bluuebunny/crossref_metadata_2025 huggingface dataset:
Genomic insights and antimicrobial resistance profiles of CRKP and non-CRKP isolates in a Beijing geriatric medical center: emphasizing the blaKPC-2 carrying high-risk clones and their spread
Authors: Ge Xin , Zhou Yu , Jin Hang , Liu Kangkang , Zhu Kunpeng , Yu Yulong , Xue Jingzhuang , Wang Qi , Du Xinying , Wang Hui , Xiang Ying , Li Wenjun , Tian Sai , Yan Zhongqiang , Qiu Shaofu
Published: February 2024

Background

The escalating resistance of Klebsiella pneumoniae, a prevalent pathogen in healthcare settings, especially its carbapenem-resistant K. pneumoniae (CRKP), to a wide array of antibiotics, notably β-lactams, constitutes a formidable challenge for healthcare and global public health management.

Methods

This research compared the resistance phenotypes and genomic profiles of CRKP and Non-CRKP isolates in a Beijing hospital, focusing on high-risk blaKPC-2 gene-bearing CRKP clones and the structure of mobile genetic elements facilitating their spread across hospital departments. Forty K. pneumoniae isolates were collected from various departments of the hospital and subjected to antimicrobial susceptibility testing and whole-genome sequencing to analyze their resistance phenotypes and genomic features.

Results

The study revealed that among the 31 CRKP isolates, ST11 is the most common sequence type, with K47 and OL101 being the dominant capsule types, primarily observed in the respiratory department. In terms of antimicrobial susceptibility: 87.5% of the isolates exhibited multidrug resistance (MDR), with a high resistance rate of 30% against tigecycline. All CRKP isolates demonstrated resistance to multiple drug classes (≥5 CLSI classes). Non-CRKP isolates also showed high resistance rates to minocycline and doxycycline (77.8%). the ST11-KL47-OL101 type emerged as the predominant clone among the CRKP isolates carrying the blaKPC-2 gene. This dominance appears to be mediated by the pKpnR03_2 plasmid, which harbors not only blaKPC-2 and rmtb but also gene clusters pertinent to iron transport and arsenic resistance. These isolates, clustering in the C3 clade of the phylogenetic tree, exhibited minor genetic variations and close evolutionary relationships, suggesting a plasmid-driven spread across various hospital departments.

Conclusion

In summary, our study highlights the extensive spread of antibiotic-resistant K. pneumoniae across various departments in our hospital, with a particular emphasis on the dominant clonal proliferation of the ST11-KL47-OL101 CRKP strain. This finding underscores the significant role of plasmid-mediated gene transfer in the evolution and dissemination of resistant strains within hospital environments. The study emphasizes the necessity for ongoing surveillance of antibiotic resistance and genomic analysis in hospital settings to effectively monitor and manage these challenges.
Microglial activation in spaceflight and microgravity: potential risk of cognitive dysfunction and poor neural health
Authors: Li Zihan , Wu Jiarui , Zhao Tianyuan , Wei Yiyun , Xu Yajing , Liu Zongjian , Li Xiaoqiong , Chen Xuechai
Published: February 2024

Due to the increased crewed spaceflights in recent years, it is vital to understand how the space environment affects human health. A lack of gravitational force is known to risk multiple physiological functions of astronauts, particularly damage to the central nervous system (CNS). As innate immune cells of the CNS, microglia can transition from a quiescent state to a pathological state, releasing pro-inflammatory cytokines that contribute to neuroinflammation. There are reports indicating that microglia can be activated by simulating microgravity or exposure to galactic cosmic rays (GCR). Consequently, microglia may play a role in the development of neuroinflammation during spaceflight. Prolonged spaceflight sessions raise concerns about the chronic activation of microglia, which could give rise to various neurological disorders, posing concealed risks to the neural health of astronauts. This review summarizes the risks associated with neural health owing to microglial activation and explores the stressors that trigger microglial activation in the space environment. These stressors include GCR, microgravity, and exposure to isolation and stress. Of particular focus is the activation of microglia under microgravity conditions, along with the proposal of a potential mechanism.
Fluorescence microscopy shadow imaging for neuroscience
Authors: Inavalli V. V. G. Krishna , Puente Muñoz Virginia , Draffin Jonathan E. , Tønnesen Jan
Published: February 2024

Fluorescence microscopy remains one of the single most widely applied experimental approaches in neuroscience and beyond and is continuously evolving to make it easier and more versatile. The success of the approach is based on synergistic developments in imaging technologies and fluorophore labeling strategies that have allowed it to greatly diversify and be used across preparations for addressing structure as well as function. Yet, while targeted labeling strategies are a key strength of fluorescence microscopy, they reciprocally impose general limitations on the possible types of experiments and analyses. One recent development that overcomes some of these limitations is fluorescence microscopy shadow imaging, where membrane-bound cellular structures remain unlabeled while the surrounding extracellular space is made to fluoresce to provide a negative contrast shadow image. When based on super-resolution STED microscopy, the technique in effect provides a positive image of the extracellular space geometry and entire neuropil in the field of view. Other noteworthy advantages include the near elimination of the adverse effects of photobleaching and toxicity in live imaging, exhaustive and homogeneous labeling across the preparation, and the ability to apply and adjust the label intensity on the fly. Shadow imaging is gaining popularity and has been applied on its own or combined with conventional positive labeling to visualize cells and synaptic proteins in their parenchymal context. Here, we highlight the inherent limitations of fluorescence microscopy and conventional labeling and contrast these against the pros and cons of recent shadow imaging approaches. Our aim is to describe the brief history and current trajectory of the shadow imaging technique in the neuroscience field, and to draw attention to its ease of application and versatility.
Identifying clinical phenotypes of frontotemporal dementia in post-9/11 era veterans using natural language processing
Authors: Panahi Samin , Mayo Jamie , Kennedy Eamonn , Christensen Lee , Kamineni Sreekanth , Sagiraju Hari Krishna Raju , Cooper Tyler , Tate David F. , Rupper Randall , Pugh Mary Jo
Published: February 2024

Introduction

Frontotemporal dementia (FTD) encompasses a clinically and pathologically diverse group of neurodegenerative disorders, yet little work has quantified the unique phenotypic clinical presentations of FTD among post-9/11 era veterans. To identify phenotypes of FTD using natural language processing (NLP) aided medical chart reviews of post-9/11 era U.S. military Veterans diagnosed with FTD in Veterans Health Administration care.

Methods

A medical record chart review of clinician/provider notes was conducted using a Natural Language Processing (NLP) tool, which extracted features related to cognitive dysfunction. NLP features were further organized into seven Research Domain Criteria Initiative (RDoC) domains, which were clustered to identify distinct phenotypes.

Results

Veterans with FTD were more likely to have notes that reflected the RDoC domains, with cognitive and positive valence domains showing the greatest difference across groups. Clustering of domains identified three symptom phenotypes agnostic to time of an individual having FTD, categorized as Low (16.4%), Moderate (69.2%), and High (14.5%) distress. Comparison across distress groups showed significant differences in physical and psychological characteristics, particularly prior history of head injury, insomnia, cardiac issues, anxiety, and alcohol misuse. The clustering result within the FTD group demonstrated a phenotype variant that exhibited a combination of language and behavioral symptoms. This phenotype presented with manifestations indicative of both language-related impairments and behavioral changes, showcasing the coexistence of features from both domains within the same individual.

Discussion

This study suggests FTD also presents across a continuum of severity and symptom distress, both within and across variants. The intensity of distress evident in clinical notes tends to cluster with more co-occurring conditions. This examination of phenotypic heterogeneity in clinical notes indicates that sensitivity to FTD diagnosis may be correlated to overall symptom distress, and future work incorporating NLP and phenotyping may help promote strategies for early detection of FTD.
Emerging biomarkers for improving pregnancy planning in multiple sclerosis
Authors: Cuello Juan Pablo , Meldaña Rivera Ariana , Monreal Enric , Gómez Lozano Ana , García Cano Ana Maria , García Domínguez Jose Manuel , Fernández Velasco José Ignacio , Costa-Frossard França Lucienne , Goicochea Haydee , Higueras Yolanda , De León-Luis Juan Antonio , Sainz De La Maza Susana , Villarrubia Noelia , Arribas Gómez Ignacio , Ruiz Perez Irene , Martinez Ginés Maria Luisa , Villar Luisa María
Published: February 2024

Background

Patient disability, relapse rate, and age are used for family planning in multiple sclerosis (MS). However, the need for more accurate biomarkers is widely recognized. We aimed to explore the influence of age on neurofilament light chain (sNfL), which reflects acute inflammation; glial fibrillary acidic protein (GFAP), associated with disability progression independent of relapses; and anti-Müllerian hormone (AMH), reflecting ovarian reserve, to provide a tailored family planning strategy.

Methods

This case-control study included 95 MS patients and 61 healthy control women (HCW). sNfL and GFAP levels were measured using a sensitive single-molecule array assay. AMH levels were measured by the automated Elecsys® Anti-Müllerian Hormone Assay.

Results

We observed no significant differences in AMH values between MS patients and the control group within any of the age-matched categories. Age exhibited a negative correlation with AMH values in both groups, as expected. Nevertheless, our findings suggest a slight tendency toward reduced ovarian reserve in MS patients (rho MS patients = −0.67, p < 0.0001; rho HCW = −0.43, p = 0.0006). Interestingly, among the 76 MS participants under 40 years old, we identified ten individuals (13.1%) with AMH levels below 0.7 ng/ml, indicative of a low ovarian reserve, and an additional six individuals (7.8%) with AMH levels between 0.7 ng/ml and 0.9 ng/ml, suggesting a potential risk of premature ovarian failure. Conversely, sNfL and GFAP levels in the MS group exhibited high variability but showed no significant association with age intervals.

Conclusion

We found no significant differences in AMH, sNfL or GFAP values between MS patients and the control group within any of the age-matched categories. The assessment of AMH, sNFL and GFAP levels at MS onset facilitates personalized therapeutic and family planning strategies for childbearing-age women.
Liquid chromatography coupled to mass spectrometry metabolomic analysis of cerebrospinal fluid revealed the metabolic characteristics of moyamoya disease
Authors: Yu Jin , Chen Tongyu , Li Xiang , Chen Jincao , Wei Wei , Zhang Jianjian
Published: February 2024

Objective

Metabolomics has found extensive applications in the field of neurological diseases, significantly contributing to their diagnosis and treatment. However, there has been limited research applying metabolomics to moyamoya disease (MMD). This study aims to investigate and identify differential metabolites associated with MMD.

Methods

We employed a liquid chromatography coupled with mass spectrometry (LC-MS) approach, complemented by univariate and multivariate analyses, to discern metabolic biomarkers in cerebrospinal fluid samples. We then compared these biomarkers between MMD patients and healthy controls (Ctl).

Results

Sixteen patients diagnosed with MMD via cerebral angiography and eight healthy controls were enrolled in this study. Comparative analyses, including univariate and multivariate analyses, correlation studies, heatmaps, Volcano Plots, and KEGG pathway enrichment, were performed between MMD patients and controls. As a result, we identified 129 significant differential metabolites in the cerebrospinal fluid between MMD patients and controls. These metabolic biomarkers are associated with various pathways, with notable involvement in purine and pyrimidine metabolism.

Conclusion

Utilizing an LC-MS-based metabolomics approach holds promise for enhancing the clinical diagnosis of MMD. The identified biomarkers offer potential avenues for the development of novel diagnostic methods for MMD and offer fresh insights into the pathogenesis of the disease.
Factors associated with older adults’ cognitive decline 6 months after gamma-variant SARS-CoV-2 infection
Authors: Peixoto Vanessa Giffoni M. N. P. , Facci Lucas Alves , Barbalho Thiago C. S. , Souza Raíssa Nascimento , Duarte Alice Mendes , dos Santos Marina Bruxel , Almondes Katie Moraes
Published: February 2024

Background

Cognitive deficits are commonly reported after COVID-19 recovery, but little is known in the older population. This study aims to investigate possible cognitive damage in older adults 6 months after contracting COVID-19, as well as individual risk factors.

Methods

This cross-sectional study involved 70 participants aged 60–78 with COVID-19 6 months prior and 153 healthy controls. Montreal Cognitive Assessment—Basic (MoCA-B) screened for cognitive impairment; Geriatric Depression Scale and Geriatric Anxiety Inventory screened for depression and anxiety. Data were collected on demographics and self-reports of comorbid conditions.

Results

The mean age of participants was 66.97 ± 4.64 years. A higher proportion of individuals in the COVID group complained about cognitive deficits (χ2 = 3.574; p = 0.029) and presented with deficient MoCA-B scores (χ2 = 6.098, p = 0.014) compared to controls. After controlling for multiple variables, all the following factors resulted in greater odds of a deficient MoCA-B: COVID-19 6-months prior (OR, 2.44; p = 0.018), age (OR, 1.15; p < 0.001), lower income (OR, 0.36; p = 0.070), and overweight (OR, 2.83; p = 0.013). Further analysis pointed to individual characteristics in COVID-19-affected patients that could explain the severity of the cognitive decline: age (p = 0.015), lower income (p < 0.001), anxiety (p = 0.049), ageusia (p = 0.054), overweight (p < 0.001), and absence of cognitively stimulating activities (p = 0.062).

Conclusion

Our study highlights a profile of cognitive risk aggravation over aging after COVID-19 infection, which is likely mitigated by wealth but worsened in the presence of overweight. Ageusia at the time of acute COVID-19, anxiety, being overweight, and absence of routine intellectual activities are risk factors for more prominent cognitive decline among those infected by COVID-19.
Digital neuropsychological measures by defense automated neurocognitive assessment: reference values and clinical correlates
Authors: Ding Huitong , Kim Minzae , Searls Edward , Sunderaraman Preeti , De Anda-Duran Ileana , Low Spencer , Popp Zachary , Hwang Phillip H. , Li Zexu , Goyal Kriti , Hathaway Lindsay , Monteverde Jose , Rahman Salman , Igwe Akwaugo , Kolachalama Vijaya B. , Au Rhoda , Lin Honghuang
Published: February 2024

Introduction

Although the growth of digital tools for cognitive health assessment, there’s a lack of known reference values and clinical implications for these digital methods. This study aims to establish reference values for digital neuropsychological measures obtained through the smartphone-based cognitive assessment application, Defense Automated Neurocognitive Assessment (DANA), and to identify clinical risk factors associated with these measures.

Methods

The sample included 932 cognitively intact participants from the Framingham Heart Study, who completed at least one DANA task. Participants were stratified into subgroups based on sex and three age groups. Reference values were established for digital cognitive assessments within each age group, divided by sex, at the 2.5th, 25th, 50th, 75th, and 97.5th percentile thresholds. To validate these values, 57 cognitively intact participants from Boston University Alzheimer’s Disease Research Center were included. Associations between 19 clinical risk factors and these digital neuropsychological measures were examined by a backward elimination strategy.

Results

Age- and sex-specific reference values were generated for three DANA tasks. Participants below 60 had median response times for the Go-No-Go task of 796 ms (men) and 823 ms (women), with age-related increases in both sexes. Validation cohort results mostly aligned with these references. Different tasks showed unique clinical correlations. For instance, response time in the Code Substitution task correlated positively with total cholesterol and diabetes, but negatively with high-density lipoprotein and low-density lipoprotein cholesterol levels, and triglycerides.

Discussion

This study established and validated reference values for digital neuropsychological measures of DANA in cognitively intact white participants, potentially improving their use in future clinical studies and practice.
Novel artificial intelligence-based hypodensity detection tool improves clinician identification of hypodensity on non-contrast computed tomography in stroke patients
Authors: Santos Angela Dos , Visser Milanka , Lin Longting , Bivard Andrew , Churilov Leonid , Parsons Mark William
Published: February 2024

Introduction

In acute stroke, identifying early changes (parenchymal hypodensity) on non-contrast CT (NCCT) can be challenging. We aimed to identify whether the accuracy of clinicians in detecting acute hypodensity in ischaemic stroke patients on a non-contrast CT is improved with the use of an Artificial Intelligence (AI) based, automated hypodensity detection algorithm (HDT) using MRI-DWI as the gold standard.

Methods

The study employed a case-crossover within-clinician design, where 32 clinicians were tasked with identifying hypodensity lesions on NCCT scans for five a priori selected patient cases, before and after viewing the AI-based HDT. The DICE similarity coefficient (DICE score) was the primary measure of accuracy. Statistical analysis compared DICE scores with and without AI-based HDT using mixed-effects linear regression, with individual NCCT scans and clinicians as nested random effects.

Results

The AI-based HDT had a mean DICE score of 0.62 for detecting hypodensity across all NCCT scans. Clinicians’ overall mean DICE score was 0.33 (SD 0.31) before AI-based HDT implementation and 0.40 (SD 0.27) after implementation. AI-based HDT use was associated with an increase of 0.07 (95% CI: 0.02–0.11, p = 0.003) in DICE score accounting for individual scan and clinician effects. For scans with small lesions, clinicians achieved a mean increase in DICE score of 0.08 (95% CI: 0.02, 0.13, p = 0.004) following AI-based HDT use. In a subgroup of 15 trainees, DICE score improved with AI-based HDT implementation [mean difference in DICE 0.09 (95% CI: 0.03, 0.14, p = 0.004)].

Discussion

AI-based automated hypodensity detection has potential to enhance clinician accuracy of detecting hypodensity in acute stroke diagnosis, especially for smaller lesions, and notably for less experienced clinicians.
Cilostazol-based dual antiplatelet treatment in ischemic stroke or transient ischemic attack patients with asymptomatic carotid artery disease: a propensity score matching analysis
Authors: Thiraworawong Thon , Pathonsmith Chadawan
Published: February 2024

Background

The optimal treatment for asymptomatic atherosclerotic carotid artery disease remains controversial. Data on the efficacy of antiplatelet agents and stroke outcomes are limited. This study aimed to examine the efficacy and safety of cilostazol-based dual antiplatelet therapy in patients with ischemic stroke or transient ischemic attack and asymptomatic carotid artery disease.

Methods

This retrospective cohort study was conducted in a tertiary-care setting and included baseline characteristics and clinical outcomes of participants. The study included patients who had experienced first-ever ischemic stroke or transient ischemic attack and asymptomatic atherosclerotic carotid artery stenosis, with a minimum follow-up period of 1 year. Asymptomatic carotid artery stenosis refers to stenosis in patients without neurological symptoms referable to the carotid arteries. Propensity scores were estimated using a logistic regression model based on participants’ baseline characteristics. The efficacy outcome was the composite outcome of recurrent ischemic events and vascular-related death in patients with ischemic stroke or transient ischemic attack and asymptomatic carotid artery stenosis. The safety outcome was the occurrence of hemorrhagic complications such as intracranial hemorrhages or extracranial hemorrhages. The effectiveness of dual therapy compared to monotherapy was evaluated at various time points following the initiation of antiplatelet treatment.

Results

This study included 516 patients with a 1-year follow-up period. At 1 year, composite events occurred in 10 (6.3%) patients in the dual antiplatelet group compared with 12 (7.6%) in the single antiplatelet group (HR, 0.74; 95% CI, 0.61–0.90; p = 0.024). Extracranial hemorrhage occurred in 12 (7.6%) patients in the dual antiplatelet group compared with nine (5.7%) in the single antiplatelet group (HR, 1.35; 95% CI, 1.13–1.48; p = 0.017). No intracranial hemorrhages were observed in this cohort.

Conclusion

Patients with asymptomatic carotid artery stenosis who received cilostazol-based dual antiplatelet therapy had a lower risk of composite events but a higher risk of minor extracranial hemorrhage than those who received a single antiplatelet agent.
Comparative efficacy of different repetitive transcranial magnetic stimulation protocols for lower extremity motor function in stroke patients: a network meta-analysis
Authors: Wang Chengshuo , Zhang Qin , Zhang Linli , Zhao Dongyan , Xu Yanan , Liu Zejian , Wu Chunli , Wu Shengzhu , Yong Mingjin , Wu Liang
Published: February 2024

Background

Lower extremity motor dysfunction is one of the most severe consequences after stroke, restricting functional mobility and impairing daily activities. Growing evidence suggests that repetitive transcranial magnetic stimulation (rTMS) can improve stroke patients’ lower extremity motor function. However, there is still controversy about the optimal rTMS protocol. Therefore, we compared and analyzed the effects of different rTMS protocols on lower extremity motor function in stroke patients using network meta-analysis (NMA).

Methods

We systematically searched CNKI, WanFang, VIP, CBM, PubMed, Embase, Web of Science, and Cochrane Library databases (from origin to 31 December 2023). Randomized controlled trials (RCTs) or crossover RCTs on rTMS improving lower extremity motor function in stroke patients were included. Two authors independently completed article screening, data extraction, and quality assessment. RevMan (version 5.4) and Stata (version 17.0) were used to analyze the data.

Results

A total of 38 studies with 2,022 patients were eligible for the NMA. The interventions included HFrTMS-M1, LFrTMS-M1, iTBS-Cerebellum, iTBS-M1, dTMS-M1, and Placebo. The results of NMA showed that LFrTMS-M1 ranked first in FMA-LE and speed, and HFrTMS-M1 ranked first in BBS, TUGT, and MEP amplitude. The subgroup analysis of FMA-LE showed that HFrTMS-M1 was the best stimulation protocol for post-stroke time > 1 month, and LFrTMS-M1 was the best stimulation protocol for post-stroke time ≤ 1 month.

Conclusion

Considering the impact of the stroke phase on the lower extremity motor function, the current research evidence shows that HFrTMS-M1 may be the preferred stimulation protocol to improve the lower extremity motor function of patients for post-stroke time > 1 month, and LFrTMS-M1 for post-stroke time ≤ 1 month. However, the above conclusion needs further analysis and validation by more high-quality RCTs.

Systematic Review Registration:www.crd.york.ac.uk/prospero/, identifier (CRD42023474215).
Sleep, inflammation, and hemodynamics in rodent models of traumatic brain injury
Authors: Green Tabitha R. F. , Carey Sean D. , Mannino Grant , Craig John A. , Rowe Rachel K. , Zielinski Mark R.
Published: February 2024

Traumatic brain injury (TBI) can induce dysregulation of sleep. Sleep disturbances include hypersomnia and hyposomnia, sleep fragmentation, difficulty falling asleep, and altered electroencephalograms. TBI results in inflammation and altered hemodynamics, such as changes in blood brain barrier permeability and cerebral blood flow. Both inflammation and altered hemodynamics, which are known sleep regulators, contribute to sleep impairments post-TBI. TBIs are heterogenous in cause and biomechanics, which leads to different molecular and symptomatic outcomes. Animal models of TBI have been developed to model the heterogeneity of TBIs observed in the clinic. This review discusses the intricate relationship between sleep, inflammation, and hemodynamics in pre-clinical rodent models of TBI.
Object-oriented hand dexterity and grasping abilities, from the animal quarters to the neurosurgical OR: a systematic review of the underlying neural correlates in non-human, human primate and recent findings in awake brain surgery
Authors: Tariciotti Leonardo , Mattioli Luca , Viganò Luca , Gallo Matteo , Gambaretti Matteo , Sciortino Tommaso , Gay Lorenzo , Conti Nibali Marco , Gallotti Alberto , Cerri Gabriella , Bello Lorenzo , Rossi Marco
Published: February 2024

Introduction

The sensorimotor integrations subserving object-oriented manipulative actions have been extensively investigated in non-human primates via direct approaches, as intracortical micro-stimulation (ICMS), cytoarchitectonic analysis and anatomical tracers. However, the understanding of the mechanisms underlying complex motor behaviors is yet to be fully integrated in brain mapping paradigms and the consistency of these findings with intraoperative data obtained during awake neurosurgical procedures for brain tumor removal is still largely unexplored. Accordingly, there is a paucity of systematic studies reviewing the cross-species analogies in neural activities during object-oriented hand motor tasks in primates and investigating the concordance with intraoperative findings during brain mapping. The current systematic review was designed to summarize the cortical and subcortical neural correlates of object-oriented fine hand actions, as revealed by fMRI and PET studies, in non-human and human primates and how those were translated into neurosurgical studies testing dexterous hand-movements during intraoperative brain mapping.

Methods

A systematic literature review was conducted following the PRISMA guidelines. PubMed, EMBASE and Web of Science databases were searched. Original articles were included if they: (1) investigated cortical activation sites on fMRI and/or PET during grasping task; (2) included humans or non-human primates. A second query was designed on the databases above to collect studies reporting motor, hand manipulation and dexterity tasks for intraoperative brain mapping in patients undergoing awake brain surgery for any condition. Due to the heterogeneity in neurosurgical applications, a qualitative synthesis was deemed more appropriate.

Results

We provided an updated overview of the current state of the art in translational neuroscience about the extended frontoparietal grasping-praxis network with a specific focus on the comparative functioning in non-human primates, healthy humans and how the latter knowledge has been implemented in the neurosurgical operating room during brain tumor resection.

Discussion

The anatomical and functional correlates we reviewed confirmed the evolutionary continuum from monkeys to humans, allowing a cautious but practical adoption of such evidence in intraoperative brain mapping protocols. Integrating the previous results in the surgical practice helps preserve complex motor abilities, prevent long-term disability and poor quality of life and allow the maximal safe resection of intrinsic brain tumors.
Multi-modal ultrasound multistage classification of PTC cervical lymph node metastasis via DualSwinThyroid
Authors: Liu Qiong , Li Yue , Hao Yanhong , Fan Wenwen , Liu Jingjing , Li Ting , Liu Liping
Published: February 2024

Objective

This study aims to predict cervical lymph node metastasis in papillary thyroid carcinoma (PTC) patients with high accuracy. To achieve this, we introduce a novel deep learning model, DualSwinThyroid, leveraging multi-modal ultrasound imaging data for prediction.

Materials and methods

We assembled a substantial dataset consisting of 3652 multi-modal ultrasound images from 299 PTC patients in this retrospective study. The newly developed DualSwinThyroid model integrates various ultrasound modalities and clinical data. Following its creation, we rigorously assessed the model’s performance against a separate testing set, comparing it with established machine learning models and previous deep learning approaches.

Results

Demonstrating remarkable precision, DualSwinThyroid achieved an AUC of 0.924 and an 96.3% accuracy on the test set. The model efficiently processed multi-modal data, pinpointing features indicative of lymph node metastasis in thyroid nodule ultrasound images. It offers a three-tier classification that aligns each level with a specific surgical strategy for PTC treatment.

Conclusion

DualSwinThyroid, a deep learning model designed with multi-modal ultrasound radiomics, effectively estimates the degree of cervical lymph node metastasis in PTC patients. In addition, it also provides early, precise identification and facilitation of interventions for high-risk groups, thereby enhancing the strategic selection of surgical approaches in managing PTC patients.
Vernal keratoconjunctivitis in adults: a narrative review of prevalence, pathogenesis, and management
Authors: Di Zazzo Antonio , Zhu Angela Y. , Nischal Ken , Fung Simon S. M.
Published: February 2024

Vernal keratoconjunctivitis (VKC) is a chronic, progressive, allergic ocular surface disorder that can lead to sight-threatening complications. VKC occurs primarily in children and generally resolves about the time of puberty; however, case series and retrospective analyses indicate that approximately 10% of patients with VKC are adults, and that a subset of adult cases develop after puberty. Consequently, two age-related variants of VKC have recently been described: early-onset VKC—which manifests during childhood and persists into adult life—and late-onset disease, which emerges de novo after puberty. Although the signs and symptoms of adult and childhood VKC are similar, adult VKC is a long-lasting disease characterized by severe inflammation and increased risk of conjunctival fibrosis, which may place adult patients at higher risk for sight-threatening complications and adverse impacts on daily life. This review discusses the epidemiology, signs, symptoms, immunopathogenesis of adult VKC variants, and highlights current gaps in research and management of patients with this condition.
The effectiveness of oral anti-SARS-CoV-2 agents in non-hospitalized COVID-19 patients with nonalcoholic fatty liver disease: a retrospective study
Authors: Yang Chun-Chi , Tsai Ya-Wen , Wang Su-Hung , Wu Jheng-Yan , Liu Ting-Hui , Hsu Wan-Hsuan , Huang Po-Yu , Chuang Min-Hsiang , Sheu Ming-Jen , Lai Chih-Cheng
Published: February 2024

Background: The effectiveness of the novel oral antiviral agents, nirmatrelvir plus ritonavir and molnupiravir, in treating COVID-19 in patients with nonalcoholic fatty liver disease is unclear.

Objective: To assess the effectiveness of novel oral antiviral agents against COVID-19 among patients with nonalcoholic fatty liver diseases.

Methods: This retrospective cohort study used the TriNetX Research Network to identify non-hospitalized patients with COVID-19 and nonalcoholic fatty liver disease between 1 January 2022, and 30 June 2023. Propensity score matching was used to form two matched cohorts treated with or without nirmatrelvir-ritonavir or molnupiravir.

Results: In the two matched cohorts of 6,358 patients each, the use of novel oral antiviral agents was associated with a significantly lower risk of all-cause emergency department visits, hospitalization, or mortality (6.59% versus 8.24%; hazard ratio [HR], 0.80; 95% confidence interval [CI], 0.70–0.91). The novel antiviral group had a significantly lower risk of all-cause emergency department visits (HR, 0.85; 95% CI, 0.74–0.99). Additionally, the incidence of hospitalization was significantly lower in the oral antiviral group than in the control group (HR, 0.71; 95% CI, 0.55–0.90). There were no deaths in the oral antiviral group but 12 deaths in the control group.

Conclusion: Novel oral antiviral agents are beneficial for treating COVID-19 in patients with nonalcoholic fatty liver disease.
Knockdown of ANGPTL2 promotes left ventricular systolic dysfunction by upregulation of NOX4 in mice
Authors: Labbé Pauline , Martel Cécile , Shi Yan-Fen , Montezano Augusto , He Ying , Gillis Marc-Antoine , Higgins Marie-Ève , Villeneuve Louis , Touyz Rhian , Tardif Jean-Claude , Thorin-Trescases Nathalie , Thorin Eric
Published: February 2024

Background: Angiopoietin-like 2 (ANGPTL2) is a pro-inflammatory and pro-oxidant circulating protein that predicts and promotes chronic inflammatory diseases such as atherosclerosis in humans. Transgenic murine models demonstrated the deleterious role of ANGPTL2 in vascular diseases, while deletion of ANGPTL2 was protective. The nature of its role in cardiac tissues is, however, less clear. Indeed, in adult mice knocked down (KD) for ANGPTL2, we recently reported a mild left ventricular (LV) dysfunction originating from a congenital aortic valve stenosis, demonstrating that ANGPTL2 is essential to cardiac development and function.

Hypothesis: Because we originally demonstrated that the KD of ANGPTL2 protected vascular endothelial function via an upregulation of arterial NOX4, promoting the beneficial production of dilatory H2O2, we tested the hypothesis that increased cardiac NOX4 could negatively affect cardiac redox and remodeling and contribute to LV dysfunction observed in adult Angptl2-KD mice.

Methods and results: Cardiac expression and activity of NOX4 were higher in KD mice, promoting higher levels of cardiac H2O2 when compared to wild-type (WT) mice. Immunofluorescence showed that ANGPTL2 and NOX4 were co-expressed in cardiac cells from WT mice and both proteins co-immunoprecipitated in HEK293 cells, suggesting that ANGPTL2 and NOX4 physically interact. Pressure overload induced by transverse aortic constriction surgery (TAC) promoted LV systolic dysfunction in WT mice but did not further exacerbate the dysfunction in KD mice. Importantly, the severity of LV systolic dysfunction in KD mice (TAC and control SHAM) correlated with cardiac Nox4 expression. Injection of an adeno-associated virus (AAV9) delivering shRNA targeting cardiac Nox4 expression fully reversed LV systolic dysfunction in KD-SHAM mice, demonstrating the causal role of NOX4 in cardiac dysfunction in KD mice. Targeting cardiac Nox4 expression in KD mice also induced an antioxidant response characterized by increased expression of NRF2/KEAP1 and catalase.

Conclusion: Together, these data reveal that the absence of ANGPTL2 induces an upregulation of cardiac NOX4 that contributes to oxidative stress and LV dysfunction. By interacting and repressing cardiac NOX4, ANGPTL2 could play a new beneficial role in the maintenance of cardiac redox homeostasis and function.
Volume loss during muscle reinnervation surgery is correlated with reduced CMAP amplitude but not reduced force output in a rat hindlimb model
Authors: Lowe Alexis L. , Rivera Santana Maria V. , Bopp Taylor , Quinn Kiara N. , Johnson Johnnie , Ward Christopher , Chung Tae Hwan , Tuffaha Sami , Thakor Nitish V.
Published: February 2024

Introduction: Muscle reinnervation (MR) surgery offers rehabilitative benefits to amputees by taking severely damaged nerves and providing them with new denervated muscle targets (DMTs). However, the influence of physical changes to muscle tissue during MR surgery on long-term functional outcomes remains understudied.

Methods: Our rat hindlimb model of MR surgery utilizes vascularized, directly neurotized DMTs made from the lateral gastrocnemius (LG), which we employed to assess the impact of muscle tissue size on reinnervation outcomes, specifically pairing the DMT with the transected peroneal nerve. We conducted MR surgery with both DMTs at full volume and DMTs with partial volume loss of 500 mg at the time of surgery (n = 6 per group) and measured functional outcomes after 100 days of reinnervation. Compound motor action potentials (CMAPs) and isometric tetanic force production was recorded from reinnervated DMTs and compared to contralateral naïve LG muscles as positive controls.

Results: Reinnervated DMTs consistently exhibited lower mass than positive controls, while DMTs with partial volume loss showed no significant mass reduction compared to full volume DMTs (p = 0.872). CMAP amplitudes were lower on average in reinnervated DMTs, but a broad linear correlation also exists between muscle mass and maximum CMAP amplitude irrespective of surgical group (R2 = 0.495). Surprisingly, neither MR group, with or without volume loss, demonstrated decreased force compared to positive controls. The average force output of reinnervated DMTs, as a fraction of the contralateral LG’s force output, approached 100% for both MR groups, a notable deviation from the 9.6% (±6.3%) force output observed in our negative control group at 7 days post-surgery. Tissue histology analysis revealed few significant differences except for a marked decrease in average muscle fiber area of reinnervated DMTs with volume loss compared to positive controls (p = 0.001).

Discussion: The results from our rat model of MR suggests that tissue electrophysiology (CMAPs) and kinesiology (force production) may recover on different time scales, with volumetric muscle loss at the time of MR surgery not significantly reducing functional outcome measurements for the DMTs after 100 days of reinnervation.
Growth-regulating factor 15-mediated vascular cambium differentiation positively regulates wood formation in hybrid poplar (Populus alba × P. glandulosa)
Authors: Zhou Houjun , Song Xueqin , Lu Meng-Zhu
Published: February 2024

Introduction

Hybrid poplars are industrial trees in China. An understanding of the molecular mechanism underlying wood formation in hybrid poplars is necessary for molecular breeding. Although the division and differentiation of vascular cambial cells is important for secondary growth and wood formation, the regulation of this process is largely unclear.

Methods

In this study, mPagGRF15 OE and PagGRF15-SRDX transgenic poplars were generated to investigate the function of PagGRF15. RNA-seq and qRT-PCR were conducted to analyze genome-wide gene expression, while ChIP‒seq and ChIP-PCR were used to identified the downstream genes regulated by PagGRF15.

Results and discussion

We report that PagGRF15 from hybrid poplar (Populus alba × P. glandulosa), a growth-regulating factor, plays a critical role in the regulation of vascular cambium activity. PagGRF15 was expressed predominantly in the cambial zone of vascular tissue. Overexpression of mPagGRF15 (the mutated version of GRF15 in the miR396 target sequence) in Populus led to decreased plant height and internode number. Further stem cross sections showed that the mPagGRF15 OE plants exhibited significant changes in vascular pattern with an increase in xylem and a reduction in phloem. In addition, cambium cell files were decreased in the mPagGRF15 OE plants. However, dominant suppression of the downstream genes of PagGRF15 using PagGRF15-SRDX showed an opposite phenotype. Based on the RNA-seq and ChIP-seq results, combining qRT-PCR and ChIP-PCR analysis, candidate genes, such as WOX4b, PXY and GID1.3, were obtained and found to be mainly involved in cambial activity and xylem differentiation. Accordingly, we speculated that PagGRF15 functions as a positive regulator mediating xylem differentiation by repressing the expression of the WOX4a and PXY genes to set the pace of cambial activity. In contrast, PagGRF15 mediated the GA signaling pathway by upregulating GID1.3 expression to stimulate xylem differentiation. This study provides valuable information for further studies on vascular cambium differentiation mechanisms and genetic improvement of the specific gravity of wood in hybrid poplars.
Changes in free amino acid and protein polymerization in wheat caryopsis and endosperm during filling after shading
Authors: Ma Hongliang , Yang Yongheng , Wu Dongming , Xiang Gang , Luo Ting , Huang Xiulan , Yang Hongkun , Zheng Ting , Fan Gaoqiong
Published: February 2024

Over the past several decades, a decreasing trend in solar radiation has been observed during the wheat growing season. The effects of shade stress on grain yield formation have been extensively studied. However, little information on shade stress’s effects on protein formation warrants further investigation. Two wheat cultivars were grown under three treatments, no shade as the control group (CK), shading from the joint to the anthesis stage (S1), and shading from the joint to the mature stage (S2), to investigate the effects of shade stress on the free amino acids of the caryopsis and endosperm and protein accumulation during grain filling. The dry mass of caryopsis and endosperm was significantly decreased under shade stress, whereas Glu, Ser, Ala, and Asp and protein relative content increased during grain filling. The observed increases in total protein in S1 and S2 were attributed to the increases in the SDS-isoluble and SDS-soluble protein extracts, respectively. S1 improved polymer protein formation, but S2 delayed the conversion of albumins and globulins into monomeric and polymeric proteins. Moreover, shade stress increased the proportion of SDS-unextractable polymeric protein, which represented an increase in the degree of protein polymerization. The polymerization of protein interrelations between protein components and accumulation in caryopsis and endosperm provided novel insights into wheat quality formation under shade stress.
ASEAN cooperation to combat transnational crime: progress, perils, and prospects
Authors: Sundram Pushpanathan
Published: February 2024

The Association of Southeast Asian Nations (ASEAN) has grappled with the persistent threat of transnational crime (TC) in Southeast Asia since its establishment in 1967. The rising tide of globalization and technological advancement has only exacerbated the problem, leading to the evolution and organization of various criminal activities. As ASEAN faces a multitude of non-traditional security challenges that transcend national borders, including climate change, infectious diseases, and resource scarcity, TC remains a critical concern that could jeopardize regional stability and security. This article undertakes an extensive analysis of ASEAN's endeavors to combat TC. It delves into key documents outlining ASEAN's commitment, highlights the significant achievements, and identifies the challenges facing the region. The qualitative study evaluates the effectiveness of ASEAN's response to TC within its cooperative framework and core principles. Through content analysis, it draws insights from ASEAN's official documents, as well as reports from Interpol and the United Nations Office on Drugs and Crime, to understand the regional efforts in countering TC. The research reveals a range of collaborative efforts initiated by ASEAN to tackle TC. By focusing on examples of successful operations, such as Operation Maharlika III against human trafficking and Operation HAECHI-I targeting cybercrime, the study underscores the vital role of cross-border cooperation. However, the analysis highlights the challenges posed by the complex nature of TC and the varying capabilities of ASEAN member states. It underscores the importance of regional cooperation and external partnerships to address the evolving threats of TC effectively. In essence, ASEAN's commitment to combating TC is evident through the adoption of strategic documents, joint operations, and capacity-building initiatives. Nevertheless, the evolving nature of TC and its diverse manifestations pose ongoing challenges. A balanced approach in addressing TC is needed that encompasses not only securitization but also a criminal justice response.
School characteristics and pupils’ thoughts of leaving upper secondary school: The INSchool project
Authors: Torland Emilie Aas , Karlstad Cecilie , Thørrisen Mikkel Magnus , Bonsaksen Tore , Haslerud Sturla Inge , Aas Randi Wågø
Published: February 2024

Introduction

Understanding pupils’ thoughts about leaving school may contribute to better identify those at risk of dropping out. Thus, we explored the associations between perceived psychological demands, decision control, and social support from teacher and fellow pupils, and pupils’ thoughts about leaving upper secondary school.

Methods

Cross-sectional data from a convenience non-probability sample of 249 pupils from 12 Norwegian upper secondary schools were collected using a school-modified version of the work-focused Job Content Questionnaire (JCQ). Adjusted logistic regression was used to analyze the data.

Results

Pupils who experienced higher psychological demands and lower social support from fellow pupils were more likely to experience thoughts of leaving school compared to those who experienced lower demands and high levels of social support. Decision control was not significantly associated with thoughts about leaving school.

Conclusion

High psychological demands may increase the likelihood of considering leaving school. Peer support can lessen such thoughts. Implication: Identifying whether pupils are thinking about leaving school can help identify those who are at risk of dropping out of upper secondary school.
Gaining masculine power through guns? The impact of masculinity threat on attitudes toward guns
Authors: Kachel Sven , Bloch Tibor , Bosson Jennifer K. , Lorenz Lea L. , Steffens Melanie C.
Published: February 2024

Gun violence is a serious problem in the United States and elsewhere and more so among men than women. We conducted an experiment to examine if men whose masculinity was threatened are more attracted to guns than non-threatened men, presumably to compensate for the threat. After completing a gender knowledge test, men (N = 168) randomly received either false masculinity threatening (experimental condition) or masculinity affirming (control condition) feedback. Subsequently, we measured men’s attitudes toward guns and their choice of a gun-range voucher. Men whose masculinity was threatened (vs. affirmed) showed more positive attitudes toward guns and were more likely to choose the voucher. Both effects were statistically significant when the whole sample was analyzed and when very strict exclusion criteria were applied. However, when data exclusions were based on a suspicion check, effects were statistically significant only when a covariate was included (i.e., social dominance orientation, patriotism, or experience with guns). We discuss reasons for this mixed evidence, including the possibility that suspicion regarding the masculinity feedback could itself be a compensatory reaction to threat.