bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potent drug delivery enhancement of betulinic acid and NVX-207 into equine skin in vitro – a comparison between a novel oxygen flow-assisted transdermal application device and microemulsion gels
Authors: Zscherpe Paula , Kalbitz Jutta , Weber Lisa A. , Paschke Reinhard , Mäder Karsten , von Rechenberg Brigitte , Cavalleri Jessika-M. V. , Meißner Jessica , Klein Karina 
Published: May 2024

Abstract
Background
Gray horses are predisposed to equine malignant melanoma (EMM) with advancing age. Depending on the tumor’s location and size, they can cause severe problems (e.g., defaecation, urination, feeding). A feasible therapy for EMM has not yet been established and surgical excision can be difficult depending on the location of the melanoma. Thus, an effective and safe therapy is needed. Naturally occurring betulinic acid (BA), a pentacyclic triterpene and its synthetic derivate, NVX-207 (3-acetyl-betulinic acid-2-amino-3-hydroxy-2-hydroxymethyl-propanoate) are known for their cytotoxic properties against melanomas and other tumors and have already shown good safety and tolerability in vivo. In this study, BA and NVX-207 were tested for their permeation potential into equine skin in vitro in Franz-type diffusion cell (FDC) experiments after incubation of 5 min, 30 min and 24 h, aiming to use these formulations for prospective in vivo studies as a treatment for early melanoma stages. Potent permeation was defined as reaching or exceeding the half maximal inhibitory concentrations (IC50) of BA or NVX-207 for equine melanoma cells in equine skin samples. The active ingredients were either dissolved in a microemulsion (ME) or in a microemulsion gel (MEG). All of the formulations were transdermally applied but the oil-in-water microemulsion was administered with a novel oxygen flow-assisted (OFA) applicator (DERMADROP TDA).

Results
All tested formulations exceeded the IC50 values for equine melanoma cells for BA and NVX-207 in equine skin samples, independently of the incubation time NVX-207 applied with the OFA applicator showed a significant time-dependent accumulation and depot-effect in the skin after 30 min and 24 h (P < 0.05).

Conclusions
All tested substances showed promising results. Additionally, OFA administration showed a significant accumulation of NVX-207 after 30 min and 24 h of incubation. Further in vivo trials with OFA application are recommended.
Exposure to hyperbaric O2 levels leads to blood-brain barrier breakdown in rodents
Authors: Danino Yehuda M. , Rabinovitz Ricarina , Kirshenboim Inbar , Palzur Eilam , Pick Chaim G. , Ish-Shalom Itamar , Golovkin Yana , Arieli Yehuda 
Published: May 2024

Abstract
Introduction
Hyperbaric oxygen has been used as a medical treatment tool in hyperbaric chambers and is an integral part of professional and combat divers’ activity. In extreme cases, exposure to hyperbaric oxygen can develop central nervous system oxygen toxicity (CNS-OT), which leads to seizures and eventually death. CNS-OT is caused by neuronal hyperactivity due to high oxygen levels, potentially damaging brain cells including the blood-brain barrier (BBB). However, the effect of hyperbaric oxygen levels on the healthy BBB has not been characterized directly yet.

Methods
Six or three different groups of ~ eight rats or mice, respectively, were exposed to increasing levels of partial pressure of oxygen (0.21 to 5 ATA) in a hyperbaric chamber, followed by MRI scanning with gadolinium. Statistical significance (adjusted p-value ≤ 0.05) was assessed using linear regression and ordinary one-way (rats) or two-way (mice) ANOVA with correction of multiple comparison tests. In rats, the effect of 100% oxygen at 5 ATA was independently validated using FITC-Dextran (5 kDa). Statistical significance (p-value ≤ 0.05) was assessed using Welch’s t-test and effect size was calculated by Cohen’s D.

Results
In rats, analyzed MRI scans showed a significant trend of increase in the % gadolinium in brain tissues as a result of hyperbaric oxygen pressures (p-value = 0.0079). The most significant increase was measured at 4 ATA compared to air (adjusted p-value = 0.0461). Significant increased FITC-Dextran levels were measured in the rats’ brains under 100% oxygen at 5 ATA versus air (p-value = 0.0327; Effect size = 2.0). In mice, a significant increase in gadolinium penetration into the hippocampus and frontal cortex was measured over time (adjusted p-value < 0.05) under 100% oxygen at 3 and 5 ATA versus air, and between the treatments (adjusted p-value < 0.0001).

Conclusions
The BBB is increasingly disrupted due to higher levels of hyperbaric oxygen in rodents, indicating a direct relation between hyperbaric oxygen and BBB dysregulation for the first time. We suggest considering this risk in different diving activities, and protocols using a hyperbaric chamber. On the other hand, this study highlights the potential therapeutic usage of hyperbaric oxygen for controlled drug delivery through the BBB into brain tissues in different brain-related diseases.
Robot-assisted thoracoscopic resection of a posterior mediastinal tumor with immunoglobulin G4-related disease: a case report
Authors: Takeuchi Taihei , Takizawa Hiromitsu , Bando Yoshimi , Hosokawa Akio , Sumitomo Hiroyuki , Miyamoto Naoki , Sakamoto Shinichi , Morishita Atsushi , Kawakita Naoya , Toba Hiroaki 
Published: May 2024

Abstract
Background
Immunoglobulin (Ig)G4-related disease affects nearly every organ, and its clinical course varies depending on the involved organ; however, its occurrence in the mediastinum is rarely reported.

Case presentation
A 58-year-old woman presented with a posterior mediastinal tumor along the thoracic spine on imaging. Based on her elevated serum IgG4 level of 349.7 mg/dL, IgG4-related disease was suspected. Since the tumor was growing and malignancy could not be excluded, surgical resection was performed for definitive diagnosis. Robot-assisted thoracoscopic surgery was performed via the left semipronation and right thoracic approaches. The irregularly-shaped tumor was located on the level of the seventh to ninth thoracic vertebra, along the sympathetic nerve. A malignancy was not excluded based on the appearance of the tumor. The tumor had poor mobility. The sympathetic nerves, intercostal arteries, and veins were also excised. In this case, the articulated forceps, used during the robotic surgery, were useful in achieving complete tumor resection along the vertebral body. The pathological examination revealed IgG4-positive plasma infiltration, which fulfilled the criteria for IgG4-related diseases. The postoperative course was uneventful, and the patient underwent follow-up on an outpatient basis without additional medications.

Conclusion
The clinical presentation of IgG4-related disease varies, based on the involved organs. This case was rare because the mediastinum was involved, and it emphasized the effectiveness of surgical resection.
Effect of radiation therapy on lymph node fluorescence in head and neck squamous cell carcinoma after intravenous injection of indocyanine green: a prospective evaluation
Authors: Digonnet Antoine , Vankerkhove Sophie , Moreau Michel , Dekeyser Cécile , Quiriny Marie , Willemse Esther , de saint Aubain Nicolas , Cappello Matteo , Donckier Vincent , Bourgeois Pierre 
Published: May 2024

Abstract
Background
Indocyanine green (ICG)-guided surgery has proven effective in the identification of neoplastic tissues. The effect of radiation therapy (RT) on lymph node fluorescence after intravenous injection of ICG has not been addressed yet. The objective of this study was to evaluate the influence of RT on node fluorescence during neck dissection in head and neck squamous cell carcinoma (HNSCC).

Results
Twenty-four patients with planned neck dissection for HNSCC were prospectively enrolled. Eleven were included without previous radiation therapy and 13 after RT. ICG was intravenously administered in the operating room. The resected specimen was analyzed by the pathology department to determine the status of each resected lymph node (invaded or not). The fluorescence of each resected node was measured in arbitrary units (AU) on paraffin blocs. The surface area (mm2) of all metastatic nodes and of the invaded component were measured. The values of these surface areas were correlated to fluorescence values. A total of 707 nodes were harvested, the mean fluorescence of irradiated nodes (n = 253) was 9.2 AU and of non-irradiated nodes (n = 454) was 9.6 AU (p = 0.63). Fifty nodes were invaded, with a mean fluorescence of 22 AU. The mean fluorescence values in the invaded irradiated nodes (n = 20) and the invaded non-irradiated nodes (n = 30) were 19 AU and 28 AU (p = 0.23), respectively. The surface area of metastatic nodes and of the invaded component were correlated to fluorescence values even after previous RT (p = 0.02).

Conclusion
No differences were observed between the fluorescence of irradiated and non-irradiated lymph nodes, including invaded nodes. ICG-guided surgery can be performed after failed RT.

Trial registration
EudraCT ref. 2013-004498-29, registered 29 November 2013. https://www.clinicaltrialsregister.eu/ctr-search/search?query=2013-004498-29
The prevalence of post traumatic and associated factors among nurses during COVID_19 pandemics: a systematic review and meta-analysis
Authors: Karbasi Afsaneh , Babakhanian Masoudeh , Ahmadzadeh Akram , Omranifard Victoria 
Published: May 2024

Abstract
Background
Despite the negative outcomes, exposure to a crisis may cause people to experience positive changes. This study aims to analyze the prevalence of post-traumatic growth (PTG) and its relevant factors among nurses during the COVID-19 pandemic.

Method
The research protocol was registered with PROSPERO (CRD42022329671), and PRISMA steps were taken in this study. PubMed, Scopus and ProQuest were explored on 1/9/2022 to create the research database. According to the inclusion criterion, all studies analyzing the prevalence of post-traumatic growth through the PTG Inventory were considered eligible. They were all qualitatively assessed through the modified version of the Quality Assessment Checklist for prevalence studies.

Results
A total of 15 papers met the inclusion criterion (n = 22756). According to the research results, the prevalence of PTG was randomly calculated ES [95% Conf. Interval = 0.15 [0.12–0.17]), and heterogeneity was reported I2 = 98.52% (P = 0.000). The results also indicated that the mean score of PTGI decreased in nurses as their work experience and mean age increased. However, the effect was not statistically significant for the mean age (P = 0.06). According to the results, the PTGI score decreased in nurses with more work experience, a finding which was statistically significant (P = 0.04).

Conclusion
This meta-analysis determined a 15% prevalence rate of PTG in nurses. Psychological interventions should be developed and applied to older nurses with more work experience in order to mitigate the harm caused by the pandemic and its consequent crises.
The Clinical Utility of a Tiered Approach to Pediatric Glioma Molecular Characterization for Resource-Limited Settings
Authors: Hammad Rawan , Nobre Liana , Ryall Scott , Arnoldo Anthony , Siddaway Robert , Bennett Julie , Tabori Uri , Hawkins Cynthia 
Published: May 2024

PURPOSE Molecular characterization is key to optimally diagnose and manage cancer. The complexity and cost of routine genomic analysis have unfortunately limited its use and denied many patients access to precision medicine. A possible solution is to rationalize use—creating a tiered approach to testing which uses inexpensive techniques for most patients and limits expensive testing to patients with the highest needs. Here, we tested the utility of this approach to molecularly characterize pediatric glioma in a cost- and time-sensitive manner. METHODS We used a tiered testing pipeline of immunohistochemistry (IHC), customized fusion panels or fluorescence in situ hybridization (FISH), and targeted RNA sequencing in pediatric gliomas. Two distinct diagnostic algorithms were used for low- and high-grade gliomas (LGGs and HGGs). The percentage of driver alterations identified, associated testing costs, and turnaround time (TAT) are reported. RESULTS The tiered approach successfully characterized 96% (95 of 99) of gliomas. For 82 LGGs, IHC, targeted fusion panel or FISH, and targeted RNA sequencing solved 35% (29 of 82), 29% (24 of 82), and 30% (25 of 82) of cases, respectively. A total of 64% (53 of 82) of samples were characterized without targeted RNA sequencing. Of 17 HGG samples, 13 were characterized by IHC and four were characterized by targeted RNA sequencing. The average cost per sample was more affordable when using the tiered approach as compared with up-front targeted RNA sequencing in LGG ($405 US dollars [USD] v $745 USD) and HGGs ($282 USD v $745 USD). The average TAT per sample was also shorter using the tiered approach (10 days for LGG, 5 days for HGG v 14 days for targeted RNA sequencing). CONCLUSION Our tiered approach molecularly characterized 96% of samples in a cost- and time-sensitive manner. Such an approach may be feasible in neuro-oncology centers worldwide, particularly in resource-limited settings.
Real-World Impact of Comprehensive Genomic Profiling on Biomarker Detection, Receipt of Therapy, and Clinical Outcomes in Advanced Non–Small Cell Lung Cancer
Authors: Wallenta Law Jeanna , Bapat Bela , Sweetnam Connor , Mohammed Hina , McBratney Ashleigh , Izano Monika A. , Scannell Bryan Molly , Spencer Scott , Schroeder Brock , Hostin Damon , Simon George R. , Berry Anna B. 
Published: May 2024

PURPOSE Therapeutic decision making for patients with advanced non–small cell lung cancer (aNSCLC) includes a growing number of options for genomic, biomarker-guided, targeted therapies. We compared actionable biomarker detection, targeted therapy receipt, and real-world overall survival (rwOS) in patients with aNSCLC tested with comprehensive genomic profiling (CGP) versus small panel testing (SP) in real-world community health systems. METHODS Patients older than 18 years diagnosed with aNSCLC between January 1, 2015, and December 31, 2020, who received biomarker testing were followed until death or study end (September 30, 2021), and categorized by most comprehensive testing during follow-up: SP (≤52 genes) or CGP (>52 genes). RESULTS Among 3,884 patients (median age, 68 years; 50% female; 73% non-Hispanic White), 20% received CGP and 80% SP. The proportion of patients with ≥one actionable biomarker (actionability) was significantly higher in CGP than in SP (32% v 14%; P < .001). Of patients with actionability, 43% (CGP) and 38% (SP) received matched therapies ( P = .20). Among treated patients, CGP before first-line treatment was associated with higher likelihood of matched therapy in any line (odds ratio, 3.2 [95% CI, 1.84 to 5.53]). CGP testing (hazard ratio [HR], 0.80 [95% CI, 0.72 to 0.89]) and actionability (HR, 0.84 [95% CI, 0.77 to 0.91]) were associated with reduced risk of mortality. Among treated patients with actionability, matched therapy receipt showed improved median rwOS in months in CGP (34 [95% CI, 21 to 49] matched v 14 [95% CI, 10 to 18] unmatched) and SP (27 [95% CI, 21 to 43] matched v 10 [95% CI, 8 to 14] unmatched). CONCLUSION Patients who received CGP had improved detection of actionable biomarkers and greater use of matched therapies, both of which were associated with significant increases in survival.
Endoluminal Sigmoid Sinus Occlusion During Jugular Foramen Tumor Surgery: Novel Technique, Operative Nuances, and Clinical Experience With 33 Patients
Authors: Castillo Andrea L. , Tang Oliver Y. , Gad Steve N. , Park Richard Chan Woo , Ying Yu-Lan Mary , Jyung Robert W. , Liu James K. 
Published: May 2024

BACKGROUND AND IMPORTANCE:
Surgery of jugular foramen tumors (JFTs) often requires vascular control by means of ligating the internal jugular vein and sigmoid sinus (SS) to allow intrabulbar access. Occlusion of the SS traditionally involves presigmoid and retrosigmoid durotomies allowing introduction of ligature devices, predisposing to cerebrospinal fluid (CSF) leakage and pseudomeningoceles. We describe a simple and novel endoluminal sigmoid sinus occlusion (ESSO) technique with Gelfoam that is entirely extradural.

CLINICAL PRESENTATION:
An extended anterolateral infralabyrinthine approach with ESSO was performed in 33 patients with JFTs. After ligating the internal jugular vein, the SS is opened and Gelfoam is placed endoluminally into the proximal SS. Care is taken to avoid occlusion of the venous outflow of the vein of Labbe to avoid temporal lobe venous infarction. Hemostatic gelatin matrix is injected distally to stop venous backflow from the inferior petrosal sinus. The jugular venous system is isolated, and the outer jugular wall can be opened to expose the JFT for resection. There were no complications of temporal lobe venous infarction or postoperative hematoma observed. Four patients with intradural tumor extension developed pseudomeningoceles. For patients with purely extradural JFTs, none developed postoperative incisional CSF leaks and one had pseudomeningocele.

CONCLUSION:
This ESSO technique is fast and effective, permitting occlusion of the SS during JFT surgery. It has the advantage of being entirely extradural, avoiding durotomy which can result in postoperative CSF leak. It is important to keep the Gelfoam distal to the transverse-sigmoid junction to avoid occlusion of the vein of Labbe inlet and temporal lobe venous infarction.
Step 1 for the treatment of periodontal diseases
Authors: Keh Angeline , Yonel Zehra 
Published: May 2024

The association between periodontitis and the dysbiotic biofilm necessitates that patients maintain excellent oral hygiene. Therefore, step 1 of the UK clinical practice guidelines for the treatment of periodontal diseases is aimed at behaviour change and motivation in successful removal of the supragingival dental biofilm and risk-factor control, which involves all the health behavioural change interventions that mitigate recognized risk factors for periodontitis onset and progression (smoking cessation, diabetes management). Step 1 should be tailored for the patient throughout the treatment journey and jointly with clinical findings and medical history. CPD/Clinical Relevance: Step 1 lays the groundwork when progressing through ensuing steps of treatment and can affect response to any periodontal therapy.
Step 2 for the treatment of periodontal diseases
Authors: Shemie Melissa , Shah Mira , Dunn Ian 
Published: May 2024

This article discusses the modalities of treatment involved in step 2 of periodontal therapy, including exploring looking at the evidence-based recommendations produced by the S3 stages I–III periodontal treatment guideline. CPD/Clinical Relevance: Step 2 of periodontal therapy is essential for removal of the subgingival biofilm and reduction in the bacterial load.
Step 3 for the treatment of periodontal diseases: surgical regeneration of the periodontium
Authors: Raindi Devan S , Parmar Jay , Chapple Iain 
Published: May 2024

Surgical regeneration can offer significant benefits in the management of teeth affected by severe periodontitis that continue to demonstrate pocketing following steps 1 and 2 of periodontal therapy. To gain the maximum benefit from this treatment modality, an understanding of the biological principles of regeneration, appropriate case selection and the latest surgical techniques are required. The most recent S3-level guideline released by the European Federation of Periodontology (EFP) and adoloped by the British Society of Periodontology is evidence based, and can support the clinician in such decision-making. CPD/Clinical Relevance: Surgical regenerative techniques can play an important role in the treatment of complex periodontal defects.
DAY-CASE TOTAL ANKLE ARTHROPLASTY
Authors: Drake B. , Blundell M. , Gibson B. , Kingman A. , Kakwani R. , Townshend D. 
Published: May 2024

IntroductionDay Case Surgery (defined as same day discharge) is a priority within the National Health Service and has been shown to provide beneficial outcomes for patients and hospitals. We report our experience developing a Day Case Programme for Total Ankle Replacement (TAR).MethodsPrior to the introduction of a Day Case Programme, average length of stay following TAR in our unit was 3.5 days. Stakeholders were consulted about ways in which same day discharge could be facilitated. Patients' post-operative pain charts were reviewed prior to the introduction of this programme. Inclusion criteria included non-complex surgery (anticipated tourniquet < 2hrs), friend or relative support and pre-operative walking-aid assessment. An enhanced recovery protocol included long-acting popliteal block and dexamethasone. Patients were discharged with opiate analgesia and written pain instructions. Patients were asked to complete a pain and satisfaction questionnaire. Patient Reported Outcome Measures (PROMs) were recorded.ResultsFrom September 2017 to April 2019 21 of 70 patients underwent TAR as a Day Case. Mean age was 67 years (43-85 years). Complications included two delayed wound healings and one representation on day three with urinary retention. No patients reported post-operative nausea or vomiting, 60% did not use Oramorph at home. Average Visual Analogue Score for pain was 23/100 on day one and 21/100 day three post-operatively. There was no significant difference in pre-operative or overall change in MOXFQ, VAS or EQ5D PROMS.ConclusionsEarly results suggest that Day Case Total Ankle Replacements are safe. Appropriate patient selection is necessary. Day Case Surgery relies on support and communication between multiple teams to organise and run effectively.
The efficacy and safety of fluvoxamine in patients with COVID-19: A systematic review and meta-analysis from randomized controlled trials
Authors: Zhou Qiufeng , Zhao Guozheng , Pan Yu , Zhang Ying , Ni Yuehua 
Published: May 2024

Background
Recently, several randomized controlled trials (RCTs) of fluvoxamine have been successfully conducted for the treatment of patients with coronavirus disease 2019 (COVID-19). This systematic review and meta-analysis was to evaluate the efficacy and safety of fluvoxamine in patients with COVID-19.

Methods
MEDLINE, EMBASE, Cochrane Library and clinicaltrials.gov were searched for RCTs which were performed to evaluate fluvoxamine and placebo up to January 31, 2024. Review Manager 5.3 was used to perform meta-analysis. The risk ratio (RR) and mean difference (MD) was analyzed and calculated with a random effect model.

Results
We pooled 4,711 participants from six RCTs (2,382 in the fluvoxamine group and 2,329 in the placebo group). Compared to the placebo group, the fluvoxamine group had a significantly lower rate of clinical deterioration (RR, 0.73; P = 0.004; 95% CI, 0.59 to 0.90; I2 = 0%) and hospitalization (RR, 0.76; P = 0.04; 95% CI, 0.59 to 0.99; I2 = 0%). In the meantime, compared with the placebo group, fluvoxamine group did not show any higher risk of AEs (P = 0.13 and 0.91, respectively) in safety outcomes analysis. The subgroup analysis showed that fluvoxamine treatment performed more than 200 mg daily appears to be more effective than those performed less than 200 mg daily in reducing clinical deterioration and hospitalization risks, while not exhibiting higher AE and SAE risks than placebo group.

Conclusion
Fluvoxamine for patients with COVID-19, especially those who take 200 mg or more daily, is superior to the placebo group in reducing clinical deterioration and hospitalization, and did not show any higher risk of AEs and SAEs in safety concerns, which might be a promising intervention for COVID-19.