bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-throughput in vitro drug screening and in vivo studies identify fenretinide as a brain-penetrant DMG therapeutic
Authors: Upton Dannielle H , Liu Jie , George Sandra M , Valvi Santosh , Ung Caitlin , Rayner Benjamin S , Gopalakrishnan Anjana , Pandher Ruby , Khan Aaminah , Venkat Pooja , Mayoh Chelsea , Holliday Holly , Yeung Nicole , Nguyen Hieu , Franshaw Laura , Ehteda Anahid , Shen Han , Farruggia Giovanna , Orienti Isabella , Reynolds C Patrick , Tsoli Maria , Ziegler David S 
Published: February 2025

Abstract

Background
Diffuse midline glioma, characterised by H3K27 alteration (DMG), is the predominant high-grade glioma in children. It commonly originates in the brainstem, yet effective treatments for these patients remain elusive.

Methods
To identify novel therapies for DMG, we conducted high-throughput drug screens (HTS) using biologically active, clinically approved compounds against DMG neurospheres. Multiple primary DMG cultures were utilised in conjunction with in vitro cytotoxicity and clonogenic assays to validate the efficacy of top compounds. Molecularly diverse patient-derived and transgenic DMG orthotopic models were employed to assess therapeutic efficacy alongside pharmacokinetic and immunohistochemical analyses. Mechanistic studies, including RNA sequencing, western blotting, and flow cytometry, were conducted to elucidate the antitumour efficacy of the most promising compound, fenretinide, in DMG cells.

Results
Through HTS, six compounds were identified and validated for their potent cytotoxic activity. However, most of these compounds failed to improve survival in an orthotopic Diffuse Midline Glioma (DMG) model due to limited blood-brain barrier (BBB) penetration. In contrast, fenretinide exhibited effective BBB penetration, significantly enhancing the survival of tumour-bearing animals. Mechanistic studies revealed that fenretinide increased reactive oxygen species (ROS) generation and induced apoptosis by inhibiting PDGFRα. RNA-sequencing further elucidated that fenretinide upregulates the Unfolded Protein Response (UPR) and endoplasmic reticulum (ER) stress pathways while downregulating neurogenesis. The in vivo antitumour efficacy of two fenretinide formulations was demonstrated in PDGFRα-amplified and transgenic DMG models.

Conclusion
This comprehensive study has identified new DMG therapeutic vulnerabilities and highlights fenretinide as a brain-penetrant, anti-DMG agent.
Automated longitudinal treatment response assessment of brain tumors: a systematic review
Authors: Shi Tangqi , Kujawa Aaron , Linares Christian , Vercauteren Tom , Booth Thomas C 
Published: February 2025

Abstract

Background
Longitudinal assessment of tumor burden using imaging helps to determine whether there has been a response to treatment both in trial and real-world settings. From a patient and clinical trial perspective alike, the time to develop disease progression, or progression-free survival, is an important endpoint. However, manual longitudinal response assessment is time-consuming and subject to interobserver variability. Automated response assessment techniques based on machine learning (ML) promise to enhance accuracy and reduce reliance on manual measurement. This paper evaluates the quality and performance accuracy of recently published studies.

Methods
Following PRISMA guidelines and the CLAIM checklist, we searched PUBMED, EMBASE, and Web of Science for articles (January 2010-November 2024). Our PROSPERO-registered study (CRD42024496126) focused on adult brain tumor automated treatment response assessment studies using ML methodologies. We determined the extent of development and validation of the tools and employed QUADAS-2 for study appraisal.

Results
Twenty (including seventeen retrospective and three prospective) studies were included. Data extracted included information on the dataset, automated response assessment including pertinent steps within the pipeline (index tests), and reference standards. Only limited conclusions are appropriate given the high bias risk and applicability concerns (particularly regarding reference standards and patient selection), and the low-level evidence. There was insufficient homogenous data for meta-analysis.

Conclusion
The study highlights the potential of ML to improve brain tumor longitudinal treatment response assessment. Interpretation is limited due to study bias and limited evidence of generalizability. Prospective studies with external datasets validating the latest neuro-oncology criteria are now required.
Dietary intake of whale oil–containing ω‐3 long‐chain polyunsaturated fatty acids attenuates choroidal neovascularization in mice
Authors: Yanai Ryoji , Yasunaga Genta , Tsuji Shunya , Honda Takeshi , Iwata Arihiro , Miyagawa Eiji , Yoshida Koji , Kishimoto Mitsuhiro , Sakai Hiroki , Fujise Yoshihiro , Asagiri Masataka , Mitamura Yoshinori 
Published: February 2025

AbstractAge‐related macular degeneration (AMD) is a leading cause of blindness in Western and developing countries. Since antivascular endothelial growth factor (VEGF) therapy is available for the regression of choroidal neovascularization (CNV), it does not work for the pathophysiology of AMD so a cure is increasingly demanded. Whale oil promotes various bodily functions, such as anti‐inflammatory effects for cardiovascular disease, but its physiological mechanisms are still unclarified. Here, we examined the effects of whale oil on a mouse model of AMD. The area of CNV measured in choroidal flat‐mount preparations at 7 days after laser photocoagulation was significantly smaller in mice fed whale oil compared with control mice free of ω‐3 long‐chain polyunsaturated fatty acids (LCPUFAs). The plasma concentrations of ω‐3 LCPUFAs were higher, whereas those of ω‐6 LCPUFAs were lower in mice fed the diet containing whale oil than in those fed the control diet. The concentrations of various inflammatory cytokines and chemokines in the retina or choroid at 3 or 7 days after CNV induction differed between the two groups of mice. Furthermore, the concentration of VEGF was decreased in the retina but increased in the choroid at 7 or 3 days after photocoagulation, respectively. Our results thus show that dietary intake of whale oil–containing ω‐3 LCPUFAs attenuated CNV in association with changes in inflammatory mediator levels and VEGF expression in the retina and choroid of mice, and it, therefore, warrants further study as a means to protect against AMD in humans.
TMBIM1 ameliorates sepsis‐induced cardiac dysfunction by promoting Parkin‐mediated mitophagy
Authors: Huang Weichang , Lou Anni , Wang Jun , Wang Yuegang , Zhang Wenyong , Li Jierui , Wang Shuanghu , Geng Shiyu , Wang Guozhen , Li Xu 
Published: February 2025

AbstractMyocardial dysfunction is a significant complication of sepsis that is associated with elevated mortality rates. Transmembrane BAX inhibitor motif containing 1 (TMBIM1), a stress‐responsive protein, has garnered interest in the field of cardiovascular disease for its cardioprotective properties. Nevertheless, the role of TMBIM1 on sepsis‐induced cardiac dysfunction (SICD) remains unknown. Here, our findings revealed a significant elevation in TMBIM1 expression within the myocardium following endotoxin challenge and further demonstrate the cardioprotective effects of TMBIM1 through adenovirus‐mediated gene manipulation. Notably, lipopolysaccharide exposure markedly induced mitochondrial dysfunction in cardiomyocytes, which was effectively alleviated by TMBIM1 overexpression, while TMBIM1 knockdown exacerbated this dysfunction. Moreover, in cardiomyocytes subjected to endotoxin challenge, TMBIM1 was observed to interact with Parkin, facilitating its translocation from the cytosol to damaged mitochondria. This interaction enhanced the activation of mitophagy, thereby promoting the clearance of dysfunctional mitochondria and subsequently mitigating cellular injury. Hence, targeting TMBIM1 could be a novel therapeutic strategy for treating SICD.
Vasopressin in traumatic hemorrhagic shock
Authors: Voelckel Wolfgang G. 
Published: February 2025

Purpose of review
Hemorrhage and subsequent development of therapy refractory shock are the major cause of death in potentially salvageable trauma victims. Recent scientific work recognizes that there is an urgent need to develop new life-support strategies. From a variety of interventions and drugs with the potential to prolong the compensation phase or to reverse the decompensation phase of shock, arginine vasopressin (AVP) is one of the most promising and best evaluated drugs. Nonetheless, the efficacy of AVP administration in hemorrhagic shock is still to be proven. Thus, this umbrella review summarizes the current evidence of AVP in hemorrhagic shock.

Recent findings
Fifteen short reviews, narrative reviews, systematic reviews and meta-analysis addressing AVP in traumatic hemorrhagic shock were identified and included in this umbrella review. There is robust evidence deriving form 23 animal studies that AVP administration is effective in hemorrhagic shock, resulting in hemodynamic stabilization and improved survival. This observation is supported by six case reports but not confirmed by two retrospective observational studies and two randomized control trials.

Summary
In uncontrolled hemorrhagic shock, arginine vasopressin might be considered as a therapy of last resort in shock patients not responding to conventional therapy. Further research is needed to determine the potential benefits and optimal dosage/timing of vasopressin use in hemorrhagic shock.
The integration of telehealth in antenatal anesthesia consults
Authors: Scharf Katelyn , Toledo Paloma 
Published: February 2025

Purpose of review
Telehealth is a popular way for health care providers to connect with patients and is utilized by anesthesiologists across the world for preoperative evaluations. The purpose of this review is to outline the latest literature about telehealth use within obstetric anesthesia.

Recent findings
Utilization of telehealth significantly increased during the Coronavirus disease 2019 (COVID-19) pandemic and has proven to be a useful and reliable way to conduct antenatal obstetric anesthesia consultations in high-risk patient groups. Recent publications indicate the reliability and utility of telehealth, especially to reach remote patient populations. This can help anesthesiologists reach patients referred to tertiary centers from remote areas, which can improve the quality and safety of patient care. Furthermore, with hospital-provided infrastructure, the majority of obstetric patients are able to connect with providers via telehealth.

Summary
Obstetric anesthesiologists play a pivotal role in the perioperative planning for high-risk pregnant women, and telehealth can serve as a tool to make this easier and more efficient with high patient and provider satisfaction.
Restoring hemostasis with prothrombin complex concentrate: benefits and risks in trauma-induced coagulopathy
Authors: Grottke Oliver , Heubner Lars 
Published: February 2025

Purpose of this review
To provide evidence for the use of prothrombin complex concentrate (PCC) as a potential hemostatic treatment for trauma-induced coagulopathy with and without anticoagulants.

Recent findings
PCC is effective in enhancing thrombin generation and achieving hemostasis in traumatized patients under anticoagulants. For vitamin K antagonist (VKA) reversal, it shows superior efficacy over fresh frozen plasma, achieving rapid normalization of the international normalized ratio normalization and reduced transfusion needs. In direct oral anticoagulant (DOAC)-associated bleeding, PCC offers an alternative when specific antidotes are unavailable. However, evidence from randomized trials in the field of trauma and coagulopathy is limited, and the results have shown conflicting outcomes in terms of mortality reduction. Further, following PCC application, thromboembolic risks remain a particular concern. Monitoring tools such as thrombin generation assays and point-of-care tests show promise but are not universally available.

Summary
PCC is a valuable option for managing coagulopathy in specific settings, especially VKA and DOAC reversal. Based on current evidence, we caution against the use of PCC as a versatile hemostatic agent suitable for indications involving multiple clotting factor deficiencies for uncontrolled coagulopathic bleeding in trauma or other clinical settings outside anticoagulation reversal. The risk vs. benefit profile should be carefully examined, similar to any other agent.
Outcomes, cost-effectiveness, and ethics in patient blood management
Authors: Bolliger Daniel , Buser Andreas , Tanaka Kenichi A. 
Published: February 2025

Purpose of the review
In this narrative review, we evaluate the recent evidence for benefits, cost-effectiveness, and ethical considerations of patient blood management (PBM) programs.

Recent findings
PBM programs are able to reduce the amount of red blood cell transfusion by 20–40% and the risk of reoperation. Lower morbidity and mortality due to PBM implementation were only shown in retrospective studies with a before-and-after design but not in randomized controlled trials. PBM is very likely to be cost-effective when reduced blood transfusion can be accomplished through low-cost interventions, such as administration of oral iron or antifibrinolytics. Further, cost-efficacy can also be achieved by reducing postoperative morbidity and length of hospital stay. Of note, cost-efficacy of PBM interventions might be better in patients at high bleeding risk. Finally, aiming to improve patient’s outcome while minimizing transfusion-induced complications, PBM seems highly ethical.

Summary
PBM is an important concept as it promotes the rational use of allogeneic blood products and reduces transfusion and wastage of precious and limited blood products.
Update on traumatic brain injury in the ICU
Authors: Slot Rosalinde E.R. , Helbok Raimund , van der Jagt Mathieu 
Published: February 2025

Purpose of review
This review aims to summarize recent developments for the management of severe traumatic brain injury (TBI) in the ICU. Recent advancements in TBI ICU management emphasize a progression toward more multimodal approaches and mitigating secondary brain injury by increased focus on careful systemic management.

Recent findings
Invasive monitoring techniques such as continuous intracranial pressure (ICP) and brain tissue oxygen pressure (PbtO2) monitoring are considered standard of care or may become crucial, respectively, for managing severe TBI. Technological advances in noninvasive techniques (e.g. quantitative pupillometry) are likely to advance our diagnostic and prognostic ability. Blood biomarkers, including glial fibrillary acidic protein, neurofilament light chain, and ubiquitin carboxy-terminal hydrolase L1, provide minimally invasive ways to better assess injury severity and predict outcomes. These advancements support personalized care, which will likely influence clinical management strategies in the future.

Summary
ICP monitoring remains a key component of severe TBI management in ICU. Emerging evidence is slowly changing and improving intensive care and patient outcomes and include both brain-targeted therapies and careful systemic intensive care management.
The utility of wearable devices in the perioperative period
Authors: Xiang Alexander J. , Hu Jenny Xinye , Ladha Karim S. 
Published: February 2025

Purpose of review
Improved perioperative patient monitoring is a crucial step toward better predicting postoperative outcomes. Wearable devices capable of measuring various health-related metrics represent a novel tool that can assist healthcare providers. However, the literature surrounding wearables is wide-ranging, preventing clinicians from drawing definitive conclusions regarding their utility. This review intends to consolidate the recent literature on perioperative wearables and summarize the most salient information.

Recent findings
Wearable devices measuring cardiac output and colonic motility have recently been piloted with mixed results. Novel measurement techniques for established metrics have also been studied, including photoplethysmography devices for heart rate and blood pressure along with resistance thermometers for temperature. Nuanced methods of synthesizing data have been piloted, including machine-learning algorithms for predicting adverse events and trajectory curves for step count progression. Wearable devices are generally well accepted, although adjuvant support systems have improved patient satisfaction.

Summary
Perioperative wearables are valuable tools for tracking postoperative health metrics, predicting adverse events, and improving patient satisfaction. Future research on removing barriers such as technological illiteracy, artifact generation, and false-positive alarms would enable better integration of wearables into the hospital setting.
Personal Public Disclosure: A New Paradigm for Meeting Regulatory Requirements Under Exception From Informed Consent
Authors: Ross Catherine E. , Kleinman Monica E. , Donnino Michael W. 
Published: February 2025

Objectives:
To describe a novel approach to the requirement for public disclosure under regulations for Exception From Informed Consent (EFIC) in an inpatient clinical trial.

Design:
Single-arm intervention study within a clinical trial.

Setting:
Medical and medical/surgical PICUs at an academic children’s hospital.

Participants:
Families of children and young adults younger than 26 years old receiving care in a PICU.

Interventions:
As part of a multipronged approach to meeting requirements for public disclosure for EFIC, we developed and implemented a process termed “personal public disclosure,” in which a member of the study team notifies all potentially eligible patients/families in-person or by phone about the trial as soon as possible upon PICU admission. Patients/families may choose to opt out of future participation in the trial.

Measurements and Main Results:
Over a 16-month period, 1577 potentially eligible patients/families were successfully contacted for personal public disclosure. Of these, 473 (30%) opted out of future participation in the trial. In the same period, 64 patients developed the emergent event of interest for the primary trial. Of these, only 9 (14%) were enrolled. Upon notification of enrollment, all 9 (100%) agreed to continue in the data collection phase of the study. Of the remaining 55 missed enrollments, 38 (69%) were due to the event occurring before personal public disclosure had been completed.

Conclusions:
Personal public disclosure supports patient/family autonomy within an EFIC trial; however, this approach is limited by low cost-effectiveness, feasibility and appropriateness in many circumstances.
External Evaluation of Longitudinal Population Pharmacokinetic Models of Vancomycin in Patients With Osteoarticular Infections
Authors: Nguyen Van Dong , Côté Alice , Marsot Amélie 
Published: February 2025

Background:
Osteoarticular infections pose a challenge for therapeutic drug monitoring of vancomycin because they often require prolonged treatment. Given the extensive renal elimination of vancomycin, its pharmacokinetic properties are difficult to predict in the later stages of treatment because the risk of nephrotoxicity increases with the duration of treatment. In this study, published longitudinal population pharmacokinetic (popPK) models were externally evaluated in a cohort of patients with osteoarticular infections.

Methods:
A literature search was performed in PubMed/EMBASE and published reviews. The predictive performance of the selected models was assessed through prediction- and simulation-based diagnostics using NONMEM software. Data were collected during both the retrospective and prospective phases, during which prospectively recruited patients provided additional vancomycin concentrations.

Results:
The external validation dataset comprised 525 vancomycin concentrations obtained from 73 patients treated for osteoarticular infections at Montréal General Hospital. Two published popPK models that provided different approaches for integrating a longitudinal structure were identified. Both failed to meet the clinically acceptable threshold of imprecision in population predictions. The weighted median absolute prediction error ranged from 34.9% to 48.3% before re-estimation of model parameters and from 33.5% to 35.2% after re-estimation. The re-estimated models tended to underpredict vancomycin concentrations in the later stages of treatment.

Conclusions:
The 2 evaluated models showed poor predictive performance in our local study population. Further studies should explore new strategies to incorporate a longitudinal component and consider other relevant clinical covariates to develop improved longitudinal popPK models for vancomycin.
Reconstruction of Complex Nasal Defect With Anterolateral Thigh Chimeric Flap
Authors: Sơn Trần Thiết , Dung Phạm Thị Việt , Nghĩa Phan Tuấn , Thuý Tạ Thị Hồng , Nhật Phạm Kiến , Anh Hoàng Tuấn 
Published: February 2025

Summary:
Total nasal defects, including adjacent soft tissue damage, present a challenge for plastic surgeons, and in this case, free flaps should be an alternative when local flaps are limited. However, the importance of donor site morbidity must be taken into account for free flaps. Due to flap bulkiness, the anterolateral thigh (ALT) free flaps are less commonly used to restore nasal structures. Our case used a thinned ALT flap to reconstruct the entire nasal defect and part of the upper lip due to the resection of poorly differentiated squamous cell carcinoma. Two ALT flaps were harvested to reconstruct a 10 × 6 cm defect spanning the entire nose and part of the upper lip. Both skin paddles were thinned to a minimum of 4 mm thickness. A costal cartilage graft was used to create a framework for structural support. The donor site was closed with local flaps and skin grafts. No complications were noted during follow-ups. After 24 months, the patient had an excellent nasal contour that matched her skin tone and had no airway obstruction. The thinned ALT chimeric flap can be ideal for large defects composed of multiple anatomical units, even in the facial region. Its advantages are that it is thin, flexible, and well vascularized and can provide favorable aesthetic results with minimal donor site morbidity.
Outcomes of a Tenon Patch Graft for Corneal Perforations in Resolving Infective Keratitis
Authors: Heroor Aniruddh , Dandekar Prajakta , Murthy Somasheila I. 
Published: February 2025

Purpose:
To report the outcomes of a Tenon patch graft (TPG) in sealing corneal perforations in cases with resolving infective keratitis.

Methods:
This retrospective interventional study was conducted at a tertiary eye care center. All patients who underwent a TPG for corneal perforations because of clinically or/and microbiologically diagnosed infective keratitis between 2021 and 2023 were included. The surgical technique was consistent with that used in noninfective etiology. Out of 100 cases undergoing a TPG during the same period, 15 eyes of 14 patients had corneal perforations secondary to infective keratitis.

Results:
The etiological profile included bacterial keratitis in 8, viral and fungal keratitis in 3, and Pythium keratitis in 1 eye of 15 eyes. One patient had bilateral infective keratitis after refractive surgery. The perforations were central in 7 and paracentral in 8 eyes. Successful restoration of tectonic integrity at 1 month was achieved in 14/15 eyes (93%). One patient had a repeat perforation at 3 weeks postoperatively, which was managed with a cyanoacrylate glue application. Infection control was achieved in all cases with adjunctive topical antimicrobial therapy.

Conclusions:
A TPG is a viable option for restoring globe integrity in corneal perforations encountered in resolving infective keratitis.