bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of ossification of the posterior longitudinal ligament (OPLL) in the Pacific populations in Auckland, New Zealand: A retrospective multicentre study
Authors: Tsai Yun‐Jung Jack , Doyle Anthony
Published: June 2024

Introduction

Primary objective was to investigate the prevalence of ossification of the posterior longitudinal ligament (OPLL) in a mixed demographic region, especially in the Pacific Island population. Secondary objective was to investigate the prevalence of diabetes mellitus and cervical diffuse skeletal hyperostosis (DISH) in patients with and without OPLL.

Methods

Using the local picture archiving and communication system (PACS), cervical spine computed tomography (CT) examinations over a 2‐month period were retrospectively assessed for the presence of OPLL. Basic demographic data were recorded—gender, age, ethnicity, presence of cervical DISH and the presence or absence of diabetes mellitus.

Results

A total of 1692 CT examinations were included in the study. The distribution of the ethnic groups was 57.3% European, 12.09% Pacific peoples, 11.9% Māori, 11.53% Asian, 0.95% Middle Eastern/Latin American/African and 6.3% not specified. Overall, 47 cases of OPPL were identified (2.78%). The prevalence of OPPL in the Pacific ethnic groups was significantly higher than the European ethnic group 8.4% versus 0.6%, P < 0.05. The prevalence of OPLL was also significantly higher in the Asian (6.9%) and Māori (3.6%) than in the European ethnic group, P < 0.05. A significantly higher proportion of the patients with OPLL had underlying diabetes 20/47 (42.6%) compared with the study population 196/1692 (11.6%), P < 0.05. Seven cases of OPPL (14.9%) had associated cervical DISH, which was significantly higher compared with the study group (23/1692), P < 0.05. Using the Japanese Ministry of Health and Welfare classification system4, segmental type was the most common (34/47, 72.3%), followed by mixed (14.9%) and continuous types (12.8%).

Conclusion

The prevalence of OPLL is significantly higher among the Pacific populations in Auckland. There is also increased prevalence in the Asian and Māori populations.
Lipocalin‐2 as a prognostic biomarker and its association with systemic inflammation in small cell lung cancer
Authors: Go Se‐Il , Yang Jung Wook , Lee Woo Je , Jeong Eun Jeong , Park Sungwoo , Lee Gyeong‐Won
Published: June 2024

Background

Systemic inflammation is believed to contribute to small cell lung cancer (SCLC) progression, but the underlying relationship remains unclear. Lipocalin‐2, a potential biomarker of inflammation, has been implicated in various cancers but its prognostic value in SCLC is underexplored.

Methods

We retrospectively analyzed 191 patients with SCLC (72 with limited‐stage [LD] and 119 with extensive‐stage) treated using platinum‐based chemotherapy. Lipocalin‐2 expression was evaluated using immunohistochemistry. Optimal cutoff values for lipocalin‐2 and neutrophil‐to‐lymphocyte ratio (NLR) were determined using time‐dependent receiver operating characteristic curve analysis. The pectoralis muscle index was used to assess sarcopenia.

Results

In LD‐SCLC, high lipocalin‐2 expression was associated with worse progression‐free survival (PFS; median: 7.0 vs. 15.9 months, p = 0.015) and overall survival (OS; median: 12.9 vs. 30.3 months, p = 0.035) compared with low lipocalin‐2 expression. Patients were stratified into three prognostic groups by combining lipocalin‐2 with NLR: low lipocalin‐2/low NLR, high lipocalin‐2/low NLR or low lipocalin‐2/high NLR, and high lipocalin‐2/high NLR (median PFS: 17.3 vs. 11.0 vs. 6.3 months, p = 0.004; median OS: 30.5 vs. 17.3 vs. 8.6 months, p = 0.002). Similar trends were observed when combining lipocalin‐2 with the pectoralis muscle index. High lipocalin‐2 expression was also associated with lower complete response rates (18.9% vs. 34.3%, p = 0.035). No significant prognostic implications were found for lipocalin‐2 in extensive‐stage SCLC.

Conclusions

High lipocalin‐2 expression is potentially associated with poorer survival in LD‐SCLC. Combining lipocalin‐2 with other inflammation‐related markers could improve prognostic stratification.
Deficiency of SECTM1 impairs corneal wound healing in aging
Authors: Zhu Jin , Lan Xihong , Mo Kunlun , Zhang Wang , Huang Ying , Tan Jieying , Wang Li , Ji Jianping , Ke Qiong , Ouyang Hong
Published: June 2024

The corneal epithelium is the outermost transparent barrier of the eyeball and undergoes continuous self‐renewal by limbal stem cells (LSCs) during its lifetime; however, the impact of aging on LSCs remains largely unknown. Here, we showed that the healing ability of the cornea in elderly macaques (Macaca fascicularis) was significantly decreased compared to that of younger macaques. This delayed wound closure accompanied a disordered cell arrangement and corneal opacity. A novel cytokine, Secreted and Transmembrane 1 (SECTM1), was found to facilitate corneal healing and was upregulated in young macaques upon wounding. Mechanistically, SECTM1 is essential for LSC migration and proliferation, and may partially function through Cell Division Cycle Associated 7 (CDCA7). Notably, the topical application of SECTM1 to aged wounded corneas dramatically promoted re‐epithelialization and improved corneal transparency in both mice and macaques. Our work suggests that aging may impair the expression of healing response factors and injury repair in non‐human primate corneas, and that SECTM1 application could potentially benefit corneal wound healing in clinical treatment.
Barriers to the introduction of novel advanced targeted treatments for Australian dermatology patients: Are skin diseases symptomatic of a systemic healthcare problem?
Authors: Mahar Patrick David , Crothers Anna , Foley Peter , Thomas Joseph
Published: June 2024

The aim of this article is to provide education to clinicians about certain barriers restricting the use of advanced targeted treatments in Australian health care. For illustrative purposes, the article focuses on dermatological conditions, but the content is relevant to all specialties that treat inflammatory and chronic diseases. Barriers to care discussed result in a lower than necessary standard of care for patients in Australia despite important advancements in medicine.
Culturally responsive occupational therapy practice with First Nations Peoples—A scoping review
Authors: Meechan Elizabeth , Geia Lynore , Taylor Marayah , Murray Donna , Stothers Kylie , Gibson Paul , Devine Sue , Barker Ruth
Published: June 2024

Introduction

First Nations Peoples consistently demonstrate strength and resilience in navigating systemic health care inequities. Acknowledging racism as a health determinant underscores the urgent need for a counterforce—cultural safety. Indigenous Allied Health Australia (IAHA) contends that with cultural responsiveness, the health workforce can take action to create a culturally safe environment.

Objective

To explore features of culturally responsive occupational therapy (OT) practice when providing a service with First Nations People and examine alignment of those features with the IAHA Cultural Responsiveness in Action Framework.

Design

A systematic scoping review was undertaken using CINAHL, Emcare, MEDLINE, PsychInfo and Scopus databases. Examples of culturally responsive OT practice with First Nations Peoples were mapped to the six IAHA Framework capabilities and confirmed by First Nations co‐authors.

Findings

OT practice with First Nations Peoples aligned with the six capabilities to varying degrees. The importance of OTs establishing relationships with First Nations People, applying self‐reflection to uncover cultural biases, and addressing limitations of the profession's Western foundations was evident.

Discussion

Recognising the interrelatedness of the six capabilities, the absence of some may result in a culturally unsafe experience for First Nations People. OTs must acknowledge the leadership of First Nations Peoples by privileging their voices and consider how established practices may reinforce oppressive systems.

Conclusion

To ensure a culturally safe environment for First Nations People, the OT profession must respect the leadership of First Nations Peoples and address the limitations of the profession's Western foundations to uphold the profession's core value of client‐centred care.
Management and outcomes of splenic injuries secondary to blunt trauma in patients presenting to major trauma hospitals in Aotearoa New Zealand
Authors: McGuinness Matthew James , Joseph Nejo , Xu William , Paterson Luke , McLaughlin Scott , Riordan Elisabeth , Isles Siobhan , Harmston Christopher
Published: June 2024

Background

Non‐operative management of splenic injuries has significantly increased in the last decade with an increased emphasis on splenic preservation. This shift was assisted by increased availability of angioembolization, however, potential geographical variability in access exists in Aotearoa New Zealand (AoNZ). The aim of this study was to assess the management of splenic injury across AoNZ.

Method

Five‐year retrospective study of all patients admitted to AoNZ hospitals with blunt major trauma and a splenic injury. Patients were identified using the National Trauma Registry and cross‐referenced with the National Minimum Data Set to determine their management. The primary outcome was the non‐operative rate.

Results

Seven hundred seventy‐three patients were included. Four hundred sixty‐nine presented to a tertiary major trauma hospital and 304 to a secondary major trauma hospital. A difference was found in the rate of non‐operative management between tertiary and secondary hospitals (P = 0.019). The rate of non‐operative management was similar in mild (P = 0.814) and moderate (P = 0.825) injuries, however, significantly higher in severe injuries in tertiary hospitals (P = 0.009). No difference in mortality rate was found.

Conclusion

This study found a difference in the management of splenic injuries between tertiary and secondary major trauma hospitals; predominantly due to a higher rate of operative management in patients with severe injuries at secondary hospitals. Despite this, no difference in mortality rate was found between tertiary and secondary hospitals.
Nima's “Incomplete” Humans: Storying Adolescents’ Black Inhabitations in Accra
Authors: Okoye Victoria Ogoegbunam
Published: June 2024

In this article, I story adolescents as “incomplete” human beings whose inventive modes of storytelling and inhabiting community space shape a “black sense of place” in the Nima neighbourhood of Accra, Ghana. In collaborative arts‐based research with Spread‐Out Initiative NGO, Nima adolescents share stories and narrate experiences that witness everyday violences, dispossession, and neglect and also small, meaningful openings they create together in community space. From this collaborative research, I locate Nima as a black geography situated in an African metaphysical universe where human, nonhuman, and spiritual worlds and Ghana's interconnected histories of enslavements and colonialism shape place. I contend that following these adolescents’ storied experiences and inventive black inhabitations through the framework of incompleteness offers ways of knowing these adolescents not as deficient or less‐than‐human, but full of possibility. By tracing the everyday ways adolescents deploy magic to extend themselves and their spatial potentials in concert with other incomplete human, nonhuman, and spiritual beings, I argue they produce black life. This approach extends black geographic thought, by honouring Nima adolescents and their stories of ever‐incomplete human becoming and weaving together black indigenous, migratory, and diasporic ways of knowing in global black relation.
The Coloniality of Space: Landscape, Aesthetics, and the Middle Classes in Dar es Salaam
Authors: Mercer Claire
Published: June 2024

In Dar es Salaam, an aesthetic politics of landscape shaped by the coloniality of space is central to middle‐class boundary work that drives the city's middle classes to congregate in the city's northern suburbs. The colonial city was divided into three racially marked zones that became known as uzunguni, uhindini, and uswahilini (the place of the European, Indian, and African, respectively). The coloniality of space remains as the spatial residue of this colonial enframing. It endures in an aesthetic politics of landscape in which ideas about what, and who, makes good urban space in terms of architecture, topography, and planning, and who deserves to live where. The paper examines how middle‐class suburban residents’ mobilisation of the coloniality of space naturalises existing social and spatial hierarchies in the city.
Effects of physical activity planning interventions on reducing sedentary behavior in parent–child dyads: A randomized controlled trial
Authors: Szczuka Zofia , Kulis Ewa , Banik Anna , Boberska Monika , Siwa Maria , Zaleskiewicz Hanna , Krzywicka Paulina , Paduszynska Natalia , Knoll Nina , Radtke Theda , Schenkel Konstantin , Dunton Genevieve F. , Luszczynska Aleksandra
Published: June 2024

Effects of parent–child dyad interventions on behavior remain unclear. This randomized controlled trial investigated if, compared with a control condition, three types of physical activity (PA) planning interventions (individual “I‐for‐me,” dyadic “we‐for‐me,” and collaborative “we‐for‐us”) would reduce sedentary behavior (SB) time in parents and their children. The study involved 247 dyads comprising parents (aged 29–66) and their children (aged 9–15), randomized into one of the three types of PA planning‐intervention arms or the control condition. Mixed models were applied to analyze data from a preregistered trial (NCT02713438) with the outcome of accelerometer‐measured SB time, assessed at 1‐week and 36‐week follow‐ups. Although children's SB remained unaffected by the planning interventions, a small reduction of SB time was found among parents in the collaborative (p = .048) and individual (p = .042) planning conditions. The effects were observed at the 1‐week follow‐up only. While short‐term reductions in parents' SB were achieved, these were not sustained long‐term. PA planning interventions delivered to parent–child dyads did not substantially reduce children's SB, which may be due to young people's needs of increased independence from their parents.
A heterotopic reading of heritage: The Village of Our Lady in Ka Ho, Macau
Authors: Ye Xi
Published: June 2024

Postcolonial Macau is keen to celebrate its colonial legacy to preserve its cultural distinctiveness. This study explores the reordering of a Portuguese colonial site, the Village of Our Lady in Ka Ho, into an architectural heritage in the broader postcolonial context. Employing the Foucauldian concept of ‘other spaces’, specifically ‘utopia’ and ‘heterotopia’, the study argues for the heterotopic nature of heritage. It identifies the discourses and material representations of heritage, their construction and their mirroring of mainstream social ideals. Heritage as heterotopia is a conceptual entity that informs and is realised with material objects. The discourse takes heritage spaces as mediums for performances through symbolic loading on material objects to demonstrate the space's otherness. In addition, colonial nostalgia emerges as a dominant narrative in shaping urban identity. The primary proposition of this research is that heritage is made through othering, and the otherness of heritage is presented through performing. Heritage‐making transforms the site from a ‘heterotopia of deviation’ to a ‘heterotopia of performance’, which reveals the societal transition from early modernity that advocates for scientific knowledge to postmodernity that embraces neoliberalism, and then to the arriving era of post‐postmodernity based on performatism.
Robot‐assisted radical prostatectomy with the Hugo™ robot‐assisted surgery system: A single‐center initial experience in Japan
Authors: Takahara Kiyoshi , Motonaga Tomonari , Nakamura Wataru , Saruta Masanobu , Nukaya Takuhisa , Takenaka Masashi , Zennami Kenji , Ichino Manabu , Sasaki Hitomi , Shiroki Ryoichi
Published: June 2024

Background

Recently, various novel robotic systems have been put into clinical use. The aim of the present study was to assess the perioperative outcomes of robot‐assisted radical prostatectomy (RARP) using the Hugo™ RAS system, one of brand‐new robot‐assisted surgical platforms.

Methods

We performed RARP with the Hugo™ RAS system in 13 cases of localized prostate cancer (PCa) between August 2023 and February 2024 at our hospital. The perioperative outcomes of these 13 patients were assessed.

Results

The median operative and console times were 197 (interquartile range [IQR], 187–228) and 134 min (IQR, 125–157), respectively. The median docking time was 7 min (IQR, 6–10), and the median estimated blood loss was 150 mL (IQR, 80–250). The vesical catheter was removed on postoperative day 6 in all cases. A positive surgical margin was observed in one patient (7.7%), and none experienced major perioperative complications, defined as Clavien–Dindo classification ≥3. The median postoperative length of stay was 8 days (IQR, 8–8.5).

Conclusions

This was the first study to focus on RARP using the Hugo™ RAS system in Japan. Although further investigations should be conducted to assess the long‐term oncological and functional outcomes, the Hugo™ RAS system could provide safe and favorable perioperative outcomes for patients with localized PCa undergoing RARP.
Navigating Physical and Digital Environments: Latin American Video Game Studies in Practice
Authors: Merchant Paul R. , Pitman Thea , King Edward
Published: June 2024

This article reflects on developments in research into Latin American video games two decades after the first studies in the field. In particular, it fills a gap in research by reflecting on the pedagogical uses of video games, focusing both on their value in the undergraduate classroom and on the design of educational games for use by school children, asking to what extent games might afford their players impactful embodied experiences and ways of navigating complex systems of information and power. The case studies centre on the teaching of environmental humanities and digital literacy in a specifically Latin American context.
Microbiota and metabolite alterations in pancreatic head and body/tail cancer patients
Authors: Zhu Yiqing , Liang Xiao , Zhang Guoming , Li Feng , Xu Jianwei , Ma Ruiguang , Chen Xinyu , Ma Miaomiao , Wang Yifan , Chen Changxu , Tang Haoyun , Li Lixiang , Li Zhen
Published: June 2024

Pancreatic head cancer (PHC) and pancreatic body/tail cancer (PBTC) have distinct clinical and biological behaviors. The microbial and metabolic differences in PHC and PBTC have not been studied. The pancreatic microbiota and metabolome of 15 PHC and 8 PBTC tissues and their matched nontumor tissues were characterized using 16S rRNA amplicon sequencing and untargeted metabolomics. At the genus level, Bradyrhizobium was increased while Corynebacterium and Ruminococcus were decreased in the PHC tissues (Head T) compared with the matched nontumor tissues (Head N) significantly. Shuttleworthia, Bacillus, and Bifidobacterium were significantly decreased in the PBTC tissues (Body/Tail T) compared with the matched nontumor tissues (Body/Tail N). Significantly, Ileibacterium was increased whereas Pseudoxanthomonas was decreased in Head T and Body/Tail T, and Lactobacillus was increased in Head T but decreased in Body/Tail T. A total of 102 discriminative metabolites were identified between Head T and Head N, which were scattered through linoleic acid metabolism and purine metabolism pathways. However, there were only four discriminative metabolites between Body/Tail T and Body/Tail N, which were related to glycerophospholipid metabolism and autophagy pathways. The differential metabolites in PHC and PBTC were commonly enriched in alpha‐linolenic acid metabolism and choline metabolism in cancer pathways. Eubacterium decreased in Head T was positively correlated with decreased linoleic acid while negatively correlated with increased arachidyl carnitine and stearoylcarnitine. Bacillus decreased in Body/Tail T was negatively correlated with increased L‐carnitine. These microbiota and metabolites deserve further investigations to reveal their roles in the pathogenesis of PHC and PBTC, providing clues for future treatments.
Unveiling the role of UPF3B in hepatocellular carcinoma: Potential therapeutic target
Authors: Hou Bowen , Shu Min , Liu Chenghao , Du Yunfeng , Xu Cuicui , Jiang Huijiao , Hou Jun , Chen Xueling , Wang Lianghai , Wu Xiangwei
Published: June 2024

RNA‐binding proteins can regulate nucleotide metabolism and gene expression. UPF3B regulator of nonsense mediated mRNA decay (UPF3B) exhibits dysfunction in cancers. However, its role in the progression of hepatocellular carcinoma (HCC) is still insufficiently understood. Here, we found that UPF3B was markedly upregulated in HCC samples and associated with adverse prognosis in patients. UPF3B dramatically promoted HCC growth both in vivo and in vitro. Mechanistically, UPF3B was found to bind to PPP2R2C, a regulatory subunit of PP2A, boosting its mRNA degradation and activating the PI3K/AKT/mTOR pathway. E2F transcription factor 6 (E2F6) directly binds to the UPF3B promoter to facilitate its transcription. Together, the E2F6/UPF3B/PPP2R2C axis promotes HCC growth through the PI3K/AKT/mTOR pathway. Hence, it could be a promising therapeutic target for treating HCC.
Zingiber officinale promotes autophagy and apoptosis in human oral cancer through the C/EBP homologous protein
Authors: Kim Hyun‐Ji , Shin Ji‐Ae , Lee Yeong‐Geun , Jin Bohwan , Lee Won Woo , Lee Yosub , Choi Su‐Jung , Han Jung‐Min , Ahn Min‐Hye , Kim Ji‐Hoon , Park Dong‐Guk , Hong Seong‐Doo , Kang Se‐Chan , Cho Sung‐Dae
Published: June 2024

The rhizome of Zingiber officinale (Z. officinale), commonly known as ginger, has been characterized as a potential drug candidate due to its antitumor effects. However, the chemotherapeutic effect of ginger on human oral cancer remains poorly understood. In this study, we examined the effects of an ethanol extract of Z. officinale rhizomes (ZOE) on oral cancer and identified the components responsible for its pharmacological activity. ZOE exerts its inhibitory activity in oral cancer by inducing both autophagy and apoptosis simultaneously. Mechanistically, ZOE‐induced autophagy and apoptosis in oral cancer are attributed to the reactive oxygen species (ROS)‐mediated endoplasmic reticulum stress response. Additionally, we identified two active components of ZOE, 1‐dehydro‐6‐gingerdione and 8‐shogaol, which were sufficient to stimulate autophagy initiation and apoptosis induction by enhancing CHOP expression. These results suggest that ZOE and its two active components induce ROS generation, upregulate CHOP, initiate autophagy and apoptosis, and hold promising therapeutics against human oral cancer.
Methyltransferase like‐14 suppresses growth and metastasis of non‐small‐cell lung cancer by decreasing LINC02747
Authors: Wang Jiemin , Wang Shu , Yang Haopeng , Wang Ruixuan , Shi Kesong , Liu Yueshi , Dou Le , Yu Haiquan
Published: June 2024

Multiple epigenetic regulatory mechanisms exert critical roles in tumor development, and understanding the interactions and impact of diverse epigenetic modifications on gene expression in cancer is crucial for the development of precision medicine. We found that methyltransferase‐like 14 (METTL14) was significantly downregulated in non‐small‐cell lung cancer (NSCLC) tissues. Functional experiments demonstrated that overexpression of METTL14 inhibited the proliferation and migration of NSCLC cells both in vivo and in vitro, and the colorimetric m6A quantification assay also showed that knockdown of METTL14 notably reduced global m6A modification levels in NSCLC cells. By using the methylated‐RNA immunoprecipitation‐qPCR and dual‐luciferase reporter assays, we verified that long noncoding RNA LINC02747 was a target of METTL14 and was regulated by METTL14‐mediated m6A modification, and silencing LINC02747 inhibited the malignant progression of NSCLC by modulating the PI3K/Akt and CDK4/Cyclin D1 signaling pathway. Further studies revealed that overexpression of METTL14 promoted m6A methylation and accelerated the decay of LINC02747 mRNA via increased recognition of the “GAACU” binding site by YTHDC2. Additionally, histone demethylase lysine‐specific histone demethylase 5B (KDM5B) mediated the demethylation of histone H3 lysine 4 tri‐methylation (H3K4me3) in the METTL14 promoter region and repressed its transcription. In summary, KDM5B downregulated METTL14 expression at the transcriptional level in a H3K4me3‐dependent manner, while METTL14 modulated LINC02747 expression via m6A modification. Our results demonstrate a synergy of multiple mechanisms in regulating the malignant phenotype of NSCLC, revealing the complex regulation involved in the occurrence and development of cancer.
Integrated bioinformatics analysis reveals the bidirectional effects of TSPAN6 for cisplatin resistance in lung cancer
Authors: Fang Zhihong , Bai Jinmei
Published: June 2024

Cisplatin‐based chemotherapy is frequently employed as the primary therapeutic approach for advanced lung cancer. Nevertheless, a significant proportion of patients may develop resistance to cisplatin, leading to diminished efficacy of chemotherapy. Through analysis of Gene Expression Omnibus databases, TSPAN6 has been identified as a key factor in conferring resistance to cisplatin, attributed to its activation of the NF‐κB signaling pathway. Knockdown of TSPAN6 using siRNA resulted in decreased expression levels of NF‐κB in A549 cells. This indicates that TSPAN6 may have dual effects on lung cancer cisplatin resistance and could serve as a promising therapeutic target for individuals with cisplatin resistance.
Dental antibiotic policies, stewardship, and implementation in India: A policy document analysis
Authors: Bhuvaraghan Aarthi , King Rebecca , Walley John , Thiruvenkatachari Badri , Aggarwal Vishal R.
Published: June 2024

Objectives

Dental antibiotic stewardship is crucial in low‐ and middle‐income countries where the burden of antimicrobial resistance (AMR) is high and antibiotic misuse is common. Given that India is the most populous country, the largest antibiotic consumer and has a large dental prescriber population, this study investigated the extent to which current Indian policy and practice for dental antibiotic prescribing and stewardship aligns with the global policy and best practice.

Methods

The READ approach was used to identify and extract data and synthesize the findings. Policy documents on dental antimicrobial stewardship were identified using a systematic search strategy involving nine medical and grey literature databases (Medline, Global Health, Web of Science, Cochrane, CINAHL, Eldis, Global Index Medicus, Proquest and Opengrey), targeted websites (government organizations and dental regulatory bodies) and contact with experts. Framework analysis was used to code extracted data into themes related to dental antimicrobial stewardship.

Results

Of the 3039 records screened, 25 documents were included in the final analysis. The analysis showed a lack of guidelines or toolkits for appropriate antibiotic prescribing in dentistry in India. The treatment guidelines for antimicrobial use in common syndromes published by the Indian Council of Medical Research had no section or content for dental practitioners. Furthermore, the undergraduate dental curriculum developed by the Dental Council of India (DCI), included little content on appropriate antibiotic prescribing and no mention of AMR or stewardship. There were no educational resources either for dental practitioners or patients in the documents.

Conclusion

This document analysis showed that there was little or no mention of dental antibiotic prescribing guidelines in key policy documents such as the National Action Plan on AMR. In addition, contradictory and subjective information provided in some policy documents could encourage dentists and other health professionals such as general practitioners to prescribe antibiotics for common dental conditions for which they are contra‐indicated. There is an urgent need to develop relevant guidelines and include these in Indian policy documents on AMR particularly the National Action Plan on AMR.
Effects of cerebellar repetitive transcranial magnetic stimulation plus physiotherapy in spinocerebellar ataxias – A randomized clinical trial
Authors: Grobe‐Einsler Marcus , Bork Friederike , Faikus Aline , Hurlemann René , Kaut Oliver
Published: June 2024

Background

In absence of drug therapy options, standard treatment for spinocerebellar ataxia consists of symptomatic physiotherapy and speech therapy. New therapeutic options are urgently needed. Transcranial magnetic stimulation is a promising therapeutic option, but applicability is limited by lengthy duration of stimulation protocols.

Methods

In this randomized sham controlled clinical trial, patients were assigned to verum (n = 15) or sham (n = 18) cerebellar transcranial magnetic stimulation. To yield best possible treatment effects, both intervention groups received intensified physiotherapy for the duration of the study.

Results

Ataxia severity was reduced by 1.6 points on the Scale for assessment and Rating of Ataxia among patients in the verum group (p < 0.001). Clinical improvement was significantly larger in the verum group, compared to the sham group (p < 0.01). The treatment effect was mainly carried by improved appendicular coordination. Patients in the verum group also significantly improved in the 8 Meter Walk Test (p < 0.05) and PATA rate (p < 0.01).

Conclusions

Cerebellar rTMS ameliorates ataxia severity in patient with spinocerebellar ataxia. Condensing treatment duration to only 5 days without reduction of treatment effects facilitates applicability and therefore broadens availability to larger patient populations.
Volume loss in the left anterior‐superior subunit of the hypothalamus in amyotrophic lateral sclerosis
Authors: Ghaderi Sadegh , Fatehi Farzad , Kalra Sanjay , Mohammadi Sana , Zemorshidi Fariba , Ramezani Mahtab , Hesami Omid , Pezeshgi Saharnaz , Batouli Seyed Amir Hossein
Published: June 2024

Background and Objective

Amyotrophic lateral sclerosis (ALS) causes motor neuron loss and progressive paralysis. While traditionally viewed as motor neuron disease (MND), ALS also affects non‐motor regions, such as the hypothalamus. This study aimed to quantify the hypothalamic subregion volumes in patients with ALS versus healthy controls (HCs) and examine their associations with demographic and clinical features.

Methods

Forty‐eight participants (24 ALS patients and 24 HCs) underwent structural MRI. A deep convolutional neural network was used for the automated segmentation of the hypothalamic subunits, including the anterior‐superior (a‐sHyp), anterior‐inferior (a‐iHyp), superior tuberal (supTub), inferior tuberal (infTub), and posterior (posHyp). The neural network was validated using FreeSurfer v7.4.1, with individual head size variations normalized using total intracranial volume (TIV) normalization. Statistical analyses were performed for comparisons using independent sample t‐tests. Correlations were calculated using Pearson's and Spearman's tests (p < 0.05). The standard mean difference (SMD) was used to compare the mean differences between parametric variables.

Results

The volume of the left a‐sHyp hypothalamic subunit was significantly lower in ALS patients than in HCs (p = 0.023, SMD = ‐0.681). No significant correlation was found between the volume of the hypothalamic subunits, body mass index (BMI), and ALSFRS‐R in patients with ALS. However, right a‐sHyp (r = 0.420, p = 0.041) was correlated with disease duration, whereas right supTub (r = −0.471, p = 0.020) and left postHyp (r = −0.406, p = 0.049) were negatively correlated with age. There was no significant difference in the volume of hypothalamic subunits between males and females, and no significant difference was found between patients with revised ALS Functional Rating Scale (ALSFRS‐R) scores ≤41 and >41 and those with a disease duration of 9 months or less.

Discussion and Conclusion

The main finding suggests atrophy of the left a‐sHyp hypothalamic subunit in patients with ALS, which is supported by previous research as an extra‐motor neuroimaging finding for ALS.
Identification and validation of COL6A1 as a novel target for tumor electric field therapy in glioblastoma
Authors: Chen Junyi , Liu Yuyang , Lan Jinxin , Liu Hongyu , Tang Qingyun , Li Ze , Qiu Xiaoguang , Hu Wentao , Xie Jiaxin , Feng Yaping , Qin Lilin , Zhang Xin , Liu Jialin , Chen Ling
Published: June 2024

Background

Glioblastoma multiforme (GBM) is the most aggressive primary brain malignancy. Novel therapeutic modalities like tumor electric field therapy (TEFT) have shown promise, but underlying mechanisms remain unclear. The extracellular matrix (ECM) is implicated in GBM progression, warranting investigation into TEFT‐ECM interplay.

Methods

T98G cells were treated with TEFT (200 kHz, 2.2 V/m) for 72 h. Collagen type VI alpha 1 (COL6A1) was identified as hub gene via comprehensive bioinformatic analysis based on RNA sequencing (RNA‐seq) and public glioma datasets. TEFT intervention models were established using T98G and Ln229 cell lines. Pre‐TEFT and post‐TEFT GBM tissues were collected for further validation. Focal adhesion pathway activity was assessed by western blot. Functional partners of COL6A1 were identified and validated by co‐localization and survival analysis.

Results

TEFT altered ECM‐related gene expression in T98G cells, including the hub gene COL6A1. COL6A1 was upregulated in GBM and associated with poor prognosis. Muti‐database GBM single‐cell analysis revealed high‐COL6A1 expression predominantly in malignant cell subpopulations. Differential expression and functional enrichment analyses suggested COL6A1 might be involved in ECM organization and focal adhesion. Western blot (WB), immunofluorescence (IF), and co‐immunoprecipitation (Co‐IP) experiments revealed that TEFT significantly inhibited expression of COL6A1, hindering its interaction with ITGA5, consequently suppressing the FAK/Paxillin/AKT pathway activity. These results suggested that TEFT might exert its antitumor effects by downregulating COL6A1 and thereby inhibiting the activity of the focal adhesion pathway.

Conclusion

TEFT could remodel the ECM of GBM cells by downregulating COL6A1 expression and inhibiting focal adhesion pathway. COL6A1 could interact with ITGA5 and activate the focal adhesion pathway, suggesting that it might be a potential therapeutic target mediating the antitumor effects of TEFT.
Epilepsy alters brain networks in patients with insular glioma
Authors: He Qifeng , Yang Zuocheng , Xue BoWen , Song Xinyu , Zhang Chuanhao , Yin ChuanDong , Li Zhenye , Deng Zhenghai , Sun Shengjun , Qiao Hui , Xie Jian , Hou Zonggang
Published: June 2024

Aims

We intend to elucidate the alterations of cerebral networks in patients with insular glioma‐related epilepsy (GRE) based on resting‐state functional magnetic resonance images.

Methods

We collected 62 insular glioma patients, who were subsequently categorized into glioma‐related epilepsy (GRE) and glioma with no epilepsy (GnE) groups, and recruited 16 healthy individuals matched to the patient's age and gender to form the healthy control (HC) group. Graph theoretical analysis was applied to reveal differences in sensorimotor, default mode, visual, and executive networks among different subgroups.

Results

No significant alterations in functional connectivity were found in either hemisphere insular glioma. Using graph theoretical analysis, differences were found in visual, sensorimotor, and default mode networks (p < 0.05). When the glioma located in the left hemisphere, the degree centrality was reduced in the GE group compared to the GnE group. When the glioma located in the right insula, the degree centrality, nodal efficiency, nodal local efficiency, and nodal clustering coefficient of the GE group were lower than those of the GnE group.

Conclusion

The impact of insular glioma itself and GRE on the brain network is widespread. The networks altered by insular GRE differ depending on the hemisphere location. GRE reduces the nodal properties of brain networks than that in insular glioma.
GIP attenuates neuronal oxidative stress by regulating glucose uptake in spinal cord injury of rat
Authors: Guo Beibei , Qi Mengwei , Luo Xiaoqian , Guo Longyu , Xu Man , Zhang Yufang , Li Zhen , Li Mingxuan , Wu Ronghua , Guan Tuchen , Liu Mei , Liu Yan
Published: June 2024

Aim

Glucose‐dependent insulinotropic polypeptide (GIP) is a ligand of glucose‐dependent insulinotropic polypeptide receptor (GIPR) that plays an important role in the digestive system. In recent years, GIP has been regarded as a hormone‐like peptide to regulate the local metabolic environment. In this study, we investigated the antioxidant role of GIP on the neuron and explored the possible mechanism.

Methods

Cell counting Kit‐8 (CCK‐8) was used to measure cell survival. TdT‐mediated dUTP Nick‐End Labeling (TUNEL) was used to detect apoptosis in vitro and in vivo. Reactive oxygen species (ROS) levels were probed with 2', 7'‐Dichloro dihydrofluorescein diacetate (DCFH‐DA), and glucose intake was detected with 2‐NBDG. Immunofluorescence staining and western blot were used to evaluate the protein level in cells and tissues. Hematoxylin‐eosin (HE) staining, immunofluorescence staining and tract‐tracing were used to observe the morphology of the injured spinal cord. Basso‐Beattie‐Bresnahan (BBB) assay was used to evaluate functional recovery after spinal cord injury.

Results

GIP reduced the ROS level and protected cells from apoptosis in cultured neurons and injured spinal cord. GIP facilitated wound healing and functional recovery of the injured spinal cord. GIP significantly improved the glucose uptake of cultured neurons. Meanwhile, inhibition of glucose uptake significantly attenuated the antioxidant effect of GIP. GIP increased glucose transporter 3 (GLUT3) expression via up‐regulating the level of hypoxia‐inducible factor 1α (HIF‐1α) in an Akt‐dependent manner.

Conclusion

GIP increases GLUT3 expression and promotes glucose intake in neurons, which exerts an antioxidant effect and protects neuronal cells from oxidative stress both in vitro and in vivo.
Advances of the MAPK pathway in the treatment of spinal cord injury
Authors: Huang Shixue , Zhang Yinuo , Shu Haoming , Liu Wei , Zhou Xin , Zhou Xuhui
Published: June 2024

Spinal cord injury (SCI) represents a complex pathology within the central nervous system (CNS), leading to severe sensory and motor impairments. It activates various signaling pathways, notably the mitogen‐activated protein kinase (MAPK) pathway. Present treatment approaches primarily focus on symptomatic relief, lacking efficacy in addressing the underlying pathophysiological mechanisms. Emerging research underscores the significance of the MAPK pathway in neuronal differentiation, growth, survival, axonal regeneration, and inflammatory responses post‐SCI. Modulating this pathway post‐injury has shown promise in attenuating inflammation, minimizing apoptosis, alleviating neuropathic pain, and fostering neural regeneration. Given its pivotal role, the MAPK pathway emerges as a potential therapeutic target in SCI management. This review synthesizes current knowledge on SCI pathology, delineates the MAPK pathway's characteristics, and explores its dual roles in SCI pathology and therapeutic interventions. Furthermore, it addresses the existing challenges in MAPK research in the context of SCI, proposing solutions to overcome these hurdles. Our aim is to offer a comprehensive reference for future research on the MAPK pathway and SCI, laying the groundwork for targeted therapeutic strategies.
Alterations in cortical thickness and volumes of subcortical structures in pediatric patients with complete spinal cord injury
Authors: Wang Ling , Yang Beining , Zheng Weimin , Liang Tengfei , Chen Xin , Chen Qian , Du Jubao , Lu Jie , Li Baowei , Chen Nan
Published: June 2024

Aims

To study the changes in cortical thickness and subcortical gray matter structures in children with complete spinal cord injury (CSCI), reveal the possible causes of dysfunction beyond sensory motor dysfunction after CSCI, and provide a possible neural basis for corresponding functional intervention training.

Methods

Thirty‐seven pediatric CSCI patients and 34 age‐, gender‐matched healthy children as healthy controls (HCs) were recruited. The 3D high‐resolution T1‐weighted structural images of all subjects were obtained using a 3.0 Tesla MRI system. Statistical differences between pediatric CSCI patients and HCs in cortical thickness and volumes of subcortical gray matter structures were evaluated. Then, correlation analyses were performed to analyze the correlation between the imaging indicators and clinical characteristics.

Results

Compared with HCs, pediatric CSCI patients showed decreased cortical thickness in the right precentral gyrus, superior temporal gyrus, and posterior segment of the lateral sulcus, while increased cortical thickness in the right lingual gyrus and inferior occipital gyrus. The volume of the right thalamus in pediatric CSCI patients was significantly smaller than that in HCs. No significant correlation was found between the imaging indicators and the injury duration, sensory scores, and motor scores of pediatric CSCI patients.

Conclusions

These findings demonstrated that the brain structural reorganizations of pediatric CSCI occurred not only in sensory motor areas but also in cognitive and visual related brain regions, which may suggest that the visual processing, cognitive abnormalities, and related early intervention therapy also deserve greater attention beyond sensory motor rehabilitation training in pediatric CSCI patients.
The role of spinal neurons targeted by corticospinal neurons in central poststroke neuropathic pain
Authors: Fan Fenqqi , Yin Tianze , Wu Biwu , Zheng Jiajun , Deng Jiaojiao , Wu Gang , Hu Shukun
Published: June 2024

Background

Central poststroke pain (CPSP) is one of the primary sequelae following stroke, yet its underlying mechanisms are poorly understood.

Methods

By lesioning the lateral thalamic nuclei, we first established a CPSP model that exhibits mechanical and thermal hypersensitivity. Innocuous mechanical stimuli following the thalamic lesion evoked robust neural activation in somatosensory corticospinal neurons (CSNs), as well as in the deep dorsal horn, where low threshold mechanosensory afferents terminate. In this study, we used viral‐based mapping and intersectional functional manipulations to decipher the role of somatosensory CSNs and their spinal targets in the CPSP pathophysiology.

Results

We first mapped the post‐synaptic spinal targets of lumbar innervating CSNs using an anterograde trans‐synaptic AAV1‐based strategy and showed these spinal interneurons were activated by innocuous tactile stimuli post‐thalamic lesion. Functionally, tetanus toxin‐based chronic inactivation of spinal neurons targeted by CSNs prevented the development of CPSP. Consistently, transient chemogenetic silencing of these neurons alleviated established mechanical pain hypersensitivity and innocuous tactile stimuli evoked aversion linked to the CPSP. In contrast, chemogenetic activation of these neurons was insufficient to induce robust mechanical allodynia typically observed in the CPSP.

Conclusion

The CSNs and their spinal targets are required but insufficient for the establishment of CPSP hypersensitivity. Our study provided novel insights into the neural mechanisms underlying CPSP and potential therapeutic interventions to treat refractory central neuropathic pain conditions.
Microvascular recovery with ultrasound in myocardial infarction post‐PCI trial
Authors: Li Shouqiang , Hovseth Chad , Xie Feng , Kadi Soufiane El , Kamp Otto , Goldsweig Andrew Michael , Mathias Wilson , Azevedo Luciene Ferreira , Porter Thomas Richard
Published: June 2024

Purpose

Persistent microvascular obstruction (MVO) after successful percutaneous coronary intervention (PCI) in acute ST segment elevation myocardial infarction (STEMI) has been well‐described. MVO predicts lack of recovery of left ventricular function and increased mortality. Sonothrombolysis utilizing diagnostic ultrasound induced cavitation of commercially available microbubble contrast has been effective at reducing infarct size and improving left ventricular ejection fraction (LVEF) when performed both pre‐ and post‐PCI. However, the effectiveness of post‐PCI sonothrombolysis alone after successful PCI has not been demonstrated.

Methods

A prospective randomized controlled trial was performed in 50 consecutive consenting patients with anterior STEMI who underwent a continuous microbubble infusion immediately following successful PCI. Intermittent high mechanical index (MI) impulses were applied only in the sonthrombolysis group. Delayed enhancement magnetic resonance imaging (MRI) was performed at 48 h and again at 6–8 weeks to assess for differences in infarct size, LVEF, and MVO.

Results

There were no differences between groups in age, gender, and cardiovascular risk factors. Significant (> 2 segments) MVO following successful PCI was observed in 66% of patients. Although sonothrombolysis reduced the extent of MVO acutely, there were no differences in infarct size, LVEF, or extent of MVO by MRI at 48 h. Twenty‐eight patients returned for a follow up MRI at 6–8 weeks. LVEF improved only in the sonothrombolysis group (∆LVEF 7.81 ± 4.57% with sonothrombolysis vs. 1.77 ± 7.02% for low MI only, p = .011).

Conclusion

Post‐PCI sonothrombolysis had minimal effect on reducing myocardial infarct size but improved left ventricular systolic function in patients with acute anterior wall STEMI.
In‐Between Child and World: Educational Responsibility with and against Arendt
Authors: Kloeg Julien , Noordegraaf‐Eelens Liesbeth
Published: June 2024

A key aspect of the educator's responsibility as understood by Hannah Arendt is its dual character. Educators are responsible for both the life and development of the child and the continuance of the world, as Arendt puts it in “The Crisis in Education.” Moreover, these aspects of responsibility are in tension with each other. Arendt's own accounts of responsibility in her political writings are, in a similar way, riddled with tension. What should we conclude from this about the nature of educational responsibility? To address this question, Julien Kloeg and Liesbeth Noordegraaf‐Eelens first reconstruct the meaning of responsibility in Arendt's political writings. They find a broad distinction between political responsibility and personal responsibility: the former consists in contributing to a community (by extension, the world), and the latter in the “two‐in‐one” of silent self‐dialogue. While political responsibility is close to Arendt's description of the responsibility of the educator (for the continuance of the world), personal responsibility does not find an obvious home in her educational thought. From this ambiguous situation of education and Arendt's own theme of the “in‐between” arises the possibility of introducing a concept of educational responsibility that further develops Arendt's position. Kloeg and Noordegraaf‐Eelens's concept of educational responsibility suggests a theory and practice of navigating tensions between conflicting commitments. In their view, this is both an appropriate extension and reform of Arendt's educational work and an insight that does justice to the practical situation of educators in the modern world.