bluuebunny/crossref_metadata_2025 huggingface dataset:
Accuracy of automatic and manual dynamic navigation registration techniques for dental implant surgery in posterior sites missing a single tooth: A retrospective clinical analysis
Authors: Wu Bin‐Zhang , Xue Fei , Ma Yu , Sun Feng
Published: January 2023

Objectives

To assess the relative accuracy of manual (U‐shaped tube) and automatic (two‐in‐one) dynamic navigation registration techniques for implant surgery performed in posterior sites missing one tooth.

Materials and Methods

This study included 58 partially edentulous patients with 58 implants, including 31 and 27 in the manual and automatic groups. Deviations between the planned and actual implant placement were assessed.

Results

The angular deviation in the overall study cohort was 2.54 ± 1.21°, while the 3D deviations at the implant platform and apex were 0.90 ± 0.46 mm and 1.04 ± 0.47 mm, respectively. The respective angular deviations in the manual and automatic groups were 2.82 ± 1.17° and 2.21 ± 1.19° (p > .05), while platform deviations were 0.89 ± 0.48 mm and 0.91 ± 0.45 mm (p > .05), and apex deviations were 0.99 ± 0.48 mm and 1.11 ± 0.46 mm (p > .05). No significant differences in absolute buccolingual, mesiodistal, or apicocoronal deviations were detected between these groups at either level (p > .05) nor were did deviation distributions differ in the buccolingual, mesiodistal, or apicocoronal directions at the platform or apex levels (p > .05).

Conclusions

Manual and automatic dynamic navigation registration techniques can achieve excellent accuracy when placing implants in posterior sites missing a single tooth. The two‐in‐one automatic registration technique can reduce the amount of time and intraoperative steps necessary to complete the registration process relative to the manual U‐shaped tube registration technique. Further follow‐up studies are necessary to expand on these results.
Artemisinin exerts a protective effect in the MPTP mouse model of Parkinson's disease by inhibiting microglial activation via the TLR4/Myd88/NF‐KB pathway
Authors: Lv Jing , Zhu Jing , Wang Peihan , Liu Tongyu , Yuan Jiang , Yin Huan , Lan Yiran , Sun Qiang , Zhang Zhifeng , Ding Guoda , Zhou Chenxi , Wang Huajie , Wang Zihan , Wang Yunfu
Published: January 2023

Aims

We performed cell and animal experiments to explore the therapeutic effect of artemisinin on Parkinson's disease (PD) and the TLR4/Myd88 signaling pathway.

Methods

C57 mice were randomly divided into the blank, 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐induced and artemisinin‐treated groups. Clinical symptoms, the number of dopaminergic (DAergic) neurons in the substantia nigra, and microglial cell activation were compared among the three groups. Subsequently, BV‐2 cell activation and TLR4/Myd88 pathway component expression were compared among the blank, MPP+‐treated, artemisinin‐treated, and TLR4 activator‐treated groups.

Results

Behavioral symptoms were improved, the number of DAergic neurons in the substantia nigra of the midbrain was increased, and microglial cell activation was decreased in artemisinin‐treated MPTP‐induced PD model mice compared with control‐treated MPTP‐induced PD model mice (p < 0.05). The cell experiments revealed that artemisinin treatment reduced MPP+‐induced BV‐2 cell activation and inhibited the TLR4/Myd88 signaling pathway. Moreover, the effect of artemisinin on the BV‐2 cell model was inhibited by the TLR4 activator LPS (p < 0.05).

Conclusion

Artemisinin may reduce damage to DAergic neurons in a PD mouse model by decreasing microglial activation through the TLR4‐mediated MyD88‐dependent signaling pathway. However, this finding cannot explain the relationship between microglia and DAergic neurons.
A gospel of irresolution: Illness, trauma, and getting to hope
Authors: Thompson Deanna A.
Published: January 2023

Our tellings of the Christian story often bend toward resolution while the plots of so many of our lives stubbornly resist it. If theologies and religious communities that embody them are going to be places where those who live with serious illness are able to held and supported in ways that mitigate some of their suffering, they need to be spacious enough to hold the grief, trauma, and temptations to despair that accompany those who are seriously ill. One way to do this is to take on the central Christian plotline—the one about death being transformed into new life, the one that bends toward resolution—and let it breathe. This essay begins with one story of what it is like to be undone by cancer, highlighting ways in which the lens of trauma helps illumine the depths of the challenges faced by those who are seriously ill. It then proposes how a gospel of irresolution can be good news to those undone by illness and other awfulness.
Identification of signalling downstream of the transcription factor forkhead box protein M1 that protects against endoplasmic reticulum stress in a diabetic foot ulcer model
Authors: Peng Weixia , Zhu Ting , Xiang Guangda , Ding Ting , Zhao Jun , Xiong Dan , Zhong Yaqin , Zhang Youqi
Published: January 2023

Aims

Diabetic foot ulcer (DFU) has a significant impact on the quality of life of diabetic mellitus (DM) patients. Here, we aimed to explore the molecules with aberrant expression and their regulatory mechanisms in DFU.

Methods

The expression of gene and protein was examined using quantitative polymerase chain reaction (qPCR) and western blot. Pearson's correlation analysis was used to analyse interactions among FOXM1, GAS5 and SDF4. Immunofluorescence was used to detect PDI and GRP78 expression. Flow cytometry was used to assess cell apoptosis. Tube formation assay was used to determine angiogenic capacity. Fluorescence in situ hybridization (FISH) assay was employed to determine the cellular localization of GAS5 and SDF4 in human umbilical vein endothelial cells (HUVECs). The interactions among FOXM1, GAS5 and SDF4 were validated by chromatin immunoprecipitation (ChIP), luciferase, RNA pull‐down and RNA immunoprecipitation (RIP) assays.

Results

FOXM1, GAS5 and SDF4 were decreased in the skin tissues of DFU patients. High glucose (HG) stimulation induced endoplasmic reticulum (ER) stress and cell apoptosis but suppressed angiogenesis in HUVECs, which were abolished by FOXM1 overexpression. FOXM1 promoted GAS5 transcriptional activity, resulting in increased GAS5 expression, and GAS5 knockdown reversed the effects of FOXM1 overexpression in HG‐treated HUVECs. Moreover, GAS5 recruited TAF15 to promote SDF4 expression in HUVECs. GAS5 overexpression inhibited ER stress, cell apoptosis and induced angiogenesis in HG‐treated HUVECs which could be reversed by silencing SDF4.

Conclusion

Our results revealed that FOXM1 suppressed ER stress, cell apoptosis and promoted angiogenesis in HG‐induced HUVECs via mediating GAS5/TAF15/SDF4 axis, providing a novel therapeutic molecule mechanism for DFU.
Multisite validation of a host response signature for predicting likelihood of bacterial and viral infections in patients with suspected influenza
Authors: Shojaei Maryam , Chen Uan‐I , Midic Uros , Thair Simone , Teoh Sally , McLean Anthony , Sweeney Timothy E. , Thompson Matthew , Liesenfeld Oliver , Khatri Purvesh , Tang Benjamin
Published: January 2023

Background

Indiscriminate use of antimicrobials and antimicrobial resistance is a public health threat. IMX‐BVN‐1, a 29‐host mRNA classifier, provides two separate scores that predict likelihoods of bacterial and viral infections in patients with suspected acute infections. We validated the performance of IMX‐BVN‐1 in adults attending acute health care settings with suspected influenza.

Method

We amplified 29‐host response genes in RNA extracted from blood by NanoString nCounter. IMX‐BVN‐1 calculated two scores to predict probabilities of bacterial and viral infections. Results were compared against the infection status (no infection; highly probable/possible infection; confirmed infection) determined by clinical adjudication.

Results

Amongst 602 adult patients (74.9% ED, 16.9% ICU, 8.1% outpatients), 7.6% showed in‐hospital mortality and 15.5% immunosuppression. Median IMX‐BVN‐1 bacterial and viral scores were higher in patients with confirmed bacterial (0.27) and viral (0.62) infections than in those without bacterial (0.08) or viral (0.21) infection, respectively. The AUROC distinguishing bacterial from nonbacterial illness was 0.81 and 0.87 when distinguishing viral from nonviral illness. The bacterial top quartile's positive likelihood ratio (LR) was 4.38 with a rule‐in specificity of 88%; the bacterial bottom quartile's negative LR was 0.13 with a rule‐out sensitivity of 96%. Similarly, the viral top quartile showed an infinite LR with rule‐in specificity of 100%; the viral bottom quartile had a LR of 0.22 and a rule‐out sensitivity of 85%.

Conclusion

IMX‐BVN‐1 showed high accuracy for differentiating bacterial and viral infections from noninfectious illness in patients with suspected influenza. Clinical utility of IMX‐BVN will be validated following integration into a point of care system.
Using computer vision to understand the global biogeography of ant color
Authors: Idec Jacob H. , Bishop Tom R. , Fisher Brian L.
Published: January 2023

Organisms use color to serve a variety of biological functions, including camouflage, mate attraction and thermoregulation. The potential adaptive role of color is often investigated by examining patterns of variation across geographic, habitat and life‐history gradients. This approach, however, presents a data collection trade‐off whereby researchers must either maximize intraspecific detail or taxonomic and geographic coverage. This limits our ability to fully understand color variation across entire taxonomic groups at global scales. We provide a solution by extracting color data from more than 44 000 individual specimens of ants, representing over 14 000 species and morphospecies, using a computer vision algorithm on ant head images. Our analyses on this dataset reveal that ants are dominated by variation in the dark‐pale color spectrum, that much of this variation is held within species, and that, overall, a suite of popular ecogeographic hypotheses are unable to explain intra‐ and interspecific variation in ant color. This is in contrast to previous work at the assemblage level in ants and other invertebrates demonstrating clear and strong links between variables such as temperature and the average color of entire assemblages. Our work applies a novel computational approach to the study of large‐scale trait diversity. By doing so, we reveal previously unknown levels of intraspecific variation. Similar approaches may unlock a vast amount of data residing in museum and specimen databases and establish a digital platform for a data collection revolution in functional biogeography.
Clinical activities suspended: How the COVID‐19 affected the self‐confidence of Italian dental students
Authors: Francesca Zotti , Luca Rosolin , Andrea Poscolere , Davide Pappalardo , Nicoletta Zerman
Published: January 2023

Introduction

COVID‐19 emergency caused several effects on the dental educational system, especially affecting courses including practical activities. The study aims to evaluate the impact of the suspension of dental clinical activities on the Italian dental students' self‐confidence. Furthermore, the other purpose of the research is to find an integrative didactics solution to improve the clinical training of dentistry during the COVID‐19 pandemic.

Materials and Methods

A questionnaire was administered to evaluate the impact of the suspension of clinical activities on dental students' self‐confidence. A 67‐questions survey tested the students' self‐confidence in several dental disciplines (Conservative Dentistry, Endodontics, Oral Surgery and Dental Emergency). The study reached a sample of 193 dental students and the answers from 9 different Italian dental schools were analysed.

Results

The degree of students' self‐confidence for all the dental disciplines investigated was found statistically different between the periods before and after the interruption of clinical activities. The students proposed, as a potential solution to improve their practice during the COVID‐19 pandemic, to combinate the use of a video tutorials and dental simulators.

Conclusion

The interruption of the training in clinical practice significantly affected the educational career and the self‐confidence of students. An alternative teaching method involving the use of video tutorials as support in teaching clinical procedures deserves to be considered.
Severity of in vivo corticospinal tract degeneration is associated with survival in amyotrophic lateral sclerosis: a longitudinal, multicohort study
Authors: Ta Daniel , Ishaque Abdullah H. , Elamy Adam , Anand Tanushka , Wu Andrew , Eurich Dean T. , Luk Collin , Yang Yee Hong , Kalra Sanjay
Published: January 2023

Background and purpose

This study sought to evaluate the relationship of progressive corticospinal tract (CST) degeneration with survival in patients with amyotrophic lateral sclerosis (ALS).

Methods

Forty‐one ALS patients and 42 healthy controls were prospectively recruited from the Canadian ALS Neuroimaging Consortium. Magnetic resonance imaging scanning and clinical evaluations were performed on participants at three serial visits with 4‐month intervals. Texture analysis was performed on T1‐weighted magnetic resonance imaging scans and the texture feature ‘autocorrelation’ was quantified. Whole‐brain group‐level comparisons were performed between patient subgroups. Linear mixed models were used to evaluate longitudinal progression. Region‐of‐interest and 3D voxel‐wise Cox proportional‐hazards regression models were constructed for survival prediction. For all survival analyses, a second independent cohort was used for model validation.

Results

Autocorrelation of the bilateral CST was increased at baseline and progressively increased over time at a faster rate in ALS short survivors. Cox proportional‐hazards regression analyses revealed autocorrelation of the CST as a significant predictor of survival at 5 years follow‐up (hazard ratio 1.28, p = 0.005). Similarly, voxel‐wise whole‐brain survival analyses revealed that increased autocorrelation of the CST was associated with shorter survival. ALS patients stratified by median autocorrelation in the CST had significantly different survival times using the Kaplan–Meier curve and log‐rank tests (χ2 = 7.402, p = 0.007).

Conclusions

Severity of cerebral degeneration is associated with survival in ALS. CST degeneration progresses faster in subgroups of patients with shorter survival. Neuroimaging holds promise as a tool to improve patient management and facilitation of clinical trials.
Long‐term favorable prognosis in late onset dominant distal titinopathy: Tibial muscular dystrophy
Authors: Lillback Victoria , Savarese Marco , Sandholm Niina , Hackman Peter , Udd Bjarne
Published: January 2023

Background and purpose

Tibial muscular dystrophy (TMD) is a dominant late onset distal titinopathy. It was first described in Finnish patients 3 decades ago. TMD patients with several other TTN mutations occur in many European populations. In this retrospective study, we were able to obtain longitudinal follow‐up data of the disease progression over 15 years in 137 TMD patients.

Methods

We retrieved clinical data retrospectively from three examinations spanning a period of 15 years. The data were analyzed in R. Frequencies, percentages, and median values were used to describe data. Probability values were determined with the chi‐squared test.

Results

In the cohort, the first symptoms were walking difficulties (97.8%) and weakness in distal lower limbs (98.5%). The progression of the weakness in distal lower limbs was moderate, and in the proximal lower limbs and proximal upper limbs it was mild. The distal upper limbs were not affected. Magnetic resonance imaging results indicated fatty degeneration preferentially in lower leg anterior muscles, gluteus minimus, and hamstring muscles. Serum creatine kinase values in the cohort were mostly normal (40.7%) or mildly elevated (53.7%). The data suggest that 50% of patients need walking aids by the age of 88 years.

Conclusions

Despite individual variability of severity, the overall disability due to walking difficulties and upper limb weakness remained moderate even at very advanced ages, and cardiomyopathy did not develop due to the titin defect alone. The acquired results promote the correct identification of TMD, and the obtained trajectories of disease evolution can be used as natural history data for any therapeutic intervention.
Interplay between the catecholaminergic enzymatic axis and neurodegeneration/neuroinflammation processes in the Alzheimer's disease continuum
Authors: Motta Caterina , Assogna Martina , Bonomi Chiara Giuseppina , Di Lorenzo Francesco , Nuccetelli Marzia , Mercuri Nicola Biagio , Koch Giacomo , Martorana Alessandro
Published: January 2023

Background and Purpose

The locus coeruleus (LC) provides dopamine/noradrenaline (DA/NA) innervation throughout the brain and undergoes early degeneration in Alzheimer's disease (AD). We evaluated catecholaminergic enzyme levels in the cerebrospinal fluid (CSF) of a group of patients biologically defined as within the AD continuum (ADc) and explored their relationship with AD biomarkers and cytokine/growth factor levels to investigate their interplay with neurodegenerative and neuroinflammatory processes.

Methods

The CSF concentration of DA transporter (DAT), tyrosine‐hydroxylase (TH), DOPA‐decarboxylase (DDC), and dopamine‐β‐hydroxylase (DβH), as well as cytokine/growth factor levels, were analyzed in 41 ADc patients stratified according to CSF beta‐amyloid (Aβ)1‐42 (A) and p‐tau (T) in AD pathological changes (A+ T‐) and AD (A+ T+) subgroups, as well as in 15 control subjects (A‐ T‐).

Results

The ADc group had lower CSF levels of DAT and TH but increased DβH levels to compensate for NA synthesis. DDC levels were higher in the A+ T+ subgroup but comparable with controls in the A+ T– subgroup, probably because the DA system is resilient to the degeneration of LC neurons in the absence of tau pathology. Adjusting for age, sex, APOE genotype, and cognitive status, a significant association was found between TH and Aβ1‐42 (R2 = 0.25) and between DDC and p‐tau (R2 = 0.33). Finally, TH correlated with interleukin (IL)‐10 levels (p = 0.0008) and DβH with IL‐1β (p = 0.03), IL‐4 (p = 0.02), granulocyte colony‐stimulating factor (p = 0.007), and IL‐17 (p = 0.01).

Conclusions

Taken together, these findings suggest that catecholaminergic enzymes, functional markers of the catecholaminergic system, are closely linked to the neurodegenerative and neuroinflammatory processes in AD pathology.
Chronic inflammatory demyelinating polyradiculoneuropathy‐associated tremor: Phenotype and pathogenesis
Authors: Silsby Matthew , Fois Alessandro F. , Yiannikas Con , Ng Karl , Kiernan Matthew C. , Fung Victor S. C. , Vucic Steve
Published: January 2023

Background and purpose

Tremor in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is underrecognized, and the pathophysiology remains incompletely understood. This study evaluated tremor in CIDP and tested the hypothesis, established in other demyelinating neuropathies, that tremor occurs due to mistimed peripheral inputs affecting central motor processing. Additionally, the tremor stability index (TSI) was calculated with the hypothesis that CIDP‐related tremor is more variable than other tremor disorders.

Methods

Consecutive patients with typical CIDP were prospectively recruited from neuromuscular clinics. Alternative causes of neuropathy and tremor were excluded. Cross‐sectional clinical assessment and extensive tremor study recordings were undertaken. Pearson correlation coefficient was used to compare nerve conduction studies and tremor characteristics, and t‐test was used for comparisons between groups.

Results

Twenty‐four patients with CIDP were included. Upper limb postural and action tremor was present in 66% and was mild according to the Essential Tremor Rating Assessment Scale. Tremor did not significantly impact disability. Surface electromyography (EMG) found high‐frequency spectral peaks in deltoid (13.73 ± 0.66 Hz), biceps brachii (11.82 ± 0.91 Hz), and extensor carpi radialis (11.87 ± 0.91 Hz) muscles, with lower peaks in abductor pollicis brevis EMG (6.07 ± 0.45 Hz) and index finger accelerometry (6.53 ± 0.42 Hz). Tremor was unchanged by weight loading but correlated with ulnar nerve F‐wave latency and median nerve sensory amplitude. TSI (2.3 ± 0.1) was significantly higher than essential tremor.

Conclusions

Postural tremor is a common feature in CIDP. Tremor was unaffected by weight loading, typical of centrally generated tremors, although there was a correlation with peripheral nerve abnormalities. The high beat‐to‐beat variability on TSI and gradation of peak frequencies further suggest a complex pathophysiology. These findings may assist clinicians with the diagnosis of neuropathic tremor.
Endovascular thrombectomy for basilar artery occlusion stroke: Analysis of the German Stroke Registry‐Endovascular Treatment
Authors: Feil Katharina , Berndt Maria Teresa , Wunderlich Silke , Maegerlein Christian , Bernkopf Kathleen , Zimmermann Hanna , Herzberg Moriz , Tiedt Steffen , Küpper Clemens , Wischmann Johannes , Schönecker Sonja , Dimitriadis Konstantin , Liebig Thomas , Dieterich Marianne , Zimmer Claus , Kellert Lars , Boeckh‐Behrens Tobias ,   for the GSR Investigators
Published: January 2023

Background and purpose

Acute ischemic stroke due to basilar artery occlusion (BAO) causes the most severe strokes and has a poor prognosis. Data regarding efficacy of endovascular thrombectomy in BAO are sparse. Therefore, in this study, we performed an analysis of the therapy of patients with BAO in routine clinical practice.

Methods

Patients enrolled between June 2015 and December 2019 in the German Stroke Registry‐Endovascular Treatment (GSR‐ET) were analyzed. Primary outcomes were successful reperfusion (modified Thrombolysis in Cerebral Infarction [mTICI] score of 2b‐3), substantial neurological improvement (≥8‐point National Institute of Health Stroke Scale [NIHSS] score reduction from admission to discharge or NIHSS score at discharge ≤1), and good functional outcome at 3 months (modified Rankin Scale [mRS] score of 0–2).

Results

Out of 6635 GSR‐ET patients, 640 (9.6%) patients (age 72.2 ± 13.3, 43.3% female) experienced BAO (median [interquartile range] NIHSS score 17 [8, 27]). Successful reperfusion was achieved in 88.4%. Substantial neurological improvement at discharge was reached by 45.5%. At 3‐month follow‐up, good clinical outcome was observed in 31.1% of patients and the mortality rate was 39.2%. Analysis of mTICI3 versus mTICI2b groups showed considerable better outcome in those with mTICI3 (38.9% vs. 24.4%; p = 0.005). The strongest predictors of good functional outcome were intravenous thrombolysis (IVT) treatment (odds ratio [OR] 3.04, 95% confidence interval [CI] 1.76–5.23) and successful reperfusion (OR 4.92, 95% CI 1.15–21.11), while the effect of time between symptom onset and reperfusion seemed to be small.

Conclusions

Acute reperfusion strategies in BAO are common in daily practice and can achieve good rates of successful reperfusion, neurological improvement and good functional outcome. Our data suggest that, in addition to IVT treatment, successful and, in particular, complete reperfusion (mTICI3) strongly predicts good outcome, while time from symptom onset seemed to have a lower impact.
Risk of poststroke epilepsy after reperfusion therapies: A national cohort study
Authors: Eriksson Hanna , Nordanstig Annika , Rentzos Alexandros , Zelano Johan , Redfors Petra
Published: January 2023

Background and purpose

The risk of poststroke epilepsy (PSE) after endovascular treatment (EVT) is not well characterized. In this nationwide study, we assessed the risk of PSE after EVT and identified associated predictors.

Methods

We included all individuals (n = 3319) treated with EVT (±intravenous thrombolysis [IVT]) between 2015 and 2019 in the Swedish National Quality Register for EVT. Two control groups were identified from the Swedish Stroke Register: the first treated with IVT alone (n = 3132) and the second with no treatment (n = 3184), both matched for age, sex, stroke severity, and time of stroke.

Results

PSE developed in 7.9% (n = 410). The survival‐adjusted 2‐year risk was 6.5% (95% confidence interval [CI] = 5.28–7.70) after EVT, 10.0% (95% CI = 8.25–11.75) after IVT, and 12.3% after no revascularization (95% CI = 10.33–14.25). The hazard ratio (HR) of PSE after EVT was almost half compared to no treatment (HR = 0.51, 95% CI = 0.41–0.64). The risk of PSE after EVT was lower compared to no treatment in a multivariable Cox model that adjusted for age, sex, hemicraniectomy, and stroke severity (HR = 0.76, 95% CI = 0.60–0.96). Multivariable predictors of PSE after EVT were large infarction on computed tomography Day 1, high posttreatment National Institutes of Health Stroke Scale score, and need of assistance 3 months after stroke. IVT before EVT was associated with a lower risk of PSE (HR = 0.66, 95% CI = 0.46–0.94).

Conclusions

This nationwide study identified a reduced risk of PSE after EVT. Markers of severe infarction after EVT were associated with PSE, whereas IVT given before EVT was protective.
Cortical lesions at diagnosis predict long‐term cognitive impairment in multiple sclerosis: A 20‐year study
Authors: Ziccardi Stefano , Pisani Anna Isabella , Schiavi Gian Marco , Guandalini Maddalena , Crescenzo Francesco , Colombi Annalisa , Peloso Angela , Tamanti Agnese , Bertolazzo Maddalena , Marastoni Damiano , Calabrese Massimiliano
Published: January 2023

Background and purpose

Although cognitive impairment (CI) is frequent in multiple sclerosis (MS) patients, few studies (and with conflicting results) have evaluated early predictors of CI in the long term. We aimed at determining associations between early clinical/neuroradiological variables with reference to CI after 20 years of MS.

Methods

We investigated in 170 MS patients the relationship between clinical/magnetic resonance imaging (MRI) data at diagnosis and cognitive status almost 20 years after MS onset. Among others, number and volume of both white matter lesions (WMLs) and cortical lesions (CLs) were evaluated at diagnosis and after 2 years. All MS patients were followed over time and underwent a comprehensive neuropsychological assessment at the end of study. Advanced statistical methods (unsupervised cluster analysis and random forest model) were conducted.

Results

CI patients showed higher focal cortical pathology at diagnosis compared to cognitively normal subjects (p < 0.001). Volumes of both WMLs and CLs emerged as the MRI metrics most associated with long‐term CI. Moreover, number of CLs (especially ≥3) was also strongly associated with long‐term CI (≥3 CLs: odds ratio [OR] = 3.7, 95% confidence interval = 1.8–7.5, p < 0.001), more than number of WMLs; the optimal cutoff of three CLs (area under the curve = 0.67, specificity = 75%, sensitivity = 55%) was estimated according to the risk of developing CI.

Conclusions

These results highlight the impact of considering both white and gray matter focal damage from early MS stages. Given the low predictive value of WML number and the poor clinical applicability of lesion volume estimation in the daily clinical context, the evaluation of number of CLs could represent a reliable prognostic marker of CI.
Genotype–phenotype characteristics and baseline natural history of Chinese myelin protein zero gene related neuropathy patients
Authors: Lei Liu , Xiaobo Li , Zhiqiang Lin , Yongzhi Xie , Shunxiang Huang , Huadong Zhao , Beisha Tang , Ruxu Zhang
Published: January 2023

Background and purpose

The aim was to characterize the phenotypic and genotypic features of myelin protein zero (MPZ) related neuropathy and provide baseline data for longitudinal natural history studies or drug clinical trials.

Method

Clinical, neurophysiological and genetic data of 37 neuropathy patients with MPZ mutations were retrospectively collected.

Results

Nineteen different MPZ mutations in 23 unrelated neuropathy families were detected, and the frequency of MPZ mutations was 5.84% in total. Mutations c.103_104InsTGGTTTACACCG, c.513dupG, c.521_557del and c.696_699delCAGT had not been reported previously. Hot spot mutation p.Thr124Met was detected in four unrelated families, and seven patients carried de novo mutations. The onset age indicated a bimodal distribution: prominent clustering in the first and fourth decades. The infantile‐onset group included 12 families, the childhood‐onset group consisted of two families and the adult‐onset group included nine families. The Charcot–Marie–Tooth Disease Neuropathy Score ranged from 3 to 25 with a mean value of 15.85 ± 5.88. Mutations that changed the cysteine residue (p.Arg98Cys, p.Cys127Trp, p.Ser140Cys and p.Cys127Arg) in the extracellular region were more likely to cause severe early‐onset Charcot–Marie–Tooth disease type 1B (CMT1B) or Dejerine–Sottas syndrome. Nonsense‐mediated mRNA decay mutations p.Asp35delInsVVYTD, p.Leu174Argfs*66 and p.Leu172Alafs*63 were related to severe infantile‐onset CMT1B or Dejerine–Sottas syndrome; however, mutation p.Val232Valfs*19 was associated with a relatively milder childhood‐onset CMT1 phenotype.

Conclusion

Four novel MPZ mutations are reported that expand the genetic spectrum. De novo mutations accounted for 30.4% and were most related to a severe infantile‐onset phenotype. Genetic and clinical data from this cohort will provide the baseline data necessary for clinical trials and natural history studies.
Performance validity tests in nonlitigant patients with functional motor disorder
Authors: Di Vico Ilaria A. , Stone Jon , Mcwhirter Laura , Riello Marianna , Zanolin Maria Elisabetta , Colombari Michela , Fiorio Mirta , Tinazzi Michele
Published: January 2023

Background and purpose

Performance validity tests (PVTs) are used in neuropsychological assessments to detect patterns of performance suggesting that the broader evaluation may be an invalid reflection of an individual's abilities. Data on functional motor disorder (FMD) are currently poor and conflicting. We aimed to examine the rate of failure on three different PVTs of nonlitigant, non‐compensation‐seeking FMD patients, and we compared their performance to that of healthy controls and controls asked to simulate malingering (healthy simulators).

Methods

We enrolled 29 nonlitigant, non‐compensation‐seeking patients with a clinical diagnosis of FMD, 29 healthy controls, and 29 healthy simulators. Three PVTs, the Coin in the Hand Test (CIH), the Rey 15‐Item Test (REY), and the Finger Tapping Test (FTT), were employed.

Results

Functional motor disorder patients showed low rates of failure on the CIH and REY (7% and 10%, respectively) and slightly higher rates on the FTT (15%, n = 26), which implies a motor task. Their performance was statistically comparable to that of healthy controls but statistically different from that of healthy simulators (p < 0.001). Ninety‐three percent of FMD patients, 7% of healthy simulators, and 100% of healthy controls passed at least two of the three tests.

Conclusions

Performance validity test performance of nonlitigant, non‐compensation‐seeking patients with FMD ranged from 7% to 15%. Patients' performance was comparable to that of controls and significantly differed from that of simulators. This simple battery of three PVTs could be of practical utility and routinely used in clinical practice.
Virulence evolution of Toxoplasma gondii within a multi‐host system
Authors: Wang Mengyue , Jiang Wen
Published: January 2023

Current research on the virulence evolution of Toxoplasma gondii is mainly conducted via experiments, and studies using mathematical models are still limited. Here, we constructed a complex cycle model of T. gondii in a multi‐host system considering multiple transmission routes and cat‐mouse interaction. Based on this model, we studied how the virulence of T. gondii evolves with the factors related to transmission routes and the regulation of infection on host behavior under an adaptive dynamics framework. The study shows that all factors that enhance the role of mice favored decreased virulence of T. gondii, except the decay rate of oocysts that led to different evolutionary trajectories under different vertical transmission. The same was true of the environmental infection rate of cats, whose effect was different under different vertical transmission. The effect of the regulation factor on the virulence evolution of T. gondii was the same as that of the inherent predation rate depending on its net effect on direct and vertical transmissions. The global sensitivity analysis on the evolutionary outcome suggests that changing the vertical infection rate and decay rate was most effective in regulating the virulence of T. gondii. Furthermore, the presence of coinfection would favor virulent T. gondii and make evolutionary bifurcation easy to occur. The results reveal that the virulence evolution of T. gondii had a compromise between adapting to different transmission routes and maintaining the cat‐mouse interaction thereby leading to different evolutionary scenarios. This highlights the significance of evolutionary ecological feedback to evolution. In addition, the qualitative verification of T. gondii virulence evolution in different areas by the present framework will provide a new perspective for the study of evolution.
Efficacy and safety of topical JAK inhibitors in the treatment of atopic dermatitis in paediatrics and adults: A systematic review
Authors: Sadeghi Sara , Mohandesi Nessa Aghazadeh
Published: January 2023

Atopic dermatitis (AD) is the most common skin inflammatory disease. Dysregulation of innate and adaptive immune systems plays a major role in the pathophysiology of AD. JAKi (Janus Kinase Inhibitors) reduce the production of pro‐inflammatory cytokines and represent a promising novel treatment for AD. To assess and summarize the overall efficacy and safety of topial JAKi in the treatment of AD in adults and pediatrics, a broad search was performed on Ovid Medline, Ovid Embase, Cochrane Library, Web of Sciences, Scopus, CINAHL and Google Scholar until 14 June 2022. After screening, 19 studies remained for the final review. The current systematic review was conducted according to PRISMA, and the protocol was registered in PROSPERO (ID #CRD42022303321). Topical delgocitinib, tofacitinib, ruxolitinib, cerdulatinib and ifidancitinib are effective in treating AD and significantly improve EASI, IGA, pruritus‐NRS score and some other indexes in adults. Moreover, topical delgocitinib was observed to have a great efficacy in the treatment of AD in paediatrics. All topical JAKi showed minimal risk of mild‐to‐moderate adverse effects. Available topical JAKi are effective and safe modalities in treating AD. Nevertheless, further studies with longer duration and head‐to‐head comparative trials are necessary to find the best option with the least adverse effects.
Inhibition of eukaryotic initiation factor 4E by tomivosertib suppresses angiogenesis, growth, and survival of glioblastoma and enhances chemotherapy's efficacy
Authors: Zhang Qi , Zhao Juan , Xu Tingwei
Published: January 2023

Glioblastoma is characterized by extensive vascularization and is highly resistant to current therapy. Identification of drugs that target tumor directly and angiogenesis processes present an effective therapeutic strategy for glioblastoma. Mnk kinase is required for the activation of eukaryotic initiation factor 4E (eIF4E), which mediates translation of oncogenic proteins. We investigated the effects of tomivosertib, a novel MAPK‐interacting kinase (MNK) inhibitor, on glioblastoma angiogenesis, growth, and survival. We found that tomivosertib inhibited growth and induced caspase‐dependent apoptosis in various glioblastoma cell lines. Tomivosertib disrupted glioblastoma endothelial cell capillary network formation, growth, and survival. Mechanistically, tomivosertib acted on glioblastoma via suppressing MNK‐dependent eIF4E phosphorylation and activation in tumor and endothelial cells. We further found that temozolomide activated eIF4E and this was reversed by tomivosertib. Using glioblastoma xenograft mouse model, we demonstrated that temozolomide and tomivosertib combination had higher efficacy than tomivosertib alone. Of note, tomivosertib inhibited glioblastoma angiogenesis and decreased p‐eIF4E level in mice. We finally showed that p‐eIF4E activation was a common molecular feature in glioblastoma patients. Our pre‐clinical findings suggest that tomivosertib is a useful addition to the treatment armamentarium for glioblastoma and that targeting MNK‐eIF4E pathway represents a therapeutic strategy to overcome glioblastoma chemoresistance.
Trait–environment relationships of hydroids (Cnidaria: Hydrozoa) across large spatial and environmental gradients in the Atlantic Ocean
Authors: Fernandez Marina Oliveira , Jaimes‐Becerra Adrian , Marques Antonio Carlos
Published: January 2023

Aim

The aim was to test trait–environment relationships in hydroids across large spatial and environmental gradients and to evaluate associations between traits, environmental variables, space and phylogeny.

Location

Atlantic Ocean and adjacent polar seas.

Time period

Present day.

Major taxa studied

Hydrozoa.

Methods

Trait–environment relationships and their spatial and phylogenetic contexts were assessed in hydroids by using a combination of a fourth‐corner test and extended‐RLQ approach, in a multivariate ordination method that uses five matrices: (1) species across sites, (2) environmental data across sites, (3) traits across species, (4) latitude and longitude for each site, and (5) phylogenetic distance among species. We based our analyses on 3680 records of 431 species distributed at 1440 sites, 16 species traits, nine environmental variables and a phylogenetic tree of the studied species.

Results

Hydroid traits are significantly correlated with environmental variables and geographical space, and hydroid phylogeny is correlated with the environment and geographical space. More evidently, we observed an increased presence of larger species (taller, more branched, with greater base diameter and polysiphonic) at sites richer in nitrate and silicate, with higher dissolved oxygen, lower temperatures, lower salinities and lower current velocities. The observation of phylogenetically related species with similar traits and distributions corroborates that historical processes interact with the environment in determining community assembly and explaining patterns of distribution of species traits.

Main conclusions

Several environmental variables combined affect the distribution of hydroid traits, which are also influenced by spatial and historical factors. In the first analysis of its kind for hydrozoans, we have provided an overview of how hydroids are distributed across environments according to their traits and revealed the spatial and phylogenetic components of these trait–environment relationships.
Apoptosis versus necrosis in tubal ectopic pregnancies following Methotrexate
Authors: Gil Yaron , Zubkov Asia , Balayla Jacques , Cohen Aviad , Levin Ishai
Published: January 2023

Methotrexate administration for the treatment of tubal ectopic pregnancies has been shown to cause tubal mass enlargement. Our hypothesis was that, by administrating Methotrexate, a local necrotic reaction occurs, leading to hematoma formation and eventually fallopian tube rupture. Salpingectomy specimens were collected, analysed and divided into three equal groups: patients who received Methotrexate but who ultimately failed medical treatment, patients who had a viable ectopic pregnancy and patients with a self‐resolving ectopic pregnancy that were operated due to other medical indications. The specimens were dyed using the Cleaved Caspase‐3 (Asp175) Rabbit mA. Specimens were divided into three equal groups and analysed. The patients in self‐resolving ectopic pregnancy group were older and had more pregnancies. Rates of apoptosis were found to be less than 1% per slide. Necrosis was not evident in any of the pathological specimens. It seems Methotrexate administration does not lead to a significant tubal necrotic reaction. Further studies are required.
Family and work‐related risk factors in children's social–emotional well‐being and parent–educator cooperation in flexibly scheduled early childhood education and care
Authors: Koivula Merja , Räikkönen Eija , Turja Leena , Poikonen Pirjo‐Liisa , Laakso Marja‐Leena
Published: January 2023

Non‐standard work schedules (NSWS) have become typical, but their associations with childcare arrangements and children's well‐being are unknown. This study explores how risk factors are associated with the social–emotional well‐being of girls and boys using flexibly scheduled early childhood education and care. Furthermore, the study investigates whether well‐functioning cooperation between parents and educators buffers the negative effects of the risk factors. This study, which is a part of a larger survey carried out in three European countries, reports Finnish parents' (N = 146) perspectives. The results showed that high parental stress was associated with low child well‐being. Strong parent–educator cooperation positively impacted both boys' and girls' social–emotional well‐being. The risk factors of reconciling work and family life had negative associations with children's well‐being and the fulfilment of their basic needs. The results illustrate the complex interrelations between children's well‐being, risk factors relating to NSWS and the buffering effect of protective factors.
Pleistocene megafaunal extinction in the grasslands of Junín‐Peru
Authors: Rozas‐Davila Angela , Rodbell Donald T. , Bush Mark B.
Published: January 2023

Aim

To determine the timing of megafaunal extinction in the high plains of Peru and also to determine if the timing was delayed in grasslands compared with previously published forested settings to dissociate the effects of succession from human or climatic impacts.

Location

The Junín Plateau, Peru.

Taxon

Flowering plants and Ascomycetes.

Methods

The sediments used in this analysis were collected from the edge of Lake Junín, Peru. Eleven ages derived from 14C accelerator mass spectrometry provide a chronology. We provide a paleoecological reconstruction of past climate and vegetation change, fire history and megafaunal herbivore presence from c. 20,000–7000 years ago based on fossil pollen, charcoal and Sporormiella spores. Data were analysed using multivariate analysis and Bayesian change point analysis.

Results

Megafaunal populations appear to have been positively impacted by dry climatic oscillations until c. 15,200 years ago. A reduction in Sporormiella abundance between 13,000 and 12,300 years before the present coincides with increased charcoal abundance and is identified as the period of megafaunal population collapse leading to extinction. The timing of the extinction does not differ substantially from that observed in wooded Andean settings.

Main Conclusion

The timing of the collapse of megafaunal populations in high grasslands was very similar to that of lower, now‐forested settings. Upticks in fire activity, during what is generally seen to be a wet period, formed the backdrop to extinction and are strongly associated with human activity.
Comparing dominance relationships and movement of native marble trout (Salmo marmoratus) and introduced rainbow trout (Oncorhynchus mykiss)
Authors: Pengal Polona , Cokan Blaž , Økland Finn , Höjesjö Johan , Tambets Meelis , Thorstad Eva Bonsak
Published: January 2023

Behaviour observations of the endangered native marble trout (Salmo marmoratus, Cuvier, 1829) and introduced rainbow trout (Oncorhynchus mykiss, Walbaum, 1792) in the laboratory and in a tributary to the Idrijca River in Slovenia were combined to study the movements and dominance relationships between individuals of the two species in an open field test. Under laboratory conditions, no difference between the species was detected for neither time spent actively or distance moved. In species paired tests, rainbow trout initiated more aggressive behaviours towards marble trout than vice versa, and rainbow trout were clearly the dominant individuals. After simultaneous release in the river, marble trout immediately left the release area and spent twice as long time as rainbow trout until they settled in an area of the river; therefore, the release site was immediately occupied exclusively by rainbow trout. Thus, the dominant and aggressive behaviour of rainbow trout seen in the laboratory before release might have influenced marble trout's subsequent behaviour in the river, by marble trout leaving the areas occupied by rainbow trout and moving to locations further away from the release site. In the field, the marble trout occupied sites individually, whereas rainbow aggregated at a few locations. Rainbow trout showed higher movement activity in the morning compared to marble trout. There was a positive correlation between swimming speed in the laboratory and movement in the field for marble trout but not for rainbow trout. In conclusion, the results in this study support the need to end stocking of rainbow trout in rivers with native marble trout. To better understand the interaction between the species, and to develop efficient management plans to protect the native marble trout, reference behaviours should first be understood, and future research in sites where the two species do not co‐exist is needed. This is especially important for marble trout for which behavioural research and data are lacking.
Metataxonomic and metabolic evaluation of three water kefir microbiomes cultured in sugar cane juice
Authors: Wilches‐López Lisett , Correa‐Espinal Alexander , Pérez‐Monterroza Ezequiel José , Rojas Luisa F.
Published: January 2023

Three water kefir grains (WKG) C, B, M with higher heterogeneity in the consortia C and M, and different biodiversity, dominated mainly by the genus Lactobacillus were selected from three Colombian locations and evaluated metataxonomically and metabolically using sugar cane juice (SCJ) as a culture medium, the molecular characterization was performed by sequencing in Illumina Miseq, and microbial diversity used Mothur platforms. The objective was to evaluate the SCJ on the consortium and the bacterial and fungal diversity immersed in the WKG. Biomass and secondary metabolites were monitored during 152 h. Growth kinetic data were fitted to the Logistic, Richards, and Gompertz models. WKG C rRNA 16S sequencing by Simpson's index (0.298) evidenced low species biodiversity, dominated by Lactobacillus sp. In C (0.986), the ITS1 marker indicated a more heterogeneous community than B and M, with Saccharomyces sp. as the predominating species. Parameters of the Gompertz model fitted to C biomass were: μmax (0.032 h−1), latency time (1.736 h), and adaptation (6.48 h). WKG consortia B showed higher acetic acid and ethanol production with 5.269 and 0.333 g/L, respectively. SCJ is a suitable medium for Lactobacillus sp. and Saccharomyces sp. strains in WKG.