bluuebunny/crossref_metadata_2025 huggingface dataset:
METABOLOMIC PROﬁLING OF ASTROCYTE-GLIOBLASTOMA CELL INTERACTION IN A POSTOPERATIVE TUMOUR MICROENVIRONMENT MODEL
Authors: Kontrimaite Ms Une , McCrorie Dr Phoebe , Porter Mr Harry , Smith Dr Stuart , Kim Dr Dong-Hyun , Rahman Dr Ruman
Published: October 2024

AIMS

Despite multimodal treatment, 9/10 patients diagnosed with isocitrate dehydrogenase wild-type glioblastoma experience tumour recurrence within 5 years. Poor prognosis is in considerable part attributed to the ability of cancer cells to inﬁltrate healthy brain. We hypothesise that metabolic changes underpinning cellular crosstalk between astrocytes and glioblastoma invasive margin cells within a physiologically representative in-vitro tumour microenvironment, may reveal therapeutic targets to prevent or delay glioblastoma recurrence. An initial study aimed to establish baseline metabolomic proﬁles for glioblastoma invasive margin cells and healthy human frontal lobe astrocytes.

METHOD

We used human frontal lobe astrocytes (n=6) and transgenic glioblastoma invasive margin cells tagged with eGFP (n=18) to extract cellular metabolites using biphasic extraction method (methanol:water:chloroform). Liquid Chromatography – Mass Spectrometry (LC-MS) with a ZIC-pHILIC column, coupled to an Orbitrap Mass Spectrometer (Q-Exactive Orbitrap) was used to identify metabolites. Both multivariate and univariate statistical analyses were used to investigate signiﬁcant alterations observed in the metabolic data.

RESULTS

The study uncovered distinct metabolic proﬁles differentiating glioblastoma invasive margin cells from astrocytes. Signiﬁcant alterations were identiﬁed in the alanine, aspartate, and glutamate metabolism pathway, which is required for amino acid synthesis and neurotransmitter balance. Other metabolic pathways include glycine, serine, and threonine metabolism as well as glycerophospholipid metabolism. These preliminary ﬁndings lay the groundwork for further exploration into the cellular interactions in a postoperative tumour microenvironment model and elucidate mechanisms that may contribute to tumour recurrence.

CONCLUSION

Understanding the interactions between cancerous cells and astrocytes is crucial for developing new therapeutic approaches. Our subsequent research will integrate an advanced tumorsphere model composed of a scaffold combining PEGDA hydrogel and an extracellular matrix derived from a decellularized human autopsy brain. This model aims to replicate the postoperative tumour microenvironment more accurately to investigate astrocyte-glioblastoma cell interactions associated with tumour recurrence.
STUDIES ON GLYCOGEN PHOSPHORYLASE AS A POTENTIAL MOLECULAR TARGET IN GLIOBLASTOMA
Authors: Schram Ms Niah , Hayes Dr Joseph , Antia Dr Imeobong , Stasik Dr Izabela
Published: October 2024

AIMS

Glioblastoma (GB) is one of the most aggressive malignancies of the brain and spinal cord. Current standard of care has remained surgical resection of the tumour, followed by radiotherapy and/or chemotherapy. Crucial challenges in the effective treatment of GB include resistance to the main chemotherapeutic, temozolomide. Prognosis is poor with median survival remaining at 14.6 months. A now established hallmark of cancer is the ability of malignant cells to “modify, or reprogram, cellular metabolism”, such as glycolysis upregulation. This hallmark could suggest the potential of targeting a speciﬁc metabolic component within glycolysis, thus reduce energy production, resulting in possible apoptosis/suppressed proliferation. Glycogen phosphorylase (GP), an enzyme in glyconeolysis, could be inhibited for a therapeutic effect in GB. In this project, GP levels across the three different isoforms (PYGB, PYGL, and PYGM) and the effect of the GP inhibitor CP-91149 was investigated across three different GB cell lines.

METHOD

Cell viability of T98G, U251-MG, and U87-MG glioblastoma cell lines and SVGp19 human fetal glial cell line was measured after administration of CP-91149 for 24, 48, and 72 hours. Migration of T98G and U251 cells following treatment with CP-91149 was measured in a wound healing assay. Visualisation of the three GP isoforms was achieved through western blot and conﬁrmed by immunocytochemistry. Flow cytometry was utilized to expand analysis on GP inhibition through assessing cell cycle before and after treatments.

RESULTS

Results showed CP-91149 had a signiﬁcant dose-dependent effect in vitro on all cell lines. Inhibition of GP resulted in reduced cell migration, also in a dose-dependent manner. Western blot and immunocytochemistry analysis showed PYGL is the most predominant isoform of GP.

CONCLUSION

Future work in this project will aim to silence expression of GP in GB cell lines in order to compare the results with that yielded from cells treated with the GP inhibitor CP-91149.
M6A RNA METHYLATION AS A THERAPEUTIC TARGET IN HIGH GRADE GLIOMA
Authors: Radhi Dr Masar , Rowlinson Mr Jonathan , Walker Ms Lauryn , Deacon Dr Simon , Knight Prof Helen , Kim Prof Dong-hyne , Smith Dr Stuart
Published: October 2024

AIMS

High grade glioma (HGG) is a devastating brain cancer that has poor prognostic outcomes. Very recently, the ﬁeld of epitranscriptome has emerged as a novel druggable target for multiple diseases, including cancers. In the present study, we sought to investigate the functional importance of N6-methyladenosine (m6A) RNA methylation in the pathogenesis and drug resistance of paediatric and adult high grade glioma.

METHOD

To identify the expression of key m6A effectors, RT-qPCR and immunoﬂuorescence were undertaken in patient derived HGG cell lines, primary low passage HGG cells and human tissues. The expression of these effectors was modiﬁed using siRNA-mediated knockdown and small molecules to identify their effects on key transcription factors. The consequences of modiﬁcation on the ability of the cells to form neurospheres and invade was also assessed. Developing chemotherapy-resistant cell lines is undertaking to assess the effect of m6A RNA levels on the ability of HGG cells to adapt to environmental changes. Measuring the level of m6A-modiﬁed transcripts were achieved by developing LC-MS/MS and MeRIP (methylated RNA immunoprecipitation) qPCR techniques.

RESULTS

We found that key m6A effectors such as methyltransferase like 3 (METTL3), Wilms tumor 1-associating protein (WTAP) and fat mass and obesity-associated (FTO) are expressed at signiﬁcantly higher level in paediatric and adult HGG models than in control at both gene and protein levels. Furthermore, these effectors regulate the expression of key transcription factors in self-renewal, cell cycle regulation and tumorigenesis. siRNA-mediated depletion of m6A effectors and inhibition of METTL3 using small molecules such as STM2457 and STM3006 reduce the capacity of cells to form neurospheres and invade as well as improving the sensitivity of HGG cells to chemotherapeutic agents.

CONCLUSION

Our ﬁndings suggest that m6A effectors are potential pro-oncogenic factors that, if druggable, will represent an advanced avenue in HGG therapy.
DO NEURO ONCOLOGY PATIENTS FEEL SUﬃCIENTLY SUPPORTED TO MANAGE THEIR SURGICAL WOUNDS AFTER SURGERY?
Authors: Kostick Ms Ellie , Suarez Mr Aeron , Harding Ms Nicola , Hedges Ms Sarah , Sabido Ms Pat , Mullens Ms Laura , Hurwitz Mrs Victoria
Published: October 2024

AIMS

Establish if neuro oncology patients feel they are suﬃciently well supported to manage their wounds post operatively. Is there any correlation to patient wound care management and developing wound infections.

METHOD

There was an anecdotal rise in wound infections in the neuro oncology department, which led to the team investigation a cause. This project was looking to see if patients felt they were suﬃciently supported to manage their wounds post operatively. A survey was sent via email to 94 patient’s who had undergone neurosurgery under the neuro oncology team at a London teaching Hospital in December 2023, January 2024, and February 2024.

RESULTS

There was a response rate of 23.5%. Overall 96% of patients felt able to manage their wound post operatively. 76% of people wished to have the information on wound care at discharge from hospital. 68% advised that they would like to receive information about wound care via printed material and 76% would like verbal instruction with questions. Patients commented that ‘there was a conﬂict of information’, and ‘the information at discharge could have been better’. They would like information on’ how to clean it [the wound]. 3 patients had a suspect infection but did not have treatment, and 1 had a conﬁrmed infection with treatment.

CONCLUSION

Neuro oncology patients are able to manage their wounds post operatively, but they feel that they would beneﬁt from extra support via written material, and verbal instructions. Future projects may include developing an evidence based post operative wound care information leaﬂet and instructions for wound care. Although in this cohort there was only 1 conﬁrmed infection, further investigation is needed to establish the cause for the apparent increase.
MENINGIOMA OEDEMA AND SEIZURES – A META-ANALYSIS
Authors: Tanti Dr Matthew , Nevitt Dr Sarah , Yeo Dr Molly , Bolton Dr William , Chumas Mr Paul , Mathew Mr Ryan , Maguire Dr Melissa
Published: October 2024

AIMS

Meningiomas are primary intracranial neoplasms. Oedema and seizures can occur in the pre and postoperative period and oedema is commonly cited as a risk factor for seizures. A meta-analysis of eight studies published in 2016 identiﬁed preoperative oedema as a risk factor for preoperative seizures. Our aim is to perform an updated review. The literature base has grown and there are studies presenting data on postoperative seizures.

METHOD

The meta-analysis protocol is uploaded to INPLASY (DOI: 10.37766/inplasy2023.7.0101). Existing literature from seven databases was collected and Cochrane guidance was followed. Data was analysed using packages within R programming software. Part of this work was presented in draft form at ILAE 2023 and here we present updated work.

RESULTS

Our search identiﬁed 44 unique studies for meta-analysis. Many studies were biased by subjective oedema measurement or lack of seizure deﬁnition. Preoperative oedema increased the odds of preoperative seizures; odds ratio (OR) 3.41, 95% conﬁdence interval (CI) 3.00 to 3.87, p <.001, studies (k) 24, participants (n) 6,917, low heterogeneity (I2) 0%. There were no subgroup differences by oedema measurement or use of seizure deﬁnition. Preoperative oedema was associated with increased odds of early postoperative seizure (within one week of surgery) but the difference was not signiﬁcant; OR 1.39, CI 0.97-1.99, p =.063, k = 6, n = 2,445, I2 = 0% (low). Preoperative oedema increased the odds of late postoperative seizures; OR 1.95, CI 1.55-2.45, p <.001, k = 7, n = 1,722, I2 = 0% (low). Oedema was associated with seizures following stereotactic radiosurgery in two studies.

CONCLUSION

Preoperative oedema is associated with seizures prior to and following treatment. While there is a positive association between preoperative oedema and early postoperative seizure it is not statistically signiﬁcant.
INTRAOPERATIVE MRI FOR BRAIN TUMOURS: A 15-YEAR RETROSPECTIVE REVIEW AT A SINGLE AUSTRALIAN INSTITUTION
Authors: Madani Dr Daniel , Muralidharan Dr Krishna , Chang Dr Nick , Tang Mr Patrick , Wong Dr Johnny
Published: October 2024

AIMS

Maximal safe resection is the objective of most neuro-oncological operations. The extent of resection can be maximized using imaging updated intraoperatively, including intraoperative MRI (iMRI) theatre, which may translate to improved overall survival. This study aimed to present our 15-year iMRI theatre experience and review its utility.

METHOD

A retrospective cohort analysis was conducted to include all intracranial tumour operations performed in the iMRI theatre (2007–2022). Cases were classiﬁed according to their histopathology: low- and high-grade gliomas (LGG and HGG respectively), meningiomas, pituitary adenomas, and metastases. Demographic, clinical, and histological data was extracted from SurgiNet and analyzed by using the WHO 2021 classiﬁcation. The impact of intraoperative MRI on operative outcomes was reviewed.

RESULTS

A total of 478 neuro-oncology cases were identiﬁed, consisting of 194 pituitary adenomas (n= 69 cases via microscope), 162 HGG, 108 LGG (n= 7 cases for biopsy), 10 cerebral metastases, and 4 meningiomas. Intraoperative MRI theatre utilization averaged 41 cases per year throughout our 15-year experience. The median age was 47 years old (range 35-59 yo.) with a slight predominance in the female population (n= 298, 52%). We identiﬁed 85 (17.8%) re-do cases, which include: pituitary adenoma (n= 15, 17.6%), glioma (n= 68, 80%), and intracranial metastasis (n= 2, 2.4%). Of the 10 intracranial metastases, melanoma consisted of 5, lung carcinoma of 3, and renal cell- and colorectal-carcinoma represented 1 case, respectively. Intraoperative MRI conﬁrmed complete resection in all meningioma cases.

CONCLUSION

In this series, iMRI has been utilised mostly for pituitary adenoma resection and gliomas. It provides near realtime intraoperative navigation and imaging to maximise the extent of resection, prevent injury to important structures and improve patient outcomes in tumour resections.
A NEW INTERNATIONAL ACCELERATOR PROGRAMME FOR NOVEL BRAIN TUMOUR THERAPIES
Authors: Aitken Dr Charlotte , Huskens Dr Nicky , Bushby Prof Katie , Noble Dr Karen , Hamerilk Prof Petra , Kaye Dr Edward , Kobayashi Dr Dione , Mathew Mr Ryan , McCall Dr John , Nazarian Dr Javad , Plummer Prof Ruth , Rahman Dr Ruman , Lopez Dr Juanita , Nagaraju Prof Kanneboyina
Published: October 2024

AIMS

Developing a comprehensive translational programme for brain tumours involves navigating numerous challenges, including preclinical study robustness, safety, clinical trial design, understanding and addressing regulatory requirements, and commercialisation. Recognising the diﬃculty of this journey, the Brain Tumour Research Novel Therapeutics Accelerator (BTR-NTA) was launched in 2023. The BTR-NTA is an accelerator programme providing independent expert guidance to de-risk drug or device development through systematic evaluation. The international, multidisciplinary BTR-NTA Committee spans expertise across the entire therapeutic development pathway. Supported by Brain Tumour Research, BTR-NTA is free for academics and available at nominal cost for industry.

METHOD

Researchers at any stage of therapeutic development may apply to BTR-NTA. Accepted applicants proceed as follows: 1. Applicants complete a form highlighting their current and prospective data and ﬁndings. All materials are covered under a conﬁdentiality agreement that protects their intellectual property; 2. Applicants’ proposals are reviewed by the BTR-NTA Committee; 3. The Applicants and BTR-NTA Committee meet in-person to constructively evaluate the work; and 4. Applicants receive a comprehensive report with feedback on strengths, identiﬁcation of potential risks, and guidance on next steps. The BTR-NTA Committee dedicates time for in-person meetings with each applicant, and extensive time pre and post-meeting.

RESULTS

Since the launch of BTR-NTA, 13 international groups have applied to the programme and three groups have had their therapies reviewed in-person by the BTR-NTA committee to date. Of the groups who provided feedback on the programme, 100% intended to adjust or reﬁne their future work based on the BTR-NTA Committee’s input and the average rating of the programme’s helpfulness was 9.5/10.

CONCLUSION

The ultimate goal of BTR-NTA is to help researchers with a potential therapy for brain tumours navigate the development journey and reach the clinic in an eﬃcient way. This programme will support development of novel therapies to improve outcomes for brain tumour patients.
USING CCA-MRI TO PREDICT RESPONSE TO STEREOTACTIC RADIOSURGERY IN PATIENTS WITH BRAIN METASTASES
Authors: de Boisanger Dr James , Henderson Ms Julia , Guo Mr Yifan , Blackledge Dr Matthew , Harris Dr Emma , Benjamin Dr Philip , Mackinnon Dr Andrew , Rich Dr Philip , Brewer Mr Martin , Solda Dr Francesca , Creak Dr Antonia , Welsh Dr Liam , Rosenfelder Dr Nicola
Published: October 2024

AIMS

Brain metastases (BMs) from different primary cancers may have different radiosensitivity, for example melanoma and renal cell cancers are considered more radioresistant. Radiosensitivity is determined by the intrinsic radiobiological properties of tumours, which include vascularisation and oxygenation. Contrast Clearance Analysis (CCA)-MRI measures delayed contrast behaviour to offer a window into tumour vascularity. The CCA colour map shows areas of contrast accumulation (red), suggesting vascular damage, and rapid contrast clearance (blue), suggesting intact and increased vasculature. We aim to interrogate CCA-MRIs pre-stereotactic radiosurgery (SRS) for differences in contrast handling between BMs from different primaries.

METHOD

10 patients, with 70 BMs, were included in the study. All had CCA-MRIs pre-SRS as part of their planning-MRIs. Radiotherapy-planning-CT scans were fused with the planning-post-contrast-T1-MRI, with consultant clinical oncologist-approved contoured targets, and the CCA-images. Threshold analysis was performed to obtain proportions of red and blue within the enhancing areas of each tumour.

RESULTS

There was a signiﬁcant difference in the proportion of blue between BMs from different primaries (p=0.0294). In pairwise-comparisons, only the difference between lung and renal was signiﬁcant (mean difference 37.65%, p=0.0390). The difference between the proportion of red was also signiﬁcant overall (p=0.0084) (Figure 2). In pairwise comparisons, renal was signiﬁcantly different from lung, breast and melanoma (mean difference 12.65%, p=0.0161; mean difference 12.97%, p=0.0154; and mean difference 11.29%, p=0.0169, respectively).

CONCLUSION

This study offers a novel insight into the vascularity of BMs from different primaries. Further research to explore if these ﬁndings can explain differential SRS outcomes is underway.
Media, Communication, and Democratic Decline: Thoughts on The Paradox of Democracy
Authors: Lawrence Regina G
Published: October 2024

The Paradox of Democracy: Free Speech, Open Media, and Perilous Persuasion, by Zac Gershberg and Sean Illing, argues that the study of democratic decline is mistakenly focused on reversal. Drawing on media ecology theory and an interpretive reading of media and politics in the Western world, the authors argue that the conditions that allowed liberal democracy to become temporarily dominant have now been disrupted and eroded by the rise of new forms of media and communication. This review article assesses that argument in terms of (1) the central role of media and communication in studying of trajectory of democracy; (2) the empirical contributions of political communication scholarship; and (3) the authors’ call for revitalizing a core liberal institution: the press.
Impact of Ticagrelor vs. Clopidogrel in Patients With Acute Coronary Syndrome Undergoing Left Main Percutaneous Coronary Intervention
Authors: Qiu Miaohan , Zhi Xuehan , Liu Haiwei , Liang Zhenyang , Wang Bin , Xu Kai , Guan Shaoyi , Wang Geng , Wang Xiaozeng , Ma Yingyan , Jing Quanmin
Published: October 2024

Objective:

There is limited evidence regarding the choice of P2Y12 receptor inhibitors as a component of dual antiplatelet therapy (DAPT) in patients with left main (LM) disease undergoing percutaneous coronary intervention (PCI). This study aimed to evaluate long-term clinical outcomes of ticagrelor- vs. clopidogrel-based DAPT strategy in acute coronary syndrome (ACS) patients undergoing LM PCI.

Methods:

This is a post-hoc analysis from a prospective, single-center, real-world PCI registry. A total of 1,163 patients discharged post-ACS who underwent LM PCI and received ticagrelor or clopidogrel between March 2016 and March 2019 were included in the study. The primary endpoint was ischemic events at 12 months, including cardiac death, myocardial infarction, or stroke. Secondary outcomes included all-cause death and Bleeding Academic Research Consortium types 2, 3, and 5, and types 3 and 5 bleeding. Propensity score matching was used to adjust for bias due to confounders between the 2 groups.

Results:

The ticagrelor and clopidogrel groups comprised 529 (45.49%) and 634 (54.51%) patients, respectively. During the follow-up period, ticagrelor significantly reduced the rate of ischemic events compared to clopidogrel before (1.32% (7/529) vs. 3.63% (23/634), P = 0.0136) and after propensity score matching (1.41% (6/425) vs. 4.00% (17/425), P = 0.0201). The rates of all-cause death, Bleeding Academic Research Consortium-defined type 2, 3, and 5 bleeding, and type 3 and 5 bleeding were similar between the ticagrelor group and clopidogrel group before or after propensity score matching adjustment (all P > 0.05).

Conclusion:

Among patients with ACS undergoing LM PCI, ticagrelor use was associated with ischemic events benefit without excessive risk of bleeding at 12 months compared with clopidogrel.
Canonical Transient Receptor Potential (TRPC) Channels in Cardiovascular Pathology and their Modulators
Authors: Rubaiy Hussein N.
Published: October 2024

Ion channels play a crucial role in various aspects of cardiac function, such as regulating rhythm and contractility. As a result, they serve as key targets for therapeutic interventions in cardiovascular diseases. Cell function is substantially influenced by the concentration of free cytosolic calcium (Ca2+) and the voltage across the plasma membrane. These characteristics are known to be regulated by Ca2+-permeable non-selective cationic channels, although our knowledge of these channels is still inadequate. The transient receptor potential (TRP) superfamily comprises of many non-selective cation channels with diverse Ca2+ permeability. Canonical or classical TRP (TRPC) channels are a subgroup of the TRP superfamily that are expressed ubiquitously in mammalian cells.

TRPC channels are multidimensional signalling protein complexes that play essential roles in a variety of physiological and pathological processes in humans, including cancer, neurological disorders, cardiovascular diseases, and others. The objective of this article is to focus on the role that TRPC channels play in the cardiovascular system. The role of TRPC channels will be deeply discussed in cardiovascular pathology. Together, a critical element in developing novel treatments that target TRPC channels is comprehending the molecular mechanisms and regulatory pathways of TRPC channels in related cardiovascular diseases and conditions.
Lymphatic Fistula Treatment: Indocyanine Green Lymphography-guided Microsurgery
Authors: Metz Aaron Antaeus , Steinbacher Johannes , Roka-Palkovits Julia , Huettinger Nina , Tinhofer Ines E. , Tzou Chieh-Han John , Rusli Siti Muyassarah
Published: October 2024

Background:

Lymphatic fistulas are a common complication from surgery or interventional procedures resulting in persistent lymphatic leakage and delayed wound healing. The management of lymphatic fistula remains a subject of debate, ranging from conservative treatment to surgical lymphatic ligation. The implementation of a novel microsurgical approach involving lymphatic fistula ligation and/or lymphovenous anastomosis (LVA) using indocyanine green (ICG) lymphography is expected to decrease occurrence and complications. In this study, we share our experience in treating lymphatic fistula–guided microsurgical treatment.

Methods:

A total of 13 patients from our hospital with persistent lymphatic fistula were enrolled in this retrospective study. Lymphatic fistulas and their leakages were identified and ligated by using ICG lymphography and a surgical microscope. In two cases, additional LVA surgery was performed.

Results:

We were able to precisely identify lymphatic fistulas and treat them in all 13 patients. Lymph ligation was performed in all 13 cases, with additional distal LVA in two cases. In all patients, wound healing occurred following lymphatic ligation, except in one patient due to persistent infection. Patients with a lymphatic fistula were referred to our unit within 3 weeks to 1 year after onset, with an average consultation occurring after 5 months of persistent lymphatic fistula.

Conclusions:

Targeted lymphatic vessel ligation with or without LVA with ICG-guided surgical microscope represents a promising highly efficacious therapy for persistent lymphatic fistula. This technique may accelerate wound healing and reduce hospitalization duration, thus advocating for its preferential use in managing lymphatic fistulas.
Progressive maculopathy in a child resulting from vitreopapillary traction on a congenitally anomalous nerve
Authors: Kennamer-Chapman Ross M. , Jampol Lee M. , Rajagopal Rithwick
Published: October 2024

Purpose:

To present a case of worsening maculopathy and vision loss due to vitreopapillary traction associated with an anomalous optic nerve head in a pediatric patient successfully managed with pars plana vitrectomy.

Methods:

Retrospective case report

Results:

A 13-year-old boy presented with unilateral maculopathy that slowly progressed over a four-year period. As his visual acuity declined, he became increasingly symptomatic. The macular pathology occurred in the setting of vitreopapillary traction overlying multiple congenital optic nerve abnormalities, including a myelinated nerve fiber layer and a Bergmeister papilla. Following pars plana vitrectomy to alleviate the traction, the patient’s macular appearance improved, and his vision slowly recovered to baseline.

Conclusion:

There are limited reports of congenital optic nerve anomalies associated with vitreopapillary traction and maculopathy among any age group. This report illustrates a pediatric case in which removal of traction on the nerve head by pars plana vitrectomy was the key therapeutic intervention to alleviate the maculopathy.
“Sterile hypopyon following pars plana vitrectomy and silicone oil injection”
Authors: Stamoulas Konstantinos , Manzar Haider , Raman Vasant , Chandra Aman
Published: October 2024

Purpose:

To report five cases of post-operative sterile endophthalmitis in patients who underwent pars plana vitrectomy with silicone oil injection for retinal detachment.

Methods:

Review of the medical records of five patients who underwent pars plana vitrectomy with silicone oil injection at Southend University Hospital and the Royal Eye Infirmary, Derriford Hospital for rhegmatogenous or tractional retinal detachment.

Results:

All five patients presented with signs of anterior chamber inflammation exhibiting flare, fibrin and hypopyon in the early or late post-operative period following vitrectomy with silicone oil injection. Treatment with topical antibiotics and steroids was commenced, with rapid resolution of the anterior chamber inflammatory reaction and no further intervention required.

Conclusion:

The use of silicone oil as a tamponade agent for retinal detachment can rarely induce sterile anterior chamber inflammation with signs resembling infectious endophthalmitis. Onset of symptoms, absence of pain and good response to topical steroids can help differentiate between the two entities.
The Use of a Single Risk Assessment Tool for Mortality and Numerous Hospital-Acquired Conditions
Authors: Wang Erwin , Samaroo Aditya , Weisstuch Joseph , Rudy Bret
Published: October 2024

Quality assessment organizations leverage numerous patient safety measures to evaluate hospital performance, resulting in significant financial, administrative, and operational burdens on health systems. Low-intensity approaches that allow for reliable risk stratification of patients can reduce the required investment. The Braden score is a routinely performed bedside nursing evaluation validated to assess risk for hospital-acquired pressure injury. We hypothesized that the tool can be used to evaluate risk for other hospital-related adverse outcomes, including mortality, catheter-associated urinary tract infection (CAUTI), and central line–associated bloodstream infection (CLABSI). We found that abnormal Braden scores have significant association with numerous adverse outcome measures, including mortality, CLABSI, CAUTI, and iatrogenic hypoglycemia. Because of its frequency of reevaluation, we have found preliminary evidence that leveraging this tool can reduce harm by quickly identifying the most at-risk patients for various types of iatrogenic harm. We conclude that in the face of increasing automation and technical applications, for example, artificial intelligence–driven tools, highly reliable clinician bedside physical examination and evaluation can still have significant, low-cost, and high-value impact in improving patient safety.
Locally Aggressive and Recurrent Facial Inflammatory Myofibroblastic Tumor in a Pediatric Patient
Authors: Clore Lauren N. , Margulies Ilana G. , Baker Stephen B.
Published: October 2024

Inflammatory myofibroblastic tumor (IMT) is a rare tumor type with a prognosis ranging from benign to locally aggressive. Initially described as a reactive lesion most commonly of the lungs, cases of IMT have now been reported in rare instances in the head and neck, which may be more aggressive than other tumor locations. IMT frequently afflicts children and adolescents, but pediatric cases of IMT in the head and neck region are rare. This report serves to describe a rare presentation of a recurrent and locally aggressive facial IMT in a pediatric patient that required multiple surgical resections alongside medical management.
Sarcomas of the Head and Neck Region
Authors: Dimitrijević Milovan V. , Tomić Ana Marija M. , Todorović Nikola R. , Dimitrijević Ana M. , Kablar Đurđina B.
Published: October 2024

Introduction:

Sarcomas are relatively rare malignant tumors of mesenchymal origin, representing only about 1% of tumors in the head and neck region.

Materials and Methods:

A retrospective study involved patients with sarcomas of the head and neck region who were diagnosed and treated over a 5-year period.

Results:

Nine patients were included, 4 men and 5 women. The mean age of the patients was 51 years. Eight patients had soft tissue sarcomas, and 1 patient had osteosarcoma. The most common histologic types were dermatofibrosarcoma protuberans and angiosarcoma. Tumors presented predominantly with local symptomatology. All patients were treated only by surgical excision. No distant or regional metastases were found in any patient. Complete surgical excision was achieved in all cases, except in patients with chondrosarcoma of the nose and sinuses, who died due to local progression in the second year of follow-up. Other patients were disease-free during the observed period; a patient with osteosarcoma died in the fourth year of follow-up without recurrence of the malignant disease.

Conclusion:

Large prospective and multicenter studies are necessary to provide relevant data on the distribution of different types of sarcoma in the head and neck region, their clinical behavior and response to therapeutic modalities, as well as on recurrence, presence of metastases, and survival.
It doesn't hurt as long as I don't move: Aligning pain assessment in patients with rib fractures with mobilization needed for recovery
Authors: Bauman Zachary M. , Phillips Jakob , Tian Yuqian , Cavlovic Lindsey , Raposo-Hadley Ashley , Khan Hason , Evans Charity H. , Kamien Andrew , Cemaj Samuel , Sheppard Olabisi , Lamb Gina , Veatch Jessica , Matos Mike , Cantrell Emily
Published: October 2024

BACKGROUND

Rib fracture pain is a major issue but likely underappreciated, given that patients avoid activity due to the pain. Pain is one criterion used to determine if someone is a candidate for surgical stabilization of rib fractures (SSRF). The purpose of this study was to assess pain for rib fracture patients, hypothesizing pain from rib fractures is underappreciated in current practice.

METHODS

A prospective study analyzing patients with one or more rib fractures admitted to our Level I trauma center from March 2023 through February 2024. Exclusion criteria included refusal to participate, ventilator dependent, younger than 18 years, moderate/severe traumatic brain injury, spinal cord injury, pregnancy, or incarceration. Basic demographics were obtained. Participants rated their pain on an 11-point Numerical Rating Scale while resting in bed and performing a series of movements (0, no pain; 10, worst pain imaginable). Movements included incentive spirometer, flexion, extension, bilateral side bending, bilateral rotation, and holding a 5-pound dumbbell. Patients undergoing SSRF were surveyed pre- and postoperatively. Outcomes included the difference between pain scores at rest versus performing all movements, difference between pain scores pre- and post-SSRF, and incentive spirometry pre- and postoperatively. Nonparametric analysis was completed with the Wilcoxon signed-rank test with statistical significance set at p < 0.05.

RESULTS

One-hundred two patients were enrolled. The mean age was 60 ± 15 years; 57.8% were male. The median pain score at rest was 3 (interquartile range [IQR], 2–5.5). Pain scores significantly increased to >5 for all movements. Thirty-one patients underwent SSRF. Resting pain prior to SSRF was 3 (IQR, 1–6) and postoperatively was 2 (IQR, 1.5–3) (p = 0.446). For all movements, median Numerical Rating Scale score was significantly less after SSRF (p < 0.001). The median incentive spirometry was 1,100 mL (IQR, 625–1,600 mL) preoperatively and 2,000 mL (IQR, 1,475–2,250 mL) postoperatively.

CONCLUSION

Traditional assessment of pain in patients with rib fractures significantly underappreciates true pain severity caused by movements involving the chest wall and should be considered when evaluating for SSRF.

LEVEL OF EVIDENCE

Therapeutic/Care Management; Level II.
Functional Natural Killer-cell Genetics and Microvascular Inflammation After Kidney Transplantation: An Observational Cohort Study
Authors: Diebold Matthias , Vietzen Hannes , Schatzl Martina , Mayer Katharina A. , Haindl Susanne , Heinzel Andreas , Hittmeyer Philip , Herz Carsten T. , Hopfer Helmut , Menter Thomas , Kühner Laura M. , Berger Sarah M. , Puchhammer-Stöckl Elisabeth , Doberer Konstantin , Steiger Jürg , Schaub Stefan , Böhmig Georg A.
Published: October 2024

Background.

Recent evidence highlights the pivotal role of natural killer (NK) cells in allograft rejection.

Methods.

We explored associations of missing self and gene polymorphisms determining the phenotype and/or functionality of NK cells with microvascular inflammation (MVI) in a single-center cohort of 507 consecutive kidney transplant recipients. Patients were genotyped for killer cell Ig-like receptors and polymorphisms in 4 selected genes (FCGR3A
V/F158 [rs396991], KLRC2
wt/del, KLRK1
HNK/LNK [rs1049174], and rs9916629-C/T).

Results.

MVI was detected in 69 patients (13.6%). In a proportional odds model, the KLRC2
del/del variant reduced MVI risk (odds ratio [OR] 0.26; 95% confidence interval [CI], 0.05-0.93; P = 0.037) independent of donor-specific antibodies, HLA class II eplet mismatch, and number of biopsies. Conversely, missing self (OR 1.40; 95% CI, 1.08-1.80; P = 0.011) and the rs9916629 T/T gene variant increased the risk (OR 1.70; 95% CI, 1.08-2.68; P = 0.021). Graft loss tended to be more frequent among patients with missing self ≥2 (hazard ratio 1.97; 95% CI, 0.89-4.37; P = 0.097), without influence on estimated glomerular filtration trajectories. FCGR3A variants were associated with MVI only in patients with preformed and/or de novo donor-specific antibodies (OR 4.14; 95% CI, 0.99-17.47; P = 0.052).

Conclusions.

Missing self and NK-cell genetics may contribute to MVI, underscoring the important role of NK cells in transplant rejection.
Fractal dimensions for iterated graph systems
Authors: Neroli Ziyu
Published: October 2024

Building upon Li & Britz (Li NZ, Britz T. 2024 On the scale-freeness of random colored substitution networks.
Proc. Amer. Math. Soc
.
152
, 1377–1389 (doi:
10.1090/proc/16604
)), this study aims to introduce fractal geometry into graph theory and to establish a potential theoretical foundation for complex networks. Specifically, we employ the method of substitution to create and explore fractal-like graphs, termed iterated graph systems (IGS) for the first time. While the concept of substitution is commonplace in fractal geometry and dynamical systems, its analysis in the context of graph theory remains a nascent field. By delving into the properties of these systems, including distance and diameter, we derive two primary outcomes. Firstly, within the deterministic IGS, we establish that the Minkowski dimension and Hausdorff dimension align through explicit formulae. Secondly, in the case of random IGS, we demonstrate that almost every Gromov–Hausdorff scaling limit exhibits identical Minkowski and Hausdorff dimensions analytically by their Lyapunov exponents. The exploration of IGS holds the potential to unveil novel directions. These findings not only, mathematically, contribute to our understanding of the interplay between fractals and graphs, but also, physically, suggest promising avenues for applications for complex networks.
The current riboswitch landscape in Clostridioides difficile
Authors: Badilla Lobo Adriana , Soutourina Olga , Peltier Johann
Published: October 2024

Riboswitches are 5′ RNA regulatory elements that are capable of binding to various ligands, such as small metabolites, ions and tRNAs, leading to conformational changes and affecting gene transcription or translation. They are widespread in bacteria and frequently control genes that are essential for the survival or virulence of major pathogens. As a result, they represent promising targets for the development of new antimicrobial treatments. Clostridioides difficile, a leading cause of antibiotic-associated nosocomial diarrhoea in adults, possesses numerous riboswitches in its genome. Accumulating knowledge of riboswitch-based regulatory mechanisms provides insights into the potential therapeutic targets for treating C. difficile infections. This review offers an in-depth examination of the current state of knowledge regarding riboswitch-mediated regulation in C. difficile, highlighting their importance in bacterial adaptability and pathogenicity. Particular attention is given to the ligand specificity and function of known riboswitches in this bacterium. The review also discusses the recent progress that has been made in the development of riboswitch-targeting compounds as potential treatments for C. difficile infections. Future research directions are proposed, emphasizing the need for detailed structural and functional analyses of riboswitches to fully harness their regulatory capabilities for developing new antimicrobial strategies.
Diffuse fibrosis, coronary microvascular dysfunction and systolic dysfunction in Wilson disease
Authors: Steffen Johansson Rebecka , Fogarasi Csenge , Kellman Peter , Kindmark Andreas , Nickander Jannike
Published: October 2024

Background

Wilson disease (WD) causes intracellular copper accumulation in the body due to a genetic defect in the protein ATP7B. Cardiac involvement such as electrocardiographic abnormalities, rhythm abnormalities, heart failure and cardiac death have been reported, however pathophysiological mechanisms remain unclear.

Objectives

This study aimed to comprehensively assess the myocardium in WD patients without cardiac symptoms using multiparametric cardiovascular magnetic resonance imaging (CMR), including quantitative stress perfusion mapping and strain analysis.

Methods

WD patients (n=17, 41±16 years, 47% female) and volunteers (n=17, 39±15 years, 47% female) underwent multiparametric mapping at 1.5 T CMR including cine, native T1, native T2, adenosine stress perfusion mapping, late gadolinium enhancement (LGE), and extracellular volume (ECV) imaging. Symptoms of myocardial ischemia were quantified using Seattle Angina Questionnaire-7 (SAQ-7) and cardiovascular risk factors and medications were recorded.

Results

Both stress perfusion and MPR were lower in WD patients (2.95±0.58 vs 3.67±1.01 ml/min/g, and 3.4±0.8 vs 4.4±1.9), while ECV was higher, (29±3% vs 27±2%), p<0.05 for all. Left ventricular ejection fraction (LVEF) was lower in WD patients, (56±6% vs 61±6%,p=0.02), and LV ventricular global circumferential strain (LV GCS) was higher (-18±2% vs - 20±2%,p=0.005). Late gadolinium enhancement (LGE) was present in the right ventricular insertion point (RVIP) in 12/17 (71%) of the WD patients.

Conclusions

In this small mechanistic study, WD patients on stable treatment without apparent cardiac symptoms have early signs of diffuse fibrosis, coronary microvascular dysfunction (CMD) and systolic dysfunction, shedding light on pathophysiological mechanisms of cardiac dysfunction in copper accumulation.
Radiotherapy triggers pro-angiogenic signaling in human lung
Authors: Soulier Juliette , Curras-Alonso Sandra , Dubail Maxime , Laporte Hugo , Mallick Ayan , Lafouasse Chloé , Colin Delphine , Côté Jean-François , Didier Jérôme , Pouliquen Christelle , Benali Abdelali , Alifano Marco , Durdux Catherine , Damotte Diane , Lefèvre Marine , Bohec Mylène , Cao Kim , Créhange Gilles , Verrelle Pierre , Girard Nicolas , Seguin-Givelet Agathe , Londoño-Vallejo Arturo , Fouillade Charles
Published: October 2024

Radiotherapy is one of the main therapeutic options for the treatment of lung cancer. Although highly efficient, radiation cause severe damages to normal tissue and radio-induced toxicities vary from mild pneumonitis to pulmonary fibrosis. The mechanism leading to these toxicities remain unclear. To investigate the molecular responses of human lung to radiotherapy, we analyzed, by single cell RNAseq, lung tissue resected in the vicinity of the tumor (i.e. treated with radiation) and compared the transcriptional profiles of the distinct lung populations from the same patient removed at distance from the tumor (i.e. non-treated with radiation).

Analysis of six lung samples from patients suffering from Pancoast tumor, a rare lung malignancy that requires neo-adjuvant radiotherapy before surgery, revealed a strong induction of VEGF signaling after radiotherapy. Expression of VEGFA, one of the canonical pro-angiogenic ligands, was found upregulated in multiple cell populations in lung exposed to high doses of radiation. Irradiated capillaries, particularly gCap cells, expressing KDR/VEGFR2, present transcriptional profile similar to tip cells, characterized by sprouting and motility capacities. In addition, we identified a sub-population of alveolar macrophages expressing FLT1/VEGFR1, a receptor for VEGFA, in lung tissues treated by radiotherapy. Cell-Cell communication analysis revealed that FLT1/VEGFR1 positive macrophages interact with tip cells after radiotherapy through IL1B-IL1R signaling. Lastly, analysis of mouse single cell dataset confirmed the increase in the proportion of gCap cells presenting a tip-like phenotype after radiation injury.

Altogether, this study describes, at the single cell level, the pro-angiogenic responses of human lung after radiotherapy. These results will lead to a better understanding of the physiopathology of lung radiation injury and may pave the way to optimize treatments to improve patients’ quality of life.
Comparative assessment of machine learning algorithms to predict severity of disease in COVID-19 patients based on eight cofactors
Authors: Patel Tanvi S. , Patel Daxesh P. , El-Sayed Hoda , Sanyal Mallika , Shrivastav Pranav S.
Published: October 2024

Machine learning is one of the important tools to diagnose and predict the diseased state accurately and effectively. The COVID-19 pandemic caused due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become one of the most researched healthcare topics worldwide. Machine learning algorithms can find efficient and reliable ways to predict the COVID-19 from vast amounts of existing health care data, allowing faster, effective, and more accurate diagnosis with lower risk based on the symptoms. Based on the countrywide data published by the Israeli Ministry of Health, we propose a system that detects COVID-19 instances using simple variables. The COVID-19 dataset used in the study consisted of 278848 patients samples with five different symptoms, namely cough, fever, sore throat, shortness of breath, and headache, apart from other basic information like age, gender, and test indication excluding confirmed COVID-19 result. The data was analyzed using traditional supervised machine learning algorithms namely, Decision tree, Support vector machine, Random Forest, Logistic regression, k-nearest neighbor, and Naive Bayes based on eight cofactors with high accuracy rate (≥ 0.9450). Apart from Support vector machine, all other algorithms displayed better performance based on the AUC score calculated using the receiver operator characteristic (ROC) curve. This study also highlights the significant differences between precision, recall and accuracy for each model.

Abstract Figure

Graphical Abstract
Neuroinflammation and Spinal Cord Pathology Associated with Hypertension in Spontaneously Hypertensive Stroke-Prone Rats
Authors: Noyan H. , Juurlink B.H.J.
Published: October 2024

Hypertension is a major contributor to cardiovascular and cerebrovascular disease, leading to significant central nervous system (CNS) damage, including in the spinal cord. This study examines the spinal cord in uncontrolled hypertension of stroke-prone spontaneously hypertensive rats (SHRsp) compared to normotensive Wistar-Kyoto rats (WKY). Histological analyses, including Sudan Black B staining, NADPH-diaphorase histochemistry, immunohistochemistry, and Western blotting, were used to assess inflammation, gliosis, oxidative stress, and axonal injury.

SHRsp rats displayed extensive spinal cord pathology, including macrophage infiltration, astrocyte hypertrophy, and demyelination. ED1 immunostaining revealed significant microglial activation in SHTsp, particularly in the ventrolateral white matter, while Sudan Black B staining showed edema and lipid-laden macrophages in dilated perivascular spaces. Increased NADPH-diaphorase activity in SHRsp indicated heightened nitric oxide synthase activity. Glial fibrillary acidic protein (GFAP) immunostaining confirmed significant astrogliosis, with hypertrophic astrocytes more prominent in SHRsp. Western blot analysis showed elevated amyloid precursor protein (APP) levels in SHRsp, associated with axonal injury and oxidative stress. APP-positive phagocytes in white matter further suggested active axonal degeneration.

These findings demonstrate significant neuroinflammation, gliosis, and spinal cord tissue damage in hypertensive rats, highlighting the spinal cord’s vulnerability to hypertension. This underscores the importance of addressing hypertensive damage in the CNS, particularly in patients at risk of neurodegenerative or motor impairments.