bluuebunny/crossref_metadata_2025 huggingface dataset:
Précis of Thinking and Perceiving
Authors: Stokes Dustin R.
Published: July 2023

Thinking and Perceiving defends the claim that thought not only affects perceiving, thought improves perceiving. It thus defends a malleable architecture of the mind, opposite strong modularist views that claim that perception is informationally encapsulated and thus cognitively impenetrable. The argument for this view centers around cases of perceptual expertise. Experts in a wide variety of domains—radiology, birdwatching, elite athletics, fingerprint examination—have been empirically studied using behavioral, neural-physiological, and computational methods. This convergence of evidence is best explained in terms of cognitively sensitive perceptual improvements. And these improvements amount to epistemic virtue, where the virtue is partly resident in perception and credited to the perceiving agent. The view has far-reaching implications for a wide range of issues, including the epistemology of perception, the contents of perception, theory-ladenness in science and social perception, understanding and self-understanding, and aesthetic taste.
How radical is perceptual malleability? A reply to commentators
Authors: Stokes Dustin R.
Published: July 2023

The unifying theme across all four commentaries is the question: just how radical are the ideas contained in, and implied by, Thinking and Perceiving? Does the abandonment of the modularity of mind, and an embrace of the malleability of mind, have wide reaching consequences for empirical studies of sensory perception, for cognitive architecture, for the metaphysics of mind and the epistemology of perception? And which of those consequences are welcomed, and which of those are problematic? These general questions anchor in (at least) the following topics: learning and the role of cognition, object recognition, perceptual expertise, early versus late vision, perception and truth, virtue epistemology, and computational architectures of mind. This reply attempts to address the overarching question from this variety of angles taken in the four commentaries.
The distribution of hepatitis C viral genotypes shifted among chronic hepatitis C patients in Yunnan, China, between 2008–2018
Authors: Jia Yuanyuan , Zou Xiu , Yue Wei , Liu Jin , Yue Ming , Liu Yang , Liu Li , Huang Peng , Feng Yue , Xia Xueshan
Published: July 2023

Object

The hepatitis C virus (HCV) is prevalent across China, with a distinctive genotypic distribution that varies by geographical region and mode of transmission. Yunnan is one such geographical region wherein the local population continues to experience a high level of HCV infection, severely straining public health resources. This high prevalence is likely due to the increased incidence of intravenous drug use in that region, as Yunnan is a major point of entry for illegal heroin into China.

Methods

We investigated 510 individuals with chronic HCV infections in Yunnan Province from 2008 through 2018. Using reverse transcription PCR and Sanger sequencing to amplify and sequence samples. Bayesian analyses was performed to estimate the common ancestors and Bayesian skyline plot to estimate the effective viral population size. Molecular network was conducted to explore the characteristics of HCV transmission.

Results

We successfully amplified and sequenced a total of 503 viral samples and genotyped each as either 3b (37.6%), 3a (21.9%), 1b (19.3%), 2a (10.5%), HCV-6 (10.1%), or 1a (0.6%). Over this 11-year period, we observed that the proportion of 3a and 3b subtypes markedly increased and, concomitantly, that the proportion of 1b and 2a subtypes decreased. We also performed Bayesian analyses to estimate the common ancestors of the four major subtypes, 1b, 2a, 3a, and 3b. Finally, we determined that our Bayesian skyline plot and transmission network data correlated well with the changes we observed in the proportions of HCV subtypes over time.

Conclusions

Taken together, our results indicate that the prevalence of HCV 3a and 3b subtypes is rapidly increasing in Yunnan, thus demonstrating a steadily growing public health requirement to implement more stringent preventative and therapeutic measures to curb the spread of the virus.
Long-Term Performance Comparison of Bipolar Active vs. Quadripolar Passive Fixation Leads in Cardiac Resynchronisation Therapy
Authors: Schiedat Fabian , Bogossian Harilaos , Schöne Dominik , Aweimer Assem , Patsalis Polykarpos C. , Hanefeld Christoph , Mügge Andreas , Kloppe Axel
Published: July 2023

Background: Bipolar active fixation (BipolarAFL) and quadripolar passive fixation left-ventricular leads (QuadPFL) have been designed to reduce the risk of phrenic nerve stimulation (PNS), enable targeted left-ventricular pacing, and overcome problems of difficult coronary venous anatomy and lead dislodgment. This study sought to report the long-term safety and performance of a BipolarAFL, Medtronic Attain Stability 20066, compared to QuadPFL.

Methods: We performed a single-operator retrospective analysis of 81 patients receiving cardiac resynchronization therapy (CRT) (36 BipolarAFL, 45 QuadPFL). Immediate implant data and electrical and clinical data during follow-up (FU) were analyzed.

Results: BipolarAFL has been chosen in patients with significantly larger estimated vein diameter (at the lead tip: 7.2 ± 4.1 Fr vs. 4.1 ± 2.3 Fr, p < 0.001) without significant time difference until the final lead position was achieved (BipolarAFL: 20.9 ± 10.5 min, vs. QuadPFL: 18.9 ± 8.9 min, p = 0.35). At 12 month FU no difference in response rate to CRT was recorded between BipolarAFL and QuadPFL according to left ventricular end-systolic volume (61.1 vs. 60.0%, p = 0.82) and New York Heart Association (66.7 vs. 62.2%, p = 0.32). At median FU of 48 months (IQR: 44–54), no lead dislodgment occurred in both groups but a significantly higher proportion of PNS was recorded in QuadPFL (13 vs. 0%, p < 0.05). Electrical parameters were stable during FU in both groups without significant differences.

Conclusion: BipolarAFL can be implanted with ease in challenging coronary venous anatomy, shows excellent electrical performance and no difference in clinical outcome compared to QuadPFL.
Trends in computerized provider order entry: 20-year bibliometric overview
Authors: Gosselin Laura , Leguillon Romain , Rollin Laetitia , Lejeune Emeline , Darmoni Stéfan J. , Grosjean Julien
Published: July 2023

Background

Drug-related problems (DRPs) can lead to serious health issues and have significant economic impacts on healthcare systems. One solution to address this issue is the use of computerized physician order entry systems (CPOE), which can help prevent DRPs by reducing the risk of medication errors.

Objective

The purpose of this study is to provide an analysis on scientific production of the past 20 years in order to describe trends in academic publishing on CPOE and to identify the major topics as well as the predominant actors (journals, countries) involved in this field.

Methods

A PubMed search was carried out to extract articles related to computerized provider order entry during the period January 1st 2003– December 31st 2022 using a specific query. Data were downloaded from PubMed in Extensible Markup Language (XML) and were processed through a dedicated parser.

Results

A total of 2,946 articles were retrieved among 623 journals. One third of these articles were published in eight journals. Publications grew strongly from 2002 to 2006, with a dip in 2008 followed by an increase again in 2009. After 2009, there follows a decreasing until 2022.The most producing countries are the USA with 51.39% of the publication over the period by France (3.80%), and Canada (3.77%). About disciplines, the top 3 is: “medical informatics” (21.62% of articles), “pharmacy” (19.04%), and “pediatrics” (6.56%).

Discussion

This study provides an overview of publication trends related to CPOE, which exhibited a significant increase in the first decade of the 21st century followed by a decline after 2009. Possible reasons for this decline include the emergence of digital health tools beyond CPOE, as well as healthcare professionals experiencing alert fatigue of the current system.

Conclusion

Future research should focus on analyzing publication trends in the field of medical informatics and decision-making tools to identify other areas of interest that may have surpassed the development of CPOE.
Examining the relationship between anxiety and pathological demand avoidance in adults: a mixed methods approach
Authors: Johnson Matt , Saunderson Helen
Published: July 2023

Introduction

Pathological demand avoidance (PDA) is characterised by extreme avoidance of everyday demands. A recent study identified anxiety and intolerance of uncertainty (IU) as explanatory frameworks for understanding PDA in children, while anecdotal evidence suggests that anticipatory responses to uncertainty are also influential in the development and maintenance of PDA. Previous studies have relied upon parent-report of child representations of PDA; the lack of adult representation in the literature means that little can currently be said for how demand avoidance behaviours manifest in adulthood. The present study aimed to further an understanding of underlying mechanisms involved in the development and maintenance of PDA by recruiting a non-clinical adult cohort.

Methods

Experiment 1 utilised a correlational survey design in order to ascertain the extent to which MASQ-D30, IUS-12, and SBI scores could be used to predict EDA-QA scores (N = 163). In experiment 2, a subsample of participants from experiment 1 (n = 13) gave their experiential perspective on anxiety, uncertainty, and anticipation.

Results

Regression analysis found only MASQ-D30 and IUS-12 scores to significantly predict that of the EDA-QA. Additionally, interpretive phenomenological analysis of participant transcripts revealed four main themes (approach-avoidance behaviour, factors influencing anticipatory bias, vulnerability factors associated with demand avoidance, and development).

Discussion

Taken together, results from experiments 1 and 2 support the notion that anxiety and IU continue to play a role in the maintenance of PDA behaviours in adulthood, while participant descriptions implicate the role of anticipatory responses to uncertainty in the maintenance of demand avoidant behaviours in adults.
The environmental citizenship opinions questionnaire: a self-assessment tool for secondary students
Authors: van Harskamp Michiel , Knippels Marie-Christine P. J. , Boeve-de Pauw Jelle N. A. , van Joolingen Wouter R.
Published: July 2023

Introduction

We present a validated instrument for assessing Environmental Citizenship (EC) of students in lower secondary education. The Environmental Citizenship Opinions (ECO) questionnaire focusses on general citizenship components, key sustainability competences, and Socio-Scientific Reasoning aspects. By combining these domains, our work provides a needed innovation as these different aspects of EC have not previously been covered in one single, balanced and validated measurement instrument.

Methods

The ECO questionnaire was validated through a pilot round and a subsequent large-scale study (781 lower secondary students). Several rounds of Confirmatory Factor Analysis resulted in a final model of 38 items divided in 7 first order and 5 s order constructs.

Results

The final model fit statistics indicate near excellent quality of our model (RMSEA = 0.036, CFI = 0.93, TLI = 0.93, SRMR = 0.05), which consists of EC knowledge, EC attitudes, EC skills, EC reflection and complexity of EC issues. Calculations on the relative attribution of each of the five main constructs to overall environmental sustainability citizenship, highlight that attitudes and reflection skills are the most important constituents.

Discussion

Our result present the ECO questionnaire as a valuable, valid and reliable tool to measure environmental citizenship of students. Applications in practice include monitoring student’s development and supporting teachers during the challenging task of effective teaching for EC in and outside the classroom.
Towards visceral fat estimation at population scale: correlation of visceral adipose tissue assessment using three-dimensional cross-sectional imaging with BIA, DXA, and single-slice CT
Authors: Chan Benjamin , Yu Yan , Huang Fan , Vardhanabhuti Varut
Published: July 2023

Background

In terms of assessing obesity-associated risk, quantification of visceral adipose tissue (VAT) has become increasingly important in risk assessment for cardiovascular and metabolic diseases. However, differences exist in the accuracy of various modalities, with a lack of up-to-date comparison with three-dimensional whole volume assessment.

Aims

Using CT or MRI three-dimensional whole volume VAT as a reference, we evaluated the correlation of various commonly used modalities and techniques namely body impedance analysis (BIA), dual-energy x-ray absorptiometry (DXA) as well as single slice CT to establish how these methods compare.

Methods

We designed the study in two parts. First, we performed an intra-individual comparison of the 4558 participants from the UK Biobank cohorts with matching data of MRI abdominal body composition, DXA with VAT estimation, and BIA. Second, we evaluated 174 CT scans from the publicly available dataset to assess the correlation of the commonly used single-slice technique compared to three-dimensional VAT volume.

Results

Across the UK Biobank cohort, the DXA-derived VAT measurement correlated better (R2 0.94, p<0.0001) than BIA (R2 0.49, p<0.0001) with reference three-dimensional volume on MRI. However, DXA-derived VAT correlation was worse for participants with a BMI of < 20 (R2 = 0.62, p=0.0013). A commonly used single slice method on CT demonstrated a modest correlation (R2 between 0.51 – 0.64), with best values at L3- and L4 (R2 L3 = 0.63, p<0.0001; L4 = 0.64, p<0.0001) compared to reference three-dimensional volume. Combining multiple slices yielded a better correlation, with a strong correlation when L2-L3 levels were combined (R2 = 0.92, p<0.0001).

Conclusion

When deployed at scale, DXA-derived VAT volume measurement shows excellent correlation with three-dimensional volume on MRI based on the UK Biobank cohort. Whereas a single slice CT technique demonstrated moderate correlation with three-dimensional volume on CT, with a stronger correlation achieved when multiple levels were combined.
Metabolism and senescence in the immune microenvironment of osteosarcoma: focus on new therapeutic strategies
Authors: Ying Hui , Li Zhi-Qiang , Li Meng-Pan , Liu Wen-Cai
Published: July 2023

Osteosarcoma is a highly aggressive and metastatic malignant tumor. It has the highest incidence of all malignant bone tumors and is one of the most common solid tumors in children and adolescents. Osteosarcoma tissues are often richly infiltrated with inflammatory cells, including tumor-associated macrophages, lymphocytes, and dendritic cells, forming a complex immune microenvironment. The expression of immune checkpoint molecules is also high in osteosarcoma tissues, which may be involved in the mechanism of anti-tumor immune escape. Metabolism and senescence are closely related to the immune microenvironment, and disturbances in metabolism and senescence may have important effects on the immune microenvironment, thereby affecting immune cell function and immune responses. Metabolic modulation and anti-senescence therapy are gaining the attention of researchers as emerging immunotherapeutic strategies for tumors. Through an in-depth study of the interconnection of metabolism and anti- senescence in the tumor immune microenvironment and its regulatory mechanism on immune cell function and immune response, more precise therapeutic strategies can be developed. Combined with the screening and application of biomarkers, personalized treatment can be achieved to improve therapeutic efficacy and provide a scientific basis for clinical decision-making. Metabolic modulation and anti- senescence therapy can also be combined with other immunotherapy approaches, such as immune checkpoint inhibitors and tumor vaccines, to form a multi-level and multi-dimensional immunotherapy strategy, thus further enhancing the effect of immunotherapy. Multidisciplinary cooperation and integrated treatment can optimize the treatment plan and maximize the survival rate and quality of life of patients. Future research and clinical practice will further advance this field, promising more effective treatment options for patients with osteosarcoma. In this review, we reviewed metabolic and senescence characteristics in the immune microenvironment of osteosarcoma and related immunotherapies, and provide a reference for development of more personalized and effective therapeutic strategies.
Antibody-based soluble and membrane-bound TWEAK mimicking agonists with FcγR-independent activity
Authors: Zaitseva Olena , Hoffmann Annett , Löst Margaretha , Anany Mohamed A. , Zhang Tengyu , Kucka Kirstin , Wiegering Armin , Otto Christoph , Wajant Harald
Published: July 2023

Fibroblast growth factor (FGF)-inducible 14 (Fn14) activates the classical and alternative NFκB (nuclear factor ‘kappa-light-chain-enhancer’ of activated B-cells) signaling pathway but also enhances tumor necrosis factor (TNF)-induced cell death. Fn14 expression is upregulated in non-hematopoietic cells during tissue injury and is also often highly expressed in solid cancers. In view of the latter, there were and are considerable preclinical efforts to target Fn14 for tumor therapy, either by exploiting Fn14 as a target for antibodies with cytotoxic activity (e.g. antibody-dependent cellular cytotoxicity (ADCC)-inducing IgG variants, antibody drug conjugates) or by blocking antibodies with the aim to interfere with protumoral Fn14 activities. Noteworthy, there are yet no attempts to target Fn14 with agonistic Fc effector function silenced antibodies to unleash the proinflammatory and cell death-enhancing activities of this receptor for tumor therapy. This is certainly not at least due to the fact that anti-Fn14 antibodies only act as effective agonists when they are presented bound to Fcγ receptors (FcγR). Thus, there are so far no antibodies that robustly and selectively engage Fn14 signaling without triggering unwanted FcγR-mediated activities. In this study, we investigated a panel of variants of the anti-Fn14 antibody 18D1 of different valencies and domain architectures with respect to their inherent FcγR-independent ability to trigger Fn14-associated signaling pathways. In contrast to conventional 18D1, the majority of 18D1 antibody variants with four or more Fn14 binding sites displayed a strong ability to trigger the alternative NFκB pathway and to enhance TNF-induced cell death and therefore resemble in their activity soluble (TNF)-like weak inducer of apoptosis (TWEAK), one form of the natural occurring ligand of Fn14. Noteworthy, activation of the classical NFκB pathway, which naturally is predominately triggered by membrane-bound TWEAK but not soluble TWEAK, was preferentially observed with a subset of constructs containing Fn14 binding sites at opposing sites of the IgG scaffold, e.g. IgG1-scFv fusion proteins. A superior ability of IgG1-scFv fusion proteins to trigger classical NFκB signaling was also observed with the anti-Fn14 antibody PDL192 suggesting that we identified generic structures for Fn14 antibody variants mimicking soluble and membrane-bound TWEAK.
The recombinase activating genes: architects of immune diversity during lymphocyte development
Authors: Braams Merijn , Pike-Overzet Karin , Staal Frank J. T.
Published: July 2023

The mature lymphocyte population of a healthy individual has the remarkable ability to recognise an immense variety of antigens. Instead of encoding a unique gene for each potential antigen receptor, evolution has used gene rearrangements, also known as variable, diversity, and joining gene segment (V(D)J) recombination. This process is critical for lymphocyte development and relies on recombination-activating genes-1 (RAG1) and RAG2, here collectively referred to as RAG. RAG serves as powerful genome editing tools for lymphocytes and is strictly regulated to prevent dysregulation. However, in the case of dysregulation, RAG has been implicated in cases of cancer, autoimmunity and severe combined immunodeficiency (SCID). This review examines functional protein domains and motifs of RAG, describes advances in our understanding of the function and (dys)regulation of RAG, discuss new therapeutic options, such as gene therapy, for RAG deficiencies, and explore in vitro and in vivo methods for determining RAG activity and target specificity.
A prognostic nomogram for the cancer-specific survival of white patients with invasive melanoma at BANS sites based on the Surveillance, Epidemiology, and End Results database
Authors: Huang Jia-nan , Yu Hai , Wan Yang , Ming Wai-Kit , Situ Fangmin , Zhu Leqing , Jiang Yuzhen , Wu U. Tim , Huang WenHsien Ethan , Chen Wenhui , Lyu Jun , Deng Liehua
Published: July 2023

Objective

The purpose of this study was to develop a comprehensive nomogram for the cancer-specific survival (CSS) of white patients with invasive melanoma at back, posterior arm, posterior neck, and posterior scalp (BANS) sites and to determine the validity of the nomogram by comparing it with the conventional American Joint Committee on Cancer (AJCC) staging system.

Methods

This study analyzed the patients with invasive melanoma in the Surveillance, Epidemiology, and End Results (SEER) database. R software was used to randomly divide the patients into training and validation cohorts at a ratio of 7:3. Multivariable Cox regression was used to identify predictive variables. The new survival nomogram was compared with the AJCC prognosis model using the concordance index (C-index), area under the receiver operating characteristic (ROC) curve (AUC), net reclassification index (NRI), integrated discrimination index (IDI), calibration plotting, and decision-curve analysis (DCA).

Results

A novel nomogram was established to determine the 3-, 5-, and 8-year CSS probabilities of patients with invasive melanoma. According to the nomogram, the Age at Diagnosis had the greatest influence on CSS in invasive melanoma, followed by Bone Metastasis, AJCC, Stage, Liver Metastasis, Histologic Subtype, Brain Metastasis, Ulceration, and Primary Site. The nomogram had a higher C-index than the AJCC staging system in both the training (0.850 versus 0.799) and validation (0.829 versus 0.783) cohorts. Calibration plotting demonstrated that the model had good calibration ability. The nomogram outperformed the AJCC staging system in terms of AUC, NRI, IDI, and DCA.

Conclusion

This was the first study to develop and evaluate a comprehensive nomogram for the CSS of white patients with invasive melanoma at BANS sites using the SEER database. The novel nomogram can assist clinical staff in predicting the 3-, 5-, and 8-year CSS probabilities of patients with invasive melanoma more accurately than can the AJCC staging system.
Risk factors for hypoxaemia following hip fracture surgery in elderly patients who recovered from COVID-19: a multicentre retrospective study
Authors: Chi Wen , Pang Peng , Luo Zhenguo , Liu Xiaobing , Cai Wenbo , Li Wangyang , Hao Jianhong
Published: July 2023

Objectives

To explore the risk factors associated with postoperative hypoxaemia in elderly patients who have recovered from coronavirus disease (COVID-19) and underwent hip fracture surgery in the short term.

Design

Multicentre retrospective study.

Setting

The study was performed in three first 3A-grade hospitals in China.

Participants

A sequential sampling method was applied to select study participants. Medical records of 392 patients aged ≥65 years who had recovered from COVID-19 and underwent hip fracture surgery at three hospitals in China between 1 November, 2022, and 15 February, 2023, were reviewed.

Interventions

Patients were assigned to hypoxaemia or non-hypoxaemia groups, according to whether hypoxaemia occurred after surgery. Univariate and multivariate logistic regression analyses were used to identify independent risk factors for postoperative hypoxaemia.

Results

The incidence of postoperative hypoxaemia was 38.01%. Statistically significant differences were found between the two groups in terms of age, body mass index (BMI), American Society of Anesthesiologists (ASA) classification, presence of expectoration symptoms, preoperative hypoxaemia, chronic obstructive pulmonary disease, pulmonary inflammation, time between recovery from COVID-19 and surgery, anaesthetic mode, surgical procedure, intraoperative blood loss, intraoperative infusion, duration of surgery, and length of hospital stay (p < 0.05). Furthermore, patients with BMI ≥28.0 kg/m2, expectoration symptoms, presence of preoperative hypoxaemia, ASA classification III, time between recovery from COVID-19 and surgery ≤2 weeks, and general anaesthesia were potential risk factors for postoperative hypoxaemia.

Conclusion

Obesity, expectoration symptoms, preoperative hypoxaemia, ASA classification III, time between recovery from COVID-19 and surgery ≤2 weeks, and general anaesthesia were potential risk factors for postoperative hypoxaemia in elderly patients who recovered from COVID-19 and underwent hip fracture surgery in the short term.
Endophytic fungi: hidden treasure chest of antimicrobial metabolites interrelationship of endophytes and metabolites
Authors: Jha Priyanka , Kaur Tamanna , Chhabra Ishita , Panja Avirup , Paul Sushreeta , Kumar Vijay , Malik Tabarak
Published: July 2023

Endophytic fungi comprise host-associated fungal communities which thrive within the tissues of host plants and produce a diverse range of secondary metabolites with various bioactive attributes. The metabolites such as phenols, polyketides, saponins, alkaloids help to mitigate biotic and abiotic stresses, fight against pathogen attacks and enhance the plant immune system. We present an overview of the association of endophytic fungal communities with a plant host and discuss molecular mechanisms induced during their symbiotic interaction. The overview focuses on the secondary metabolites (especially those of terpenoid nature) secreted by endophytic fungi and their respective function. The recent advancement in multi-omics approaches paved the way for identification of these metabolites and their characterization via comparative analysis of extensive omics datasets. This study also elaborates on the role of diverse endophytic fungi associated with key agricultural crops and hence important for sustainability of agriculture.
A systematic review of the barcoding strategy that contributes to COVID-19 diagnostics at a population level
Authors: Chen Heng-Chang
Published: July 2023

The outbreak of SARS-CoV-2 has made us more alert to the importance of viral diagnostics at a population level to rapidly control the spread of the disease. The critical question would be how to scale up testing capacity and perform a diagnostic test in a high-throughput manner with robust results and affordable costs. Here, the latest 26 articles using barcoding technology for COVID-19 diagnostics and biologically-relevant studies are reviewed. Barcodes are molecular tags, that allow proceeding an array of samples at once. To date, barcoding technology followed by high-throughput sequencing has been made for molecular diagnostics for SARS-CoV-2 infections because it can synchronously analyze up to tens of thousands of clinical samples within a short diagnostic time. Essentially, this technology can also be used together with different biotechnologies, allowing for investigation with resolution of single molecules. In this Mini-Review, I first explain the general principle of the barcoding strategy and then put forward recent studies using this technology to accomplish COVID-19 diagnostics and basic research. In the meantime, I provide the viewpoint to improve the current COVID-19 diagnostic strategy with potential solutions. Finally, and importantly, two practical ideas about how barcodes can be further applied in studying SARS-CoV-2 to accelerate our understanding of this virus are proposed.
Neonatal Zika virus infection causes transient perineuronal net degradation
Authors: Engel Kaliroi , Lee Ha-Na , Tewari Bhanu P. , Lewkowicz Aaron P. , Ireland Derek D. C. , Manangeeswaran Mohanraj , Verthelyi Daniela
Published: July 2023

Perineuronal nets (PNNs) form a specialized extracellular matrix that predominantly surrounds parvalbumin (PV)-expressing GABAergic inhibitory interneurons and help regulate neuronal activity. Their formation early in the postnatal period is regulated by neuronal signaling and glial activation raising concerns that part of the long-term effects ascribed to perinatal viral infections could be mediated by altered PNN formation. Previously, we developed a model of neonatal Zika virus (ZIKV) infection where mice have lifelong neurological sequelae that includes motor disfunction and reduced anxiety coupled with a persistent low-grade expression in proinflammatory markers despite resolving the acute infection. Here, we demonstrate that ZIKV infection to P1 neonatal mice results in a reduction of PNN formation during the acute disease with significant reduction in Wisteria floribunda agglutinin (WFA) staining at the peak of infection [15 days post infection (dpi)] that persisted after the symptoms resolved (30 dpi). At 60 dpi, when there is residual inflammation in the CNS, the number of WFA+ cells and the level of WFA staining as well as levels of aggrecan and brevican in the brains of convalescent mice were not different from those in uninfected controls, however, there was increased frequency of PNNs with an immature phenotype. Over time the impact of the perinatal infection became less evident and there were no clear differences in PNN morphology between the groups at 1 year post infection. Of note, the reduction in PNNs during acute ZIKV infection was not associated with decreased mRNA levels of aggrecan or brevican, but increased levels of degraded aggrecan and brevican indicating increased PNN degradation. These changes were associated with increased expression of matrix metalloproteinase 12 (MMP12) and MMP19, but not MMP9, a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS4) or ADAMTS5. Together our findings indicate that infection at the time of PNN development interferes with PNN formation, but the nets can reform once the infection and inflammation subside.
Safety and efficacy of rapid withdrawal of anti-seizure medication during long-term video-EEG monitoring
Authors: Liu Jiao , Chen Deng , Xu Yingchun , Zhang Yu , Liu Ling
Published: July 2023

Objective

Anti-seizure medications (ASMs) are often withdrawn during long-term video-EEG monitoring (LTM) to allow pre-surgical evaluation. Herein, we evaluated the safety and efficacy of ultra-rapid withdrawal (URW) and rapid withdrawal (RW) of ASMs in an epilepsy monitoring unit (EMU).

Methods

This retrospective study examined all consecutive patients admitted to our EMU between May 2021 and October 2022. Patients were classified into the URW and RW groups according to the way ASMs were withdrawn. We compared the efficacy and safety of the procedures used in the groups in terms of duration of LTM, latency to the first seizure, and incidence of focal to bilateral tonic–clonic seizures (FBTCS), seizure clusters (SC), and status epilepticus (SE).

Results

Overall, 110 patients (38 women) were included. The mean age of patients at the time of LTM was 29 years. All medications were stopped on admission for monitoring in the URW group (n = 75), while in the RW group (n = 35) ASMs were withdrawn within 1 day. In both groups, the duration of LTM was approximately 3 days: URW group (2.9 ± 0.5 days) and RW group (3.1 ± 0.8 days). The latency to the first seizure was significantly different between the two groups; however, there were no differences between the two groups in terms of the distribution of FBTCS, SC, or SE, number of seizures, and the requirement for intravenous rescue medication was low.

Conclusion

The rapid withdrawal of ASMs to provoke seizures during monitoring for pre-surgical evaluation following the URW protocol was as effective and safe as with RW. Ultra-rapid ASM withdrawal has the benefits of reducing LTM duration and shortening the time to first seizure compared to rapid medication tapering.
A task force for diagnosis and treatment of people with Alzheimer’s disease in Latin America
Authors: Lopera Francisco , Custodio Nilton , Rico-Restrepo Mariana , Allegri Ricardo F. , Barrientos José Domingo , Garcia Batres Estuardo , Calandri Ismael L. , Calero Moscoso Cristian , Caramelli Paulo , Duran Quiroz Juan Carlos , Jansen Angela Marie , Mimenza Alvarado Alberto José , Nitrini Ricardo , Parodi Jose F. , Ramos Claudia , Slachevsky Andrea , Brucki Sonia María Dozzi
Published: July 2023

Alzheimer’s disease (AD) represents a substantial burden to patients, their caregivers, health systems, and society in Latin America and the Caribbean (LAC). This impact is exacerbated by limited access to diagnosis, specialized care, and therapies for AD within and among nations. The region has varied geographic, ethnic, cultural, and economic conditions, which create unique challenges to AD diagnosis and management. To address these issues, the Americas Health Foundation convened a panel of eight neurologists, geriatricians, and psychiatrists from Argentina, Brazil, Colombia, Ecuador, Guatemala, Mexico, and Peru who are experts in AD for a three-day virtual meeting to discuss best practices for AD diagnosis and treatment in LAC and create a manuscript offering recommendations to address identified barriers. In LAC, several barriers hamper diagnosing and treating people with dementia. These barriers include access to healthcare, fragmented healthcare systems, limited research funding, unstandardized diagnosis and treatment, genetic heterogeneity, and varying social determinants of health. Additional training for physicians and other healthcare workers at the primary care level, region-specific or adequately adapted cognitive tests, increased public healthcare insurance coverage of testing and treatment, and dedicated search strategies to detect populations with gene variants associated with AD are among the recommendations to improve the landscape of AD.
Boost your brain: a simple 100% normobaric oxygen treatment improves human motor learning processes
Authors: Wang Zheng , Spielmann Guillaume , Johannsen Neil , Greenway Frank , Irving Brian A. , Dalecki Marc
Published: July 2023

Introduction

Human motor learning processes are a fundamental part of our daily lives and can be adversely affected by neurologic conditions. Motor learning largely depends on successfully integrating cognitive and motor-related sensory information, and a simple, easily accessible treatment that could enhance such processes would be exciting and clinically impactful. Normobaric 100% oxygen treatment (NbOxTr) is often used as a first-line intervention to improve survival rates of brain cells in neurological trauma, and recent work indicates that improvements in elements crucial for cognitive-motor-related functions can occur during NbOxTr. However, whether NbOxTr can enhance the motor learning processes of healthy human brains is unknown. Here, we investigated whether a brief NbOxTr administered via nasal cannula improves motor learning processes during a visuomotor adaptation task where participants adapt to a visual distortion between visual feedback and hand movements.

Methods

40 healthy young adults (M = 21 years) were randomly assigned to a NbOxTr (N = 20; 100% oxygen) or air (N = 20; regular air) group and went through four typical visuomotor adaptation phases (Baseline, Adaptation, After-Effect, Refresher). Gas treatment (flow rate 5 L/min) was only administered during the Adaptation phase of the visuomotor experiment, in both groups.

Results

The NbOxTr provided during the Adaptation phase led to significantly faster and about 30% improved learning (p < 0.05). Notably, these motor learning improvements consolidated into the subsequent experiment phases, i.e., after the gas treatment was terminated (p < 0.05).

Discussion

We conclude that this simple and brief NbOxTr dramatically improved fundamental human motor learning processes and may provide promising potential for neurorehabilitation and skill-learning approaches. Further studies should investigate whether similar improvements exist in elderly and neurologically impaired individuals, other motor learning tasks, and also long-lasting effects.
Evaluation of Bioactive Compounds and Bioactivities in Plum (Prunus salicina Lindl.) Wine
Authors: Liu Guoming , Wei Ping , Tang Yayuan , Pang Yiyang , Sun Jian , Li Jiemin , Rao Chuanyan , Wu Cuiqiong , He Xuemei , Li Li , Ling Dongning , Chen Xi
Published: July 2023

With the increase in demand of fruit wine year by year, it is necessary to develop novel fruit wine with high functional activities. Prunus salicina Lindl. (named as Niuxin plum) is a remarkable material for brewing fruit wine owing to its suitable sugar-acid ratio, characteristic aroma and bioactive compounds. This study intends to modify the fermentation technology, identify and quantify nutritional compositions and volatile profiles, as well as bioactive substances in Niuxin plum wine, as well as evaluate the antioxidant and hypoglycemic activities in vitro of major bioactive components from Niuxin plum wine. According to single-factor and orthogonal tests, the optimal fermentation conditions of 13.1% vol Niuxin plum wine should be Saccharomyces cerevisiae Lalvin EC1118 at 0.1% and a fermentation temperature of 20°C for 7 days. A total of 17 amino acids, 9 mineral elements, 4 vitamins, and 55 aromatic components were detected in plum wine. Polysaccharides from Niuxin plum wine (named as NPWPs) served as the major bioactive components. The NPWP with a molecular weight over 1,000 kDa (NPWP-10) demonstrated extraordinary DPPH free radical scavenging capacity and α-glucosidase inhibitory activity among all NPWPs having different molecular weight. Moreover, the structural characterization of NPWP-10 was also analyzed by high performance liquid chromatography (HPLC), fourier-transform infrared (FT-IR) and nuclear magnetic resonance (NMR) spectra studies. NPWP-10 was composed of mannose, rhamnose, arabinose, galactose and galacturonic acid with molar ratios of 2.570:1.775:1.045:1.037:1. NPWP-10 contained α-configuration as the main component and β-configuration as the auxiliary component. This study highlights NPWP-10 is an importantly biological polysaccharide from Niuxin plum wine, as well as provides a scientific basis for developing the plum wine industry.
Rhabdoid meningioma with a history of Budd-Chiari syndrome: a case report and review of the literature
Authors: Zeng Ying , Zhang Jing , Jian Wei , Zhang Yong , Yang Ying , Li Rongqing , Fu Qiaofen
Published: July 2023

Background

Rhabdoid meningioma and Budd-Chiari syndrome are both extremely rare, and there is no report describing the two diseases occurring in the same patient thus far. Herein, we showed an unusual case of rhabdoid meningioma with a history of Budd-Chiari syndrome.

Case presentation

The man was found to have abnormal liver function during physical examination in 2016 at 36 and was not paid attention to it. In 2019, he went to Beijing YouAn Hospital Affiliated to Capital Medical University for the decompensation of cirrhosis and was diagnosed with Budd-Chiari syndrome, subsequent angiography of the inferior vena cava combined with balloon dilatation were performed, the anticoagulation and hepatoprotective therapy were performed for a long time. When he turned 40 who had magnetic resonance imaging (MRI) that showed a left frontotemporal lobe space-occupying lesion, and postoperative pathological examination confirmed rhabdoid meningioma. He underwent surgery and postoperative adjuvant radiotherapy, but then he developed severe psychiatric symptoms and eventually succumbed to a lung infection two months after treatment.

Conclusions

Budd-Chiari syndrome and Rhabdoid meningiomas are both extremely rare diseases. To the best of our knowledge, there is no report that the two rare diseases occurred in the same patient, and this is the first case. However, whether there is any link between the two diseases is unclear, more researches are needed to confirm it in the future.
Racial and ethnic disparities in obesity and contributions of social determinants of health among boys with autism spectrum disorder
Authors: Magaña Sandy , Eliasziw Misha , Bowling April , Must Aviva
Published: July 2023

Children with autism spectrum disorders (ASD) are at greater obesity risk compared to typically developing peers. Although many potential risk factors for this relationship have been identified, the causal chain must be better understood, particularly modifiable social determinants of obesity risk in ASD, and especially for children with ASD from minoritized racial/ethnic groups. We aimed to: (1) examine racial/ethnic disparities in obesity status in boys with ASD; (2) assess associations between social determinants of health and obesity status; and (3) understand if social determinants of health factors mediate the relationship between race/ethnicity and obesity status for these youth. We used data for 124 boys, aged 9–10 with ASD enrolled in an ongoing longitudinal study. Social determinants of health explored included socioeconomic position, Area Deprivation Index, neighborhood safety, food and housing insecurity, and racial/ethnic discrimination. The racial/ethnic distribution was: 17.1% Black, 14.6% Latino, and 68.3% White; average age was 10 years. Both Black (PR 2.57, 95% CI: 1.26–5.26) and Latino boys (PR 2.08, 95% CI: 1.08–4.03) with ASD were more likely to be obese than their White peers. While there were significant differences in some social determinants of health by race/ethnicity, only food insecurity mediated associations between race/ethnicity (Black vs. White) and obesity. The striking disparities in obesity and differences in social determinants of health between Black and Latino children with ASD compared to White children emphasize the need to identify factors that contribute to healthy weight among these children and to address these factors in practice.
Impact of the omicron phase on a highly advanced medical facility in Japan
Authors: Yamagishi Hirokazu , Tamura Daisuke , Aoyagi Jun , Suzuki Shun , Mizobe Yoshitaka , Wakae Keizo , Yamagata Takanori , Tajima Toshihiro , Osaka Hitoshi
Published: July 2023

Background

Eight waves of the coronavirus disease 2019 (COVID-19) epidemic have been observed in Japan. This retrospective study was conducted to clarify the clinical characteristics of pediatric COVID-19 patients.

Methods

We studied 121 patients admitted to the Jichi Children's Medical Center Tochigi between April 2020 and March 2023. Incidence of pediatric COVID-19 in Tochigi Prefecture was used to examine hospitalization and severe illness rates.

Results

The mean age of the patients was 3 years and 8 months. One hundred and eleven patients (91.7%) were hospitalized after January 2022 (after the 6th wave), when the Omicron strain became endemic in Japan. Convulsions occurred in 30 patients (24.8%), all of whom were admitted after the 6th wave. Twenty-three of the 30 patients had no underlying disease. Eleven patients (9.1%) were diagnosed with acute encephalopathy. One patient died due to hemorrhagic shock and encephalopathy syndrome and two had sequelae after the 6th wave. The patient who died due to encephalopathy had hypercytokinemia. In the Tochigi Prefecture, the number of pediatric COVID-19 patients increased after the 6th wave, but the hospitalization rate declined. The rate of severe illness did not change before the end of 5th and after the 6th wave.

Conclusion

Although the rate of severe illness in patients with pediatric COVID-19 did not increase after the 6th wave, some patients had complicated critical illnesses. Systemic inflammatory reaction was considered to have been associated with the severe encephalopathy.
Preparation of a Sunitinib loaded microemulsion for ocular delivery and evaluation for the treatment of corneal neovascularization in vitro and in vivo
Authors: Shi Jieran , Yang Jingjing , Xu Haohang , Luo Qing , Sun Jun , Zhang Yali , Liang Zhen , Zhao Ningmin , Zhang Junjie
Published: July 2023

Background: Corneal neovascularization (CNV) is a pathological condition that can disrupt corneal transparency, thus harming visual acuity. However, there is no effective drug to treat CNV. Sunitinib (STB), a small-molecule multiple receptor tyrosine kinase inhibitor, was shown to have an effect on CNV. The purpose of this study was to develop an STB microemulsion (STB-ME) eye drop to inhibit CNV by topical application.

Methods: We successfully prepared an STB-ME by the phase inversion emulsification method, and the physicochemical properties of STB-MEs were investigated. The short-term storage stability, cytotoxicity to human corneal epithelial cells, drug release, ocular irritation, ocular pharmacokinetics and the inhibitory effect on CNV were evaluated in vitro and in vivo.

Results: The optimal formulation of STB-ME is composed of oleic acid, CRH 40, Transcutol P, water and sodium hyaluronate (SH). It is a uniform spherical particle with a mean droplet size of 18.74 ± 0.09 nm and a polydispersity index of 0.196 ± 0.004. In the in vitro drug release results, STB-ME showed sustained release and was best fitted by a Korsmeyer-Peppas model (R2 = 0.9960). The results of the ocular pharmacokinetics in rabbits showed that the formulation containing SH increased the bioavailability in the cornea (2.47-fold) and conjunctiva (2.14-fold). STB-ME (0.05% and 0.1%), administered topically, suppressed alkali burn-induced CNV in mice more effectively than saline, and high-dose (0.1%) STB-ME had similar efficacy to dexamethasone (0.025%).

Conclusion: This study provides a promising formulation of STB-ME for the inhibition of CNV by topical administration, which has the excellent characteristics of effectiveness, sustained release and high ocular bioavailability.
Polysaccharides from natural resource: ameliorate type 2 diabetes mellitus via regulation of oxidative stress network
Authors: He Li-Ying , Li Yong , Niu Shu-Qi , Bai Jing , Liu Si-Jing , Guo Jin-Lin
Published: July 2023

Diabetes mellitus (DM) is a group of metabolic diseases characterized by hyperglycemia that can occur in children, adults, elderly people, and pregnant women. Oxidative stress is a significant adverse factor in the pathogenesis of DM, especially type 2 diabetes mellitus (T2DM), and metabolic syndrome. Natural polysaccharides are macromolecular compounds widely distributed in nature. Some polysaccharides derived from edible plants and microorganisms were reported as early as 10 years ago. However, the structural characterization of polysaccharides and their therapeutic mechanisms in diabetes are relatively shallow, limiting the application of polysaccharides. With further research, more natural polysaccharides have been reported to have antioxidant activity and therapeutic effects in diabetes, including plant polysaccharides, microbial polysaccharides, and polysaccharides from marine organisms and animals. Therefore, this paper summarizes the natural polysaccharides that have therapeutic potential for diabetes in the past 5 years, elucidating their pharmacological mechanisms and identified primary structures. It is expected to provide some reference for the application of polysaccharides, and provide a valuable resource for the development of new diabetic drugs.