bluuebunny/crossref_metadata_2025 huggingface dataset:
An Unsupervised Machine Learning Clustering and Prediction of Differential Clinical Phenotypes of COVID-19 Patients Based on Blood Tests—A Hong Kong Population Study
Authors: Lau Kitty Yu-Yeung , Ng Kei-Shing , Kwok Ka-Wai , Tsia Kevin Kin-Man , Sin Chun-Fung , Lam Ching-Wan , Vardhanabhuti Varut
Published: February 2022

Background

To better understand the different clinical phenotypes across the disease spectrum in patients with COVID-19 using an unsupervised machine learning clustering approach.

Materials and Methods

A population-based retrospective study was conducted utilizing demographics, clinical characteristics, comorbidities, and clinical outcomes of 7,606 COVID-19–positive patients on admission to public hospitals in Hong Kong in the year 2020. An unsupervised machine learning clustering was used to explore this large cohort.

Results

Four clusters of differing clinical phenotypes based on data at initial admission was derived in which 86.6% of the deceased cases were aggregated in one of the clusters without prior knowledge of their clinical outcomes. Other distinctive clinical characteristics of this cluster were old age and high concurrent comorbidities as well as laboratory characteristics of lower hemoglobin/hematocrit levels, higher neutrophil, C-reactive protein, lactate dehydrogenase, and creatinine levels. The clinical patterns captured by the cluster analysis was validated on other temporally distinct cohorts in 2021. The phenotypes aligned with existing literature.

Conclusion

The study demonstrated the usefulness of unsupervised machine learning techniques with the potential to uncover latent clinical phenotypes. It could serve as a more robust classification for patient triaging and patient-tailored treatment strategies.
Difference in the Prevalence of Elevated Blood Pressure and Hypertension by References in Korean Children and Adolescents
Authors: Kim Jeong Yeon , Cho Heeyeon , Kim Jae Hyun
Published: February 2022

The prevalence of pediatric hypertension and obesity has increased over the past decades. Pediatric hypertension and obesity are associated with adult hypertension, metabolic syndrome, and cardiovascular disease. There are two main pediatric blood pressure (BP) classification guidelines, the “Clinical Practice Guideline for Screening and Management of High Blood Pressure in Children and Adolescents” (AAP 2017) and “2016 European Society of Hypertension guidelines for the management of high BP in children and adolescents” (ESH 2016). No study has classified Korean youths with cardiometabolic risk. This study analyzed the prevalence of high BP according to AAP 2017 (elevated BP and hypertension) and ESH 2016 (prehypertension and hypertension) in Korean children. Additionally, the cardiometabolic risk factors (CMRFs) were compared between children who were hypertensive in AAP 2017 but normotensive in ESH 2016 (upward reclassified) to those who were normotensive in both AAP 2017 and ESH 2016. Data were extracted from the Korea National Health and Nutrition Examination Survey, 2016–2018. A total of 1,858 children aged 10–17 years were included in the analysis. The prevalence of elevated BP/prehypertension and hypertension was 4.1 and 6.5% by ESH 2016, and 8.9 and 9.4% by AAP 2017 in Korean youth, respectively. The AAP 2017 reclassified 11.9% of youth in the upper BP class. When those upward reclassified youth were compared to those who were normotensive in both AAP 2017 and ESH 2016, reclassified youth were male predominant (77.1 vs. 49.6%, p < 0.001), older (14.6 vs. 13.8, p < 0.001) and showed higher body mass index (BMI) z-score (0.77 vs. 0.15, p < 0.001) and more overweight/obesity (14.0/30.6 vs. 13.3/6.4%, p < 0.001) and severe CMRFs (triglyceride 83.2 vs. 72.9 mg/dL, p = 0.011; high-density lipoprotein cholesterol 47.3 vs. 51.1 mg/dL, p < 0.001; alanine transaminase 21.7 IU/L vs. 14.7 IU/L, p = 0.001, uric acid 5.89 vs. 5.22 mg/dL, p < 0.001; metabolic syndrome 13.2 vs. 1%, p < 0.001). In conclusion, AAP 2017 showed a higher prevalence of abnormal BP in Korean youth, and those upward reclassified by AAP 2017 were more obese and had severe CMRFs than normotensive Korean children. The AAP 2017 could allow the early detection of Korean youth with more CMRFs.
High-Flow vs. Low-Flow Nasal Cannula in Reducing Hypoxemic Events During Bronchoscopic Procedures: A Systematic Review and Meta-Analysis
Authors: Sampsonas Fotios , Karamouzos Vasileios , Karampitsakos Theodoros , Papaioannou Ourania , Katsaras Matthaios , Lagadinou Maria , Zarkadi Eirini , Malakounidou Elli , Velissaris Dimitrios , Stratakos Grigorios , Tzouvelekis Argyrios
Published: February 2022

Introduction

High-flow nasal cannula (HFNC) oxygenation method has been proven to be successful in oxygenation of patients with respiratory failure and has exhibited clinical superiority compared to low-flow nasal cannula (LFNC).

Methods

We performed a systematic review and meta-analysis to evaluate the potential favorable impact of HFNC oxygenation during bronchoscopy and related procedures like endobronchial ultrasound-transbronchial needle aspiration. Only randomized control trials (RCTs) were included in the meta-analysis.

Results

Six randomized control trials with 1,170 patients were included in this meta-analysis. Patients who underwent bronchoscopy with the use of high-flow nasal cannula experienced less hypoxemic events/desaturations, less procedural interruptions and pneumothoraxes compared to patients under low-flow nasal cannula treatment. This beneficial effect of HFNC in hypoxemic events was persistent 10 min after the end of procedure.

Conclusion

The high-flow nasal cannula (HFNC) oxygenation method could reduce hypoxemic events and related peri- and post-bronchoscopic complications.
Demodex folliculorum Infestation in Meibomian Gland Dysfunction Related Dry Eye Patients
Authors: Hao Yiran , Zhang Xiaoyu , Bao Jiayu , Tian Lei , Jie Ying
Published: February 2022

Objective

To report the influence of Demodex folliculorum (D. folliculorum) infestation in patients with meibomian gland dysfunction (MGD) related dry eye and the associations of the infestation with MGD related dry eye.

Methods

Eyelashes (three from the upper eyelid and three from the lower eyelid) from 119 eyes of 119 patients diagnosed with MGD related dry eye were examined under a light microscope. There were 68 eyes of 68 patients with MGD related dry eye and D. folliculorum infestation (Demodex positive group) and 51 eyes of 51 patients without infestation (Demodex negative group). All patients completed an Ocular Surface Disease Index (OSDI) questionnaire and underwent tests for dry eye and MGD. The tests included fluorescein tear breakup time (TBUT), corneal fluorescein staining, Schirmer I test (SIT), lid margin abnormalities, meibum expression assessment, and meibomian gland dropout.

Results

The scores for OSDI, corneal fluorescein staining, lid margin abnormalities, meibum expression, and meibomian gland dropout were significantly higher (all P < 0.05), while TBUT was significantly shorter in the Demodex positive group compared to the Demodex negative group (P = 0.020). The SIT values did not significantly differ between groups. Chalazion was significantly more prevalent in the Demodex positive group. The number of D. folliculorum was positively correlated with all three MGD parameters (P ≤ 0.035), OSDI; corneal fluorescein scores, and it was inversely correlated with BUT. The correlation for SIT was R2 = 0.075 (P = 0.064).

Conclusion

Demodex folliculorum infestation is possibly one of the key contributors in the pathogenesis of MGD related dry eye, and a higher prevalence of chalazion was found in D. folliculorum infected patients. The possible causal role of D. folliculorum infestation needs to be further studied.
Mitogen-Activated Protein Kinase CsPMK1 Is Essential for Pepper Fruit Anthracnose by Colletotrichum scovillei
Authors: Fu Teng , Shin Jong-Hwan , Lee Noh-Hyun , Lee Kwang Ho , Kim Kyoung Su
Published: February 2022

The phytopathogenic fungus Colletotrichum scovillei, belonging to the Colletotrichum acutatum species complex, causes severe anthracnose disease on several fruits, including chili pepper (Capsicum annuum). However, the molecular mechanisms underlying the development and pathogenicity of Colletotrichum scovillei are unclear. The conserved Fus3/Kss1-related MAPK regulates fungal development and pathogenicity. Here, the role of CsPMK1, orthologous to Fus3/Kss1, was characterized by phenotypic comparison of a target deletion mutant (ΔCspmk1). The mycelial growth and conidiation of ΔCspmk1 were normal compared to that of the wild type. ΔCspmk1 produced morphologically abnormal conidia, which were delayed in conidial germination. Germinated conidia of ΔCspmk1 failed to develop appressoria on inductive surfaces of hydrophobic coverslips and host plants. ΔCspmk1 was completely defective in infectious growth, which may result from failure to suppress host immunity. Furthermore, ΔCspmk1 was impaired in nuclear division and lipid mobilization during appressorium formation, in response to a hydrophobic surface. CsPMK1 was found to interact with CsHOX7, a homeobox transcription factor essential for appressorium formation, via a yeast two-hybridization analysis. Taken together, these findings suggest that CsPMK1 is required for fungal development, stress adaptation, and pathogenicity of C. scovillei.
Interactions Between Intestinal Microbiota and Neural Mitochondria: A New Perspective on Communicating Pathway From Gut to Brain
Authors: Zhu Yao , Li Ying , Zhang Qiang , Song Yuanjian , Wang Liang , Zhu Zuobin
Published: February 2022

Many studies shown that neurological diseases are associated with neural mitochondrial dysfunctions and microbiome composition alterations. Since mitochondria emerged from bacterial ancestors during endosymbiosis, mitochondria, and bacteria had analogous genomic characteristics, similar bioactive compounds and comparable energy metabolism pathways. Therefore, it is necessary to rationalize the interactions of intestinal microbiota with neural mitochondria. Recent studies have identified neural mitochondrial dysfunction as a critical pathogenic factor for the onset and progress of multiple neurological disorders, in which the non-negligible role of altered gut flora composition was increasingly noticed. Here, we proposed a new perspective of intestinal microbiota – neural mitochondria interaction as a communicating channel from gut to brain, which could help to extend the vision of gut-brain axis regulation and provide additional research directions on treatment and prevention of responsive neurological disorders.
Physiological and Molecular Characterization of an Oxidative Stress-Resistant Saccharomyces cerevisiae Strain Obtained by Evolutionary Engineering
Authors: Kocaefe-Özşen Nazlı , Yilmaz Bahtiyar , Alkım Ceren , Arslan Mevlüt , Topaloğlu Alican , Kısakesen Halil l̇brahim , Gülsev Erdinç , Çakar Z. Petek
Published: February 2022

Oxidative stress is a major stress type observed in yeast bioprocesses, resulting in a decrease in yeast growth, viability, and productivity. Thus, robust yeast strains with increased resistance to oxidative stress are in highly demand by the industry. In addition, oxidative stress is also associated with aging and age-related complex conditions such as cancer and neurodegenerative diseases. Saccharomyces cerevisiae, as a model eukaryote, has been used to study these complex eukaryotic processes. However, the molecular mechanisms underlying oxidative stress responses and resistance are unclear. In this study, we have employed evolutionary engineering (also known as adaptive laboratory evolution – ALE) strategies to obtain an oxidative stress-resistant and genetically stable S. cerevisiae strain. Comparative physiological, transcriptomic, and genomic analyses of the evolved strain were then performed with respect to the reference strain. The results show that the oxidative stress-resistant evolved strain was also cross-resistant against other types of stressors, including heat, freeze-thaw, ethanol, cobalt, iron, and salt. It was also found to have higher levels of trehalose and glycogen production. Further, comparative transcriptomic analysis showed an upregulation of many genes associated with the stress response, transport, carbohydrate, lipid and cofactor metabolic processes, protein phosphorylation, cell wall organization, and biogenesis. Genes that were downregulated included those related to ribosome and RNA processing, nuclear transport, tRNA, and cell cycle. Whole genome re-sequencing analysis of the evolved strain identified mutations in genes related to the stress response, cell wall organization, carbohydrate metabolism/transport, which are in line with the physiological and transcriptomic results, and may give insight toward the complex molecular mechanisms of oxidative stress resistance.
Fungal Diversity in the Soil of the Oxytropis glacialis Root System on the Qinghai-Tibet Plateau
Authors: Cao Peng-xi , Liu Yixuan , Ma Hong-mei , Zhao Ning , Chen Shu-ting , Xu Guo-qi , Liu Xing
Published: February 2022

Because of swainonine-producing endophytic fungal, Oxytropis glacialis is one of the main poisonous weeds in the alpine grassland and desert grassland of the Qinghai-Tibet Plateau (QTP). It has a severe impact on grassland degradation on the QTP. In this manuscript, the Internally Transcribed Spacer (ITS) region of fungal communities in the soil of the O. glacialis root system was sequenced by high-throughput sequencing and analyzed by bioinformatics methods. The physical and chemical properties of the soil samples were analyzed in combination with the fungal diversity and its relationship with the soil physical and chemical factors. The results showed that the soil fungal community in the O. glacialis root system are rich in diversity in different ecological environments and are most affected by the soil pH value and organic matter. The swainonine-producing fungal Embellisia oxytropis was first detected in the soil of the O. glacialis root system. This finding provides data to support the next step in demonstrating the horizontal spread of swainone-producing fungal from O. glacialis to soil. In addition, a stable network of core flora has a facilitating effect on the formation of O. glacialis as a dominant species in alpine ecosystems.
Host Plant Species Influences the Composition of Milkweed and Monarch Microbiomes
Authors: Hansen Thorsten E. , Enders Laramy S.
Published: February 2022

Plants produce defensive chemicals for protection against insect herbivores that may also alter plant and insect associated microbial communities. However, it is unclear how expression of plant defenses impacts the assembly of insect and plant microbiomes, for example by enhancing communities for microbes that can metabolize defensive chemicals. Monarch butterflies (Danaus plexippus) feed on milkweed species (Asclepias spp.) that vary in production of toxic cardiac glycosides, which could alter associated microbiomes. We therefore sought to understand how different milkweed species, with varying defensive chemical profiles, influence the diversity and composition of monarch and milkweed (root and leaf) bacterial communities. Using a metabarcoding approach, we compared rhizosphere, phyllosphere and monarch microbiomes across two milkweed species (Asclepias curassavica, Asclepias syriaca) and investigated top-down effects of monarch feeding on milkweed microbiomes. Overall, monarch feeding had little effect on host plant microbial communities, but each milkweed species harbored distinct rhizosphere and phyllosphere microbiomes, as did the monarchs feeding on them. There was no difference in diversity between plants species for any of the microbial communities. Taxonomic composition significantly varied between plant species for rhizospheres, phyllospheres, and monarch microbiomes and no dispersion were detected between samples. Interestingly, phyllosphere and monarch microbiomes shared a high proportion of bacterial taxa with the rhizosphere (88.78 and 95.63%, respectively), while phyllosphere and monarch microbiomes had fewer taxa in common. Overall, our results suggest milkweed species select for unique sets of microbial taxa, but to what extent differences in expression of defensive chemicals directly influences microbiome assembly remains to be tested. Host plant species also appears to drive differences in monarch caterpillar microbiomes. Further work is needed to understand how monarchs acquire microbes, for example through horizontal transfer during feeding on leaves or encountering soil when moving on or between host plants.
Plant-Mycorrhizal Fungi Interactions in Phytoremediation of Geogenic Contaminated Soils
Authors: Ma Ying , Ankit  , Tiwari Jaya , Bauddh Kuldeep
Published: February 2022

Soil contamination by geogenic contaminants (GCs) represents an imperative environmental problem. Various soil remediation methods have been successfully employed to ameliorate the health risks associated with GCs. Phytoremediation is considered as an eco-friendly and economical approach to revegetate GC-contaminated soils. However, it is a very slow process, as plants take a considerable amount of time to gain biomass. Also, the process is limited only to the depth and surface area of the root. Inoculation of arbuscular mycorrhizal fungi (AMF) with remediating plants has been found to accelerate the phytoremediation process by enhancing plant biomass and their metal accumulation potential while improving the soil physicochemical and biological characteristics. Progress in the field application is hindered by a lack of understanding of complex interactions between host plant and AMF that contribute to metal detoxification/(im)mobilization/accumulation/translocation. Thus, this review is an attempt to reveal the underlying mechanisms of plant-AMF interactions in phytoremediation.
Melanin Promotes Spore Production in the Rice Blast Fungus Magnaporthe oryzae
Authors: Huang Pengyun , Cao Huijuan , Li Yan , Zhu Siyi , Wang Jing , Wang Qing , Liu Xiaohong , Lin Fu-Cheng , Lu Jianping
Published: February 2022

The rice blast pathogen, Magnaporthe oryzae, spreads through spores and invades rice through appressoria. Melanin is necessary for an appressorium to penetrate plant cells, but there are many unknown aspects of its role in fungal conidiation. In this study, we confirmed that melanin promotes spore production in M. oryzae, and that this effect is related to the background melanin content of wild-type strains. In the wild-type 70-15 strain with low melanin content of aerial hyphae, increased melanin synthesis promoted sporulation. In contrast, increased melanin synthesis in the wild-type Guy11 strain, which has higher melanin content, did not promote sporulation. The transcription factor Cnf1 (conidial production negative regulatory factor 1), which negatively regulates melanin synthesis, has opposite effects in conidiophore differentiation of Guy11 and 70-15. Deletion of CNF1 did not abolish the defects of Δcos1 and Δhox2 (where COS1/conidiophore stalk-less 1 or HOX2/homeodomain protein 2 was deleted) in conidiation, while increased the conidiation of Δgcc1 and Δgcf3 (where GCC1/growth, conidiation and cell wall regulatory factor 1, or GCF3/growth and conidiation regulatory factor 3 was deleted). Pig1 (pigment of Magnaporthe 1) regulates the melanin synthesis of hyphae but not of conidiophores, spores, or appressoria. Deletion of the same gene in different wild-type strains can lead to different phenotypes, partly because of differences in melanin content between fungal strains. Overall, this study reveals the functional diversity and complexity of melanin in different M. oryzae strains.
Suppression of Neuroinflammation Attenuates Persistent Cognitive and Neurogenic Deficits in a Rat Model of Cardiopulmonary Bypass
Authors: Wang Yi , Machizawa Maro G. , Lisle Turner , Williams Cedric L. , Clarke Ryon , Anzivino Matthew , Kron Irving , Lee Kevin S.
Published: February 2022

Post-operative cognitive dysfunction (POCD) can be a serious surgical complication, and patients undergoing cardiac procedures are at particular risk for POCD. This study examined the effect of blocking neuroinflammation on behavioral and neurogenic deficits produced in a rat model of cardiopulmonary bypass (CPB). Minocycline, a drug with established anti-inflammatory activity, or saline was administered daily for 30 days post-CPB. Treatment with minocycline reduced the number of activated microglia/macrophages observed in the dentate gyrus of the hippocampus at 6 months post-CPB, consistent with an anti-inflammatory action in this CPB model. Behavioral testing was conducted at 6 months post-CPB utilizing a win-shift task on an 8-arm radial maze. Minocycline-treated animals performed significantly better than saline-treated animals on this task after CPB. In addition, the CPB-induced reduction in adult neurogenesis was attenuated in the minocycline-treated animals. Together, these findings indicate that suppressing neuroinflammation during the early post-surgical phase can limit long-term deficits in both behavioral and neurogenic outcomes after CPB.
A Subset of Nucleus Accumbens Neurons Receiving Dense and Functional Prelimbic Cortical Input Are Required for Cocaine Seeking
Authors: Siemsen Benjamin M. , Barry Sarah M. , Vollmer Kelsey M. , Green Lisa M. , Brock Ashley G. , Westphal Annaka M. , King Raven A. , DeVries Derek M. , Otis James M. , Cowan Christopher W. , Scofield Michael D.
Published: February 2022

Background

Prelimbic cortical projections to the nucleus accumbens core are critical for cue-induced cocaine seeking, but the identity of the accumbens neuron(s) targeted by this projection, and the transient neuroadaptations contributing to relapse within these cells, remain unknown.

Methods

Male Sprague-Dawley rats underwent cocaine or sucrose self-administration, extinction, and cue-induced reinstatement. Pathway-specific chemogenetics, patch-clamp electrophysiology, in vivo electrochemistry, and high-resolution confocal microscopy were used to identify and characterize a small population of nucleus accumbens core neurons that receive dense prelimbic cortical input to determine their role in regulating cue-induced cocaine and natural reward seeking.

Results

Chemogenetic inhibition of prelimbic cortical projections to the nucleus accumbens core suppressed cue-induced cocaine relapse and normalized real-time cue-evoked increases in accumbens glutamate release to that of sucrose seeking animals. Furthermore, chemogenetic inhibition of the population of nucleus accumbens core neurons receiving the densest prelimbic cortical input suppressed cocaine, but not sucrose seeking. These neurons also underwent morphological plasticity during the peak of cocaine seeking in the form of dendritic spine expansion and increased ensheathment by astroglial processes at large spines.

Conclusion

We identified and characterized a unique subpopulation of nucleus accumbens neurons that receive dense prelimbic cortical input. The functional specificity of this subpopulation is underscored by their ability to mediate cue-induced cocaine relapse, but not sucrose seeking. This subset of cells represents a novel target for addiction therapeutics revealed by anterograde targeting to interrogate functional circuits imbedded within a known network.
Intermediate-Intensity Autologous Hematopoietic Stem Cell Transplantation Reduces Serum Neurofilament Light Chains and Brain Atrophy in Aggressive Multiple Sclerosis
Authors: Mariottini Alice , Marchi Leonardo , Innocenti Chiara , Di Cristinzi Maria , Pasca Matteo , Filippini Stefano , Barilaro Alessandro , Mechi Claudia , Fani Arianna , Mazzanti Benedetta , Biagioli Tiziana , Materozzi Francesca , Saccardi Riccardo , Massacesi Luca , Repice Anna Maria
Published: February 2022

Background

Autologous haematopoietic stem cell transplantation (AHSCT) is highly effective in reducing new inflammatory activity in aggressive multiple sclerosis (MS). A remarkable decrease of serum neurofilament light chains (sNfL) concentration, a marker of axonal damage, was reported in MS following high-intensity regimen AHSCT, but hints for potential neurotoxicity had emerged. sNfL and brain atrophy were therefore analysed in a cohort of patients with aggressive MS treated with intermediate-intensity AHSCT, exploring whether sNfL might be a reliable marker of disability progression independent from new inflammation (i.e. relapses and/or new/gadolinium-enhancing MRI focal lesions).

Methods

sNfL concentrations were measured using SIMOA methodology in peripheral blood from relapsing-remitting (RR-) or secondary-progressive (SP-) MS patients undergoing AHSCT (MS AHSCT), collected before transplant and at months 6 and 24 following the procedure. sNfL measured at a single timepoint in SP-MS patients not treated with AHSCT without recent inflammatory activity (SP-MS CTRL) and healthy subjects (HD) were used as controls. The rate of brain volume loss (AR-BVL) was also evaluated by MRI in MS AHSCT cases.

Results

Thirty-eight MS AHSCT (28 RR-MS; 10 SP-MS), 22 SP-MS CTRL and 19 HD were included. Baseline median sNfL concentrations were remarkably higher in the MS AHSCT than in the SP-MS CTRL and HD groups (p = 0.005 and <0.0001, respectively), and levels correlated with recent inflammatory activity. After a marginal (not significant) median increase observed at month 6, at month 24 following AHSCT sNfL concentrations decreased compared to baseline by median 42.8 pg/mL (range 2.4–217.3; p = 0.039), reducing by at least 50% in 13 cases, and did not differ from SP-MS CTRL (p = 0.110) but were still higher than in HD (p < 0.0001). Post-AHSCT AR-BVL normalised in 55% of RR-MS and in 30% of SP-MS. The effectiveness and safety of AHSCT were aligned with the literature.

Conclusion

sNfL concentrations correlated with recent inflammatory activity and were massively and persistently reduced by intermediate-intensity AHSCT. Association with response to treatment assessed by clinical or MRI outcomes was not observed, suggesting a good sensitivity of sNfL for recent inflammatory activity but low sensitivity in detecting ongoing axonal damage independent from new focal inflammation.
Core Sets of Kinematic Variables to Consider for Evaluation of Gait Post-stroke
Authors: Nedergård Heidi , Schelin Lina , Liebermann Dario G. , Johansson Gudrun M. , Häger Charlotte K.
Published: February 2022

Background

Instrumented gait analysis post-stroke is becoming increasingly more common in research and clinics. Although overall standardized procedures are proposed, an almost infinite number of potential variables for kinematic analysis is generated and there remains a lack of consensus regarding which are the most important for sufficient evaluation. The current aim was to identify a discriminative core set of kinematic variables for gait post-stroke.

Methods

We applied a three-step process of statistical analysis on commonly used kinematic gait variables comprising the whole body, derived from 3D motion data on 31 persons post-stroke and 41 non-disabled controls. The process of identifying relevant core sets involved: (1) exclusion of variables for which there were no significant group differences; (2) systematic investigation of one, or combinations of either two, three, or four significant variables whereby each core set was evaluated using a leave-one-out cross-validation combined with logistic regression to estimate a misclassification rate (MR).

Results

The best MR for one single variable was shown for theDuration of single-support(MR 0.10) orDuration of 2nd double-support(MR 0.11)phase, corresponding to an 89–90% probability of correctly classifying a person as post-stroke/control. AddingPelvissagittal ROMto either of the variablesSelf-selected gait speedorStride length, alternatively addingAnkle sagittal ROMto theDuration of single-stance phase, increased the probability of correctly classifying individuals to 93–94% (MR 0.06). Combining three variables decreased the MR further to 0.04, suggesting a probability of 96% for correct classification. These core sets contained: (1) a spatial (Stride/Step length) or a temporal variable (Self-selected gait speed/Stance time/Swing timeorDuration of 2nd double-support), (2)Pelvissagittal ROMorAnkle plantarflexion during push-off, and (3)Arm Posture ScoreorCadenceor a knee/shoulder joint angle variable. Adding a fourth variable did not further improve the MR.

Conclusion

A core set combining a few crucial kinematic variables may sufficiently evaluate post-stroke gait and should receive more attention in rehabilitation. Our results may contribute toward a consensus on gait evaluation post-stroke, which could substantially facilitate future diagnosis and monitoring of rehabilitation progress.
Neural Correlates of Attachment Representation in Patients With Borderline Personality Disorder Using a Personalized Functional Magnet Resonance Imaging Task
Authors: Bernheim Dorothee , Buchheim Anna , Domin Martin , Mentel Renate , Lotze Martin
Published: February 2022

Background

Fear of abandonment and aloneness play a key role in the clinical understanding interpersonal and attachment-specific problems in patients with borderline personality disorder (BPD) and has been investigated in previous functional Magnet Resonance Imaging (fMRI) studies. The aim of the present study was to examine how different aspects of attachment representations are processed in BPD, by using for the first time an fMRI attachment paradigm including personalized core sentences from the participants’ own attachment stories. We hypothesized that BPD patients would show increased functional involvement of limbic brain regions associated with fear and pain (e.g., the amygdala and the anterior cingulate cortex) when presented personalized attachment relevant stimuli representing loneliness compared to healthy controls (HC).

Methods

We examined the attachment classifications of 26 female BPD patients and 26 female HC using the Adult Attachment Projective Picture System (AAP). We used an fMRI-adapted attachment paradigm to investigate the neural correlates of attachment. All participants were presented three personalized (vs. neutral) sentences extracted from their AAP attachment narrative, combined with standardized AAP pictures representing being alone (monadic) or in interactive (dyadic) attachment situations.

Results

As expected, the classification of unresolved attachment was significantly greater in BPD compared to HC. BPD patients showed increased fMRI-activation in brain areas associated with fear, pain, and hyperarousal than HC when presented with personalized attachment-relevant alone stimuli. In particular, pictures with monadic attachment situations induced greater anterior medial cingulate cortex, anterior insula, amygdala, thalamus and superior temporal gyrus activation in the patient group.

Conclusion

The results point to increased fMRI-activation in areas processing emotional distress and painful experiences in BPD patients. In particular, the emotional cascade reflecting attachment distress was evoked by combining monadic pictures, representing abandonment and aloneness, with the patients’ personalized narrative material. Our results confirmed and replicated previous results that illustrate once again the high relevance of aloneness and feelings of abandonment for BPD in the context of attachment trauma. Moreover, our results support the hypothesis of hypermentalization in response to attachment distress as a core feature of social-cognitive impairment in BPD associated with common treatment implications across different therapeutic orientations.
The BrainScaleS-2 Accelerated Neuromorphic System With Hybrid Plasticity
Authors: Pehle Christian , Billaudelle Sebastian , Cramer Benjamin , Kaiser Jakob , Schreiber Korbinian , Stradmann Yannik , Weis Johannes , Leibfried Aron , Müller Eric , Schemmel Johannes
Published: February 2022

Since the beginning of information processing by electronic components, the nervous system has served as a metaphor for the organization of computational primitives. Brain-inspired computing today encompasses a class of approaches ranging from using novel nano-devices for computation to research into large-scale neuromorphic architectures, such as TrueNorth, SpiNNaker, BrainScaleS, Tianjic, and Loihi. While implementation details differ, spiking neural networks—sometimes referred to as the third generation of neural networks—are the common abstraction used to model computation with such systems. Here we describe the second generation of the BrainScaleS neuromorphic architecture, emphasizing applications enabled by this architecture. It combines a custom analog accelerator core supporting the accelerated physical emulation of bio-inspired spiking neural network primitives with a tightly coupled digital processor and a digital event-routing network.
Executive Performance Is Associated With Rest-Activity Rhythm in Nurses Working Rotating Shifts
Authors: Zhao Xiuli , Tang Quan , Feng Zhengzhi , Zhào Hóngyi
Published: February 2022

Purpose

Rest-activity rhythms (RAR) is one of the most fundamental biological patterns that influence basic physical and mental health, as well as working performance. Nowadays, with the utilization of actigraphy device in detecting and analyzing RAR objectively, evidence has confirmed that RAR could be interrupted by shift work. Nurses need to participate shift work in their daily routine. The aim of the present study is to identify the RAR of nurses working rotating shifts and find out the relationship between RAR and executive function.

Methods

A total of 11 female nurses on day-shift (DS), 11 female nurses on rotating-shift (RS) were recruited. Demographic features, non-parametric variables of RAR as well as sleep variables according to actigraphy data, and a series of cognitive function evaluations during work time were collected.

Results

The Student’s t-test comparison revealed that RS group nurses showed significant shorter total sleep time (TST), lower level of interdaily stability (IS) and relative amplitude (RA), as well as poorer executive performance compared with DS nurses. The linear regression analysis demonstrated that several aspects of executive performance such as choice reaction test (CRT) (reflecting attention and concentration) and trail making test (TMT) -B (reflecting cognitive flexibility) were associated with IS in RS group nurses.

Conclusion

These results elucidated that RAR was disrupted for nurses working rotating shifts, and executive performance was associated with IS from day to day in nurses working rotating shifts.
Postnatal Development of Centrifugal Inputs to the Olfactory Bulb
Authors: Kostka Johanna K. , Bitzenhofer Sebastian H.
Published: February 2022

Processing in primary sensory areas is influenced by centrifugal inputs from higher brain areas, providing information about behavioral state, attention, or context. Activity in the olfactory bulb (OB), the first central processing stage of olfactory information, is dynamically modulated by direct projections from a variety of areas in adult mice. Despite the early onset of olfactory sensation compared to other senses, the development of centrifugal inputs to the OB remains largely unknown. Using retrograde tracing across development, we show that centrifugal projections to the OB are established during the postnatal period in an area-specific manner. While feedback projections from the piriform cortex (PIR) are already present shortly after birth, they strongly increase in number during postnatal development with an anterior-posterior gradient. Contralateral projections from the anterior olfactory nucleus (AON) are present at birth but only appeared postnatally for the nucleus of the lateral olfactory tract (nLOT). Numbers of OB projecting neurons from the lateral entorhinal cortex (LEC), ventral hippocampus, and cortical amygdala (CoA) show a sudden increase at the beginning of the second postnatal week and a delayed development compared to more anterior areas. These anatomical data suggest that limited top-down influence on odor processing in the OB may be present at birth, but strongly increases during postnatal development and is only fully established later in life.
Modulation of Gamma Spectral Amplitude and Connectivity During Reaching Predicts Peak Velocity and Movement Duration
Authors: Tatti Elisa , Ferraioli Francesca , Cacciola Alberto , Chan Cameron , Quartarone Angelo , Ghilardi Maria Felice
Published: February 2022

Modulation of gamma oscillations recorded from the human motor cortex and basal ganglia appears to play a key role in movement execution. However, there are still major questions to be answered about the specific role of cortical gamma activity in both the planning and execution of movement features such as the scaling of peak velocity and movement time. In this study, we characterized movement-related gamma oscillatory dynamics and its relationship with kinematic parameters based on 256-channels EEG recordings in 64 healthy subjects while performing fast and uncorrected reaching movements to targets located at three distances. In keeping with previous studies, we found that movement-related gamma synchronization occurred during movement execution. As a new finding, we showed that gamma synchronization occurred also before movement onset, with planning and execution phases involving different gamma peak frequencies and topographies. Importantly, the amplitude of gamma synchronization in both planning and execution increased with target distance and predicted peak velocity and movement time. Additional analysis of phase coherence revealed a gamma-coordinated long-range network involving occipital, frontal and central regions during movement execution that was positively related to kinematic features. This is the first evidence in humans supporting the notion that gamma synchronization amplitude and phase coherence pattern can reliably predict peak velocity amplitude and movement time. Therefore, these findings suggest that cortical gamma oscillations have a crucial role for the selection, implementation and control of the appropriate kinematic parameters of goal-directed reaching movements.
Disrupted Functional Connectivity of the Amygdala Predicts the Efficacy of Non-steroidal Anti-inflammatory Drugs in Migraineurs Without Aura
Authors: Wei Heng-Le , Xu Chen-Hui , Wang Jin-Jin , Zhou Gang-Ping , Guo Xi , Chen Yu-Chen , Yu Yu-Sheng , He Zhen-Zhen , Yin Xindao , Li Junrong , Zhang Hong
Published: February 2022

Machine learning (ML) has been largely applied for predicting migraine classification. However, the prediction of efficacy of non-steroidal anti-inflammatory drugs (NSAIDs) in migraine is still in the early stages. This study aims to evaluate whether the combination of machine learning and amygdala-related functional features could help predict the efficacy of NSAIDs in patients with migraine without aura (MwoA). A total of 70 MwoA patients were enrolled for the study, including patients with an effective response to NSAIDs (M-eNSAIDs, n = 35) and MwoA patients with ineffective response to NSAIDs (M-ieNSAIDs, n = 35). Furthermore, 33 healthy controls (HCs) were matched for age, sex, and education level. The study participants were subjected to resting-state functional magnetic resonance imaging (fMRI) scanning. Disrupted functional connectivity (FC) patterns from amygdala-based FC analysis and clinical characteristics were considered features that could promote classification through multivariable logistic regression (MLR) and support vector machine (SVM) for predicting the efficacy of NSAIDs. Further, receiver operating characteristic (ROC) curves were drawn to evaluate the predictive ability of the models. The M-eNSAIDs group exhibited enhanced FC with ipsilateral calcarine sulcus (CAL), superior parietal gyrus (SPG), paracentral lobule (PCL), and contralateral superior frontal gyrus (SFG) in the left amygdala. However, the M-eNSAIDs group showed decreased FC with ipsilateral caudate nucleus (CAU), compared to the M-ieNSAIDs group. Moreover, the M-eNSAIDs group showed higher FC with left pre-central gyrus (PreCG) and post-central gyrus (PoCG) compared to HCs. In contrast, the M-ieNSAIDs group showed lower FC with the left anterior cingulate cortex (ACC) and right SFG. Furthermore, the MwoA patients showed increased FC with the left middle frontal gyrus (MFG) in the right amygdala compared to HCs. The disrupted left amygdala-related FC patterns exhibited significant correlations with migraine characteristics in the M-ieNSAIDs group. The MLR and SVM models discriminated clinical efficacy of NSAIDs with an area under the curve (AUC) of 0.891 and 0.896, sensitivity of 0.971 and 0.833, and specificity of 0.629 and 0.875, respectively. These findings suggest that the efficacy of NSAIDs in migraine could be predicted using ML algorithm. Furthermore, this study highlights the role of amygdala-related neural function in revealing underlying migraine-related neuroimaging mechanisms.
Recurrent Connections Might Be Important for Hierarchical Categorization
Authors: Matsumoto Narihisa , Taguchi Yusuke , Shimizu Masaumi , Katakami Shun , Okada Masato , Sugase-Miyamoto Yasuko
Published: February 2022

Visual short-term memory is an important ability of primates and is thought to be stored in area TE. We previously reported that the initial transient responses of neurons in area TE represented information about a global category of faces, e.g., monkey faces vs. human faces vs. simple shapes, and the latter part of the responses represented information about fine categories, e.g., facial expression. The neuronal mechanisms of hierarchical categorization in area TE remain unknown. For this study, we constructed a combined model that consisted of a deep neural network (DNN) and a recurrent neural network and investigated whether this model can replicate the time course of hierarchical categorization. The visual images were stored in the recurrent connections of the model. When the visual images with noise were input to the model, the model outputted the time course of the hierarchical categorization. This result indicates that recurrent connections in the model are important not only for visual short-term memory but for hierarchical categorization, suggesting that recurrent connections in area TE are important for hierarchical categorization.
A Comprehensive Risk Assessment and Stratification Model of Papillary Thyroid Carcinoma Based on the Autophagy-Related LncRNAs
Authors: Mu Yongrun , Song Fuling , Yuan Kai , Zhang Zili , Lu Yan , Fu Rongzhan , Zhou Dongsheng
Published: February 2022

Background

Papillary thyroid carcinoma (PTC) is one of the most common malignant carcinomas in the endocrine system, and it has a growing incidence worldwide. Despite the development of diagnosis and treatment modalities for thyroid carcinoma, the outcome remains uncertain. Autophagy participates in the process of cancer invasion, malignancy, metastasis, and drug resistance. Emerging research has shown that long noncoding RNAs (lncRNAs) play an important role in the process of different types of cancers. However, the interaction between the process of autophagy and lncRNA and the value of autophagy-related lncRNA for risk assessment, prediction of drug sensitivity, and prognosis prediction in PTC patients remains unknown.

Materials and Methods

We screened 1,283 autophagy-related lncRNAs and identified 144 lncRNAs with prognostic value in The Cancer Genome Atlas (TCGA) cohorts. Univariate and multivariate Cox regression analyses were used to establish the prognosis-related autophagy-related lncRNA risk classification consisting of 10 lncRNAs to indicate the level of risk, according to which the patients were grouped into high-risk group and low risk-group.

Results

The high-risk group had dramatically worse overall survival compared with the low-risk group. Cox regression analysis was performed to confirm the independent prognostic value of the autophagy-related lncRNA risk stratification, and the time-dependent receiver operating characteristic curves of the risk stratification were 0.981 (1 year), 0.906 (3 years), and 0.963 (5 years). LncRNA CRNDE (LINC00180) is overexpressed in the tumor, and its high expression matched with poorer survival state. So, we chose it for further experiment. Finally, knockdown of the CRNDE in PTC increased the sensitivity to sorafenib.

Conclusion

Collectively, we successfully established a novel risk stratification for PTC based on the expression profiles of autophagy-related lncRNAs.
COL8A1 Promotes NSCLC Progression Through IFIT1/IFIT3-Mediated EGFR Activation
Authors: Zan Xiangyi , Li Shuyan , Wei Shixiong , Gao Liping , Zhao Lanting , Yan Xiaoxia , Zhao Yan , Shi Junnian , Wang Yuping , Liu Rong , Zhang Yuanyi , Wan Yixin , Zhou Yongning
Published: February 2022

Activation of EGFR is a major risk factor for non-small cell lung cancer (NSCLC). Understanding the molecular events promoting EGFR activation can help us gain more insights into the progression of NSCLC. In this study, we demonstrate that collagen type VIII alpha 1 chain (COL8A1), an extracellular matrix component, was overexpressed in NSCLC. In NSCLC cells, knockdown of COL8A1 suppressed cell growth, cycle progression, and migration, and induced cell apoptosis. While COL8A1 overexpression promoted cell proliferation and inhibited cell apoptosis. In addition, we found that COL8A1 depletion reduced interferon response signaling and downregulated (IFIT1) and interferon-induced proteins with tetratricopeptide repeats 3 (IFIT3). Moreover, we indicated that COL8A1 could upregulate IFIT1 and IFIT3 mediated EGFR activation in vitro and in vivo. Lastly, there was a positive correlation among COL8A1, IFIT1, and IFIT3 expression, and EGFR activity in patients with NSCLC. Overall, our data demonstrate that COL8A1 contributes to NSCLC proliferation and invasion through EGFR activation, dependent on IFIT1 and IFIT3 expression.
AKR1B10 as a Potential Novel Serum Biomarker for Breast Cancer: A Pilot Study
Authors: Cao Zhe , Delfino Kristin , Tiwari Vivek , Wang Xin , Hannan Abdul , Zaidi Fawwad , McClintock Andrew , Robinson Kathy , Zhu Yun , Gao John , Cao Deliang , Rao Krishna
Published: February 2022

Background

Aldo-keto reductase 1B10 (AKR1B10) is a secretory protein that is upregulated in breast cancer.

Objective

This case-controlled pilot study evaluated the serum level of AKR1B10 in healthy women and patients with a localized or metastatic breast cancer.

Methods

AKR1B10 levels were measured by ELISA and IHC in several patient cohorts.

Results

Our data showed that serum AKR1B10 was significantly elevated in patients with localized (6.72 ± 0.92 ng/ml) or metastatic (7.79 ± 1.13 ng/ml) disease compared to cancer-free healthy women (1.69 ± 0.17 ng/ml) (p<0.001); the serum AKR1B10 was correlated with its expression in tumor tissues, but not with the tumor burden, molecular subtypes or histological stages. After surgical removal of primary tumors, the serum AKR1B10 was rapidly decreased within 3 days and plateaued at a level similar to that of healthy controls in most patients. ROC curve analysis suggested the optimal diagnostic cut-off value of serum AKR1B10 at 3.456 ng/ml with AUC 0.9045 ± 0.0337 (95% CI 0.8384 – 0.9706), sensitivity 84.75% (95% CI 73.01% to 92.78%), and specificity 93.88% (95% CI 83.13% to 98.72%).

Conclusions

These data indicate the potential value of serum AKR1B10 as a biomarker of breast cancer.