and consistent solution for CTV and OAR segmentation and exhibits potential to be widely applied for radiation therapy planning for a variety of cancers.
Pros and cons of streamlining and use of computerised clinical decision support systems to future-proof oncological multidisciplinary team meetings
Authors: Walraven Janneke E. W. , Verhoeven Rob H. A. , van der Hoeven Jacobus J. M. , van der Meulen Renske , Lemmens Valery E. P. P. , Hesselink Gijs , Desar Ingrid M. E.
Published: May 2023

Introduction

Nowadays nearly every patient with cancer is discussed in a multidisciplinary team meeting (MDTM) to determine an optimal treatment plan. The growth in the number of patients to be discussed is unsustainable. Streamlining and use of computerised clinical decision support systems (CCDSSs) are two major ways to restructure MDTMs. Streamlining is the process of selecting the patients who need to be discussed and in which type of MDTM. Using CCDSSs, patient data is automatically loaded into the minutes and a guideline-based treatment proposal is generated. We aimed to identify the pros and cons of streamlining and CCDSSs.

Methods

Semi-structured interviews were conducted with Dutch MDTM participants. With purposive sampling we maximised variation in participants’ characteristics. Interview data were thematically analysed.

Results

Thirty-five interviews were analysed. All interviewees agreed on the need to change the current MDTM workflow. Streamlining suggestions were thematised based on standard and complex cases and the location of the MDTM (i.e. local, regional or nationwide). Interviewees suggested easing the pressure on MDTMs by discussing standard cases briefly, not at all, or outside the MDTM with only two to three specialists. Complex cases should be discussed in tumour-type-specific regional MDTMs and highly complex cases by regional/nationwide expert teams. Categorizing patients as standard or complex was found to be the greatest challenge of streamlining. CCDSSs were recognised as promising, although none of the interviewees had made use of them. The assumed advantage was their capacity to generate protocolised treatment proposals based on automatically uploaded patient data, to unify treatment proposals and to facilitate research. However, they were thought to limit the freedom to deviate from the treatment advice.

Conclusion

To make oncological MDTMs sustainable, methods of streamlining should be developed and introduced. Physicians still have doubts about the value of CCDSSs.
Performing crisis to create your enemy: Europe vs. the EU in Hungarian populist discourse
Authors: Sata Robert
Published: May 2023

Hungary has become the leader of democratic backsliding within Europe, with Prime Minister Viktor Orbán turning into the staunchest critic of the EU, despite a consistent support for the European project among the wider public and Hungary being a net benefiter of EU membership. Using a systematic analysis of all speeches, statements and interviews of the PM for his three consecutive governments 2010–2022, I claim the radicalization of this Eurosceptic discourse is a direct consequence of a continuous populist performance of crisis that demands the creation of images of friends and foes to unite and mobilize people. Orbán relies on discursive processes of othering to construct to his liking both “the good people” and its enemies, who are to be blamed for the crises. Anybody can become an enemy in the various crises that follow each other. At the same time, discursive conceptions of Europe vs. the EU remain in the center of the discourse to establish Hungary's European belonging as well as opposition to EU for policies that allegedly people reject. While the economic crisis pits an economic “us” against the former socialist political elite, foreign capital, and the EU and IMF that are all blamed for Hungary's near-bankruptcy situation. The refugee crisis redefines both “us” and “others”, the “self” is distinguished using ethno-linguistic criteria and identitarian Christianity to signal the cultural distance from the Muslim migrant “other” as well as multicultural EU. The pandemic crisis is performed only to further exacerbate the conflict between the illiberal “self” and the liberal “others”, where supranational EU, promoting multiculturalism, gender ideology or neoliberal policies not only threatens the very existence of traditional-national lifestyles but endangers the people themselves. With each crisis performed, newer and newer conflict lines between various “European self's” and “threatening EU” are identified, each adding to the radicalization of Orbán's discourse. The demonization of the EU and the pretext of saving Europe using these false discursive constructs enables Orbán strengthen his grip of power and drift to authoritarianism.
“I don’t want to be a victim again”: the impact of repeat assault on police officers
Authors: Davidson Louise , Dennis Amelia , Theodoropoulou Andriana , Carter Holly , Amlôt Richard , Hesketh Ian
Published: May 2023

Introduction

The frequency of assaults on police officers in the United Kingdom is rising and evidence suggests that exposure to work-place violence can negatively impact wellbeing, for example, increased perceived stress, feeling worn out and tired, and emotional exhaustion. Despite the prevalence of assaults on police officers, little research has examined the impact of repeat assaults on officers’ wellbeing.

Method

For the current study, 12 semi-structured interviews were conducted to investigate the impact of repeat assaults on wellbeing and occupational outcomes in police officers and staff, including impacts on their mental and physical heath, impacts on their work, the impact of prior assaults on future assaults, and what support they were provided with.

Results

Findings indicate that repeat assaults had a negative impact on participants mental and physical wellbeing. Furthermore, a lack of support both from management and peers within the police force was found to further exacerbate the impact of repeat assaults. However, the provision of support was also identified as a mitigating factor when it was available and provided to participants which helped to protect participants from some of the negative impact of repeat assaults.

Discussion

Findings provide a unique in-depth perspective into police officers’ experiences following repeat assaults, which can in turn inform national policies and help tailor effective support services within the police force.
Aging engineers’ occupational self-efficacy—a mixed methods study
Authors: Wallin Stina , Fjellman-Wiklund Anncristine , Fagerström Lisbeth
Published: May 2023

Introduction

Engineers’ work has become more complex with increased demands in today’s changing working life. Self-efficacy is essential to successfully adapt to work-related changes and to cope with adverse job demands. However, less is known about aging engineers’ occupational self-efficacy. Therefore, this study explores facilitators and barriers to aging engineers’ occupational self-efficacy beliefs to continue working until expected retirement age. An additional purpose is to explore if any of the aspects described by the engineers are more prominent.

Methods

The study design was exploratory, using mixed methods with a qualitative to quantitative approach. A total of 125 engineers, aged between 45 and 65 years, answered two open-ended survey questions about what positively and negatively affect their occupational self-efficacy beliefs to continue working. First, data was analyzed using an inductive manifest qualitative content analysis. Next, descriptive statistics were performed based on the results of the qualitative study.

Results

The analyses revealed that health and working conditions that affect health were crucial facilitators and barriers for the aging engineers’ occupational self-efficacy to continue working until expected retirement age. Furthermore, the engineers emphasized competence, motivation from meaningful tasks, family and leisure, and private economy.

Discussion

The aging engineers’ own health seems to be prominent in their self-efficacy regarding a full working life; consequently, support still needs to address issues affecting health.
The problem with confidence: too much and too little results in poorer achievement, inner conflict, and social inhibition
Authors: Douglas Heather E. , Cunningham Mitchell L. , Tisdell Jessika , Arneson Justin
Published: May 2023

Introduction

Confidence is defined as the feelings and thoughts people have during a task that result in judgments about their performance. Evidence suggests that confidence is trait-like, but thus far research on the relative match between confidence and accuracy has been primarily restricted to over-confidence effects, and subject to the methodological flaws involved with using difference scores. We sought to answer an exploratory question in this research, whether discrepancies in ability and confidence in either direction reliably predicted individual differences on a broad-spectrum and commercially available personality test, the California Psychological Inventory (CPI260).

Methods

Participants were 220 employed adults who had previously taken the CPI260 for career development purposes. They were invited to complete a measure of cognitive ability and confidence in return for feedback on the same. Data were modeled using polynomial regression and response surface analysis, to determine whether and how CPI260 personality traits were associated with matches or mismatches between accuracy and confidence in the same test.

Results

We identified negative curvilinear effects along the line of disagreement for four CPI260 scales, suggesting that both under- and over-confidence were associated with personality.

Discussion

In contrast to our expectations, individuals who were under-confident and those who were over-confident had lower achievement potential, less social confidence, and more inner conflict than other individuals in this sample. Although preliminary, these findings suggest that both over-confident and under-confident individuals are aware of potential weaknesses that impede their functioning.
Infant exposure to Fluvoxamine through placenta and human milk: a case series - A contribution from the ConcePTION project
Authors: Monfort Anaëlle , Cardoso Evelina , Eap Chin B. , Fischer Fumeaux Céline J. , Graz Myriam Bickle , Morisod Harari Mathilde , Weisskopf Etienne , Gandia Peggy , Allegaert Karel , Nordeng Hedvig , Hascoët Jean-Michel , Claris Olivier , Epiney Manuella , Csajka Chantal , Guidi Monia , Ferreira Ema , Panchaud Alice
Published: May 2023

Introduction

Fluvoxamine is widely used to treat depression during pregnancy and lactation. However, limited data are available on its transfer to the fetus or in human milk. This case series provides additional information on the infant exposure to fluvoxamine during pregnancy and lactation.

Case presentation

Two women, aged 38 and 34 years, diagnosed with depression were treated with 50 mg fluvoxamine during pregnancy and lactation. At delivery a paired maternal and cord blood sample was collected for each woman. The first mother exclusively breastfed her child for 4 months and gave one foremilk and one hindmilk sample at 2 days and 4 weeks post-partum, whereas the second mother did not breastfeed.

Results

The cord to plasma concentration ratios were 0.62 and 0.48, respectively. At 2 weeks post-partum, relative infant doses (RID) were 0.47 and 0.57% based on fluvoxamine concentrations in foremilk and hindmilk, respectively. At 4 weeks post-partum, the RIDs were 0.35 and 0.90%, respectively. The child from the first mother was born healthy and showed a normal development at the 6th, 18th and 36th month follow-ups. One of the twins from the second woman was hospitalized for hypoglycemia that was attributed to gestational diabetes and low birth weight. The second one was born healthy.

Conclusion

These results suggest a minimal exposure to fluvoxamine during lactation which is in accordance with previously published data. Larger clinical and pharmacokinetic studies assessing the long-term safety of this drug during lactation and the variability of its exposure through breastmilk are warranted.