bluuebunny/crossref_metadata_2025_split huggingface dataset:
The future of postoperative vital sign monitoring in general wards: improving patient safety through continuous artificial intelligence-enabled alert formation and reduction
Authors: Aasvang Eske K. , Meyhoff Christian S. 
Published: October 2023

Purpose
Monitoring of vital signs at the general ward with continuous assessments aided by artificial intelligence (AI) is increasingly being explored in the clinical setting. This review aims to describe current evidence for continuous vital sign monitoring (CVSM) with AI-based alerts − from sensor technology, through alert reduction, impact on complications, and to user-experience during implementation.

Recent findings
CVSM identifies significantly more vital sign deviations than manual intermittent monitoring. This results in high alert generation without AI-evaluation, both in patients with and without complications. Current AI is at the rule-based level, and this potentially reduces irrelevant alerts and identifies patients at need. AI-aided CVSM identifies complications earlier with reduced staff workload and a potential reduction of severe complications.

Summary
The current evidence for AI-aided CSVM suggest a significant role for the technology in reducing the constant 10–30% in-hospital risk of severe postoperative complications. However, large, randomized trials documenting the benefit for patient improvements are still sparse. And the clinical uptake of explainable AI to improve implementation needs investigation.
Update on minimally invasive cardiac surgery and enhanced recovery after surgery
Authors: Salenger Rawn , Lobdell Kevin , Grant Michael C. 
Published: October 2023

Purpose of review
Numerous recent trials have examined the potential benefits of treating cardiac surgery patients with a minimally invasive approach. Recently, Enhanced Recovery After Surgery (ERAS) has also been applied to cardiac surgery, and specifically to minimally invasive cardiac surgery (MICS) patients. This review will explore current evidence regarding MICS, as well as the combination of MICS plus ERAS.

Recent findings
Multiple contemporary prospective and retrospective trials have published data demonstrating equivalent or better outcomes with reduced length of stay (LOS) for MICS patients compared to patients undergoing full sternotomy. In fact, recent reviews and met-analyses suggest that MICS is associated with reduced atrial fibrillation, wound complications, blood transfusion, LOS, and potentially cost. Additionally, several new trials reporting longer term follow-up on MICS coronary and valve surgery have demonstrated durable results. Emerging literature on the benefits of combining MICS and ERAS perioperative protocols have also reported promising results regarding reduced LOS and faster recovery.

Summary
Minimally invasive cardiac surgery appears to provide patients with equivalent or better outcomes, faster recovery, and less surgical trauma compared to full sternotomy. The addition of ERAS phase specific perioperative protocols can help maximize the benefits of MICS.
Neoadjuvant therapy with immune checkpoint inhibitors in operable nonsmall cell lung cancer
Authors: Huber Rudolf M. 
Published: October 2023

Purpose of review
In localized nonsmall cell lung cancer (NSCLC) systemic recurrences after surgery are common. Therefore, adjuvant or neoadjuvant chemotherapy is used. With the advent of immune checkpoint inhibitors (ICIs) in metastatic disease the question is whether ICIs can further improve the outcome.

Recent findings
In several phase I/II trials, major pathological response (MPR) rates with several ICIs between 7% and 50% were seen. No major additional side effects occurred. In combination with chemotherapy CheckMate-816 randomized additional neoadjuvant nivolumab and achieved a high pathological complete response (pCR) rate and a better event-free survival (EFS) – without negatively influencing surgery. More randomized trials are performed with neoadjuvant immunochemotherapy and adjuvant treatment after surgery. In Keynote-671, pembrolizumab is used pre and postoperatively with a significantly higher EFS rate at 2 years (62.4% vs. 40.6%). Similar preliminary results are reported in the AEGEAN (durvalumab) and Neotorch (toripalimab) trials. Higher tumour stage and MPR, partly programmed cell death 1 ligand 1 (PD-L1) expression, tumour mutational burden (TMB) and circulating tumour DNA (ctDNA) are correlated with efficacy.

Summary
Neoadjuvant immunochemotherapy improves MPR and EFS rates, especially in more advanced tumours and tumours expressing PD-L1 – without relevantly increasing toxicities. But further and longer evaluation is needed.
Is there role of adjuvant radiotherapy after complete resection of locally advanced nonsmall cell lung cancer?
Authors: Jiang Liyang , Meng Xiangjiao 
Published: October 2023

Purpose of review
This review aims to provide a timely and relevant overview of the role of postoperative radiotherapy (PORT) in completely resected stage IIIA-N2 nonsmall cell lung cancer (NSCLC). Given the controversy surrounding the use of PORT and the emergence of advanced radiation techniques and therapies, this review provides valuable insight into current and potential treatment strategies.

Recent findings
The Lung ART and PORT-C trials have provided valuable insights into the efficacy of PORT in stage IIIA-N2 NSCLC. While the results have been mixed, studies have shown that advanced radiation techniques, such as intensity-modulated radiotherapy (IMRT) and proton therapy, can reduce cardiopulmonary toxicities associated with PORT. Molecular targeted therapies and immunotherapies have also shown potential in improving NSCLC treatment outcomes.

Summary
The role of radiotherapy becomes smaller and smaller in new era. However, it is too early to abolish radiotherapy for all the patients after complete resection of locally advanced NSCLC. Nowadays, it is recommended to adopt individualized treatment approaches guided by multidisciplinary team consultations. The integration of IMRT, proton therapy, and emerging therapies offers the potential to enhance treatment efficacy while minimizing toxicity. Further research is needed to optimize the use of PORT and explore the method to identify the patients who can really benefit from PORT.
Bivalirudin versus heparin in STEMI after BRIGHT-4 trial: an updated meta-analysis
Authors: Oli Prakash Raj , Shrestha Dhan Bahadur , Shtembari Jurgen , Gyawali Pratik , Regmi Laxmi , Bhandari Amit , Dhungel Swati , Mattumpuram Jishanth , Pant Kailash , Mungee Sudhir 
Published: October 2023

Background
The use of bivalirudin-based anticoagulation over heparin-based anticoagulation for coronary percutaneous intervention has been debated for a long time. Multiple trials have shown promising benefits of bivalirudin over heparin therapy with the most recent addition being the BRIGHT-4 trial. We performed a meta-analysis to assess evidence from these trials, focusing on the coronary intervention of the STEMI population.

Methods
This meta-analysis was performed based on PRISMA guidelines after registering in PROSPERO (CRD42023394701). Databases were searched for relevant articles published before January 2023. Pertinent data from the included studies were extracted and analyzed using RevMan v5.4.

Results
Out of 2375 studies evaluated, 13 randomized control trials with 24 360 acute ST-elevation myocardial infarction patients were included for analysis. The bivalirudin-based anticoagulation reduced the net clinical events (OR 0.75, CI 0.61–0.92), major adverse cardiac or cerebral events (OR 0.85, CI 0.74–0.98), any bleeding (OR 0.61, CI 0.45–0.83), major bleeding (OR 0.54, CI 0.39–0.75), all-cause mortality (OR 0.79, CI 0.67–0.92) and cardiac mortality (OR 0.78, CI 0.65–0.93) significantly without increasing the risk of any stent thrombosis (OR 0.92, 95% CI 0.52–1.61), definite stent thrombosis (OR 1.17, 95% CI 0.62–2.22) and acute stent thrombosis (OR 2.06, 95% CI 0.69–6.09) significantly at 30 days.

Conclusion
Based on this meta-analysis, bivalirudin plus a post-PCI high-dose infusion-based anticoagulation during STEMI PCI has significant benefits over heparin therapy for cardiovascular outcomes without a significant increase in the risk of thrombotic outcomes.
A novel coronary angiographic index for predicting correlation between fractional flow reserve and resting full-cycle ratio
Authors: Ohtani Hirofumi , Ueshima Daisuke , Kawakami Takuya , Hanyu Yoshihiro , Yoshioka Kenji , Mizukami Akira , Matsumura Akihiko , Sasano Tetsuo 
Published: October 2023

Objectives
The discordant results between fractional flow reserve (FFR) and resting full-cycle ratio (RFR) and the influence of angiographic characteristics on their correlation have not been sufficiently investigated. We aimed to identify angiographic characteristics that can predict FFR and RFR correlations using a novel angiographic scoring system.

Methods
This retrospective analysis included 220 patients with 252 intermediate coronary lesions assessed using FFR and RFR. Each branch distal to the target lesion was scored based on the vessel diameter (0 points: < 1.5 mm, 1 point: 1.5–2.0 mm, and 2 points: > 2.0 mm) measured using quantitative coronary angiography. The angiographic score was calculated by adding these scores.

Results
In a propensity score-matched cohort including 84 lesions (42 lesions in each low-and high-angiographic score group), the correlation between FFR and RFR in the high-angiographic score group (>4) was weaker than that in the low-score group (≤4) (Spearman’s correlation: r = 0.44 vs. r = 0.80, P < 0.01). Considering a threshold of functional myocardial ischemia as FFR ≤ 0.80 and RFR ≤ 0.89, the low-angiographic score group showed a significantly lower discordance rate of abnormal FFR/normal RFR than the high-angiographic score group (7.1% vs. 23.8%, P = 0.03), whereas the discordance rates of normal FFR/abnormal RFR were similar in both groups (7.1% vs. 9.5%, P = 0.69).

Conclusion
This retrospective analysis highlights the influence of angiographic characteristics on the correlation between FFR and RFR. Our simple angiographic assessment method may be useful for interpreting physiological evaluations in daily clinical practice.
Development of neural repair therapy for chronic spinal cord trauma: soluble nogo receptor decoy from discovery to clinical trial
Authors: Howard Elisa M. , Strittmatter Stephen M. 
Published: October 2023

Purpose of review
After traumatic spinal cord injury (SCI), neurological deficits persist due to the disconnection of surviving neurons. While repair of connectivity may restore function, no medical therapy exists today.
This review traces the development of the neural repair-based therapeutic AXER-204 from animal studies to the recent clinical trial for chronic cervical SCI.

Recent findings
Molecular studies reveal a Nogo-66 Receptor 1 (NgR1, RTN4R) pathway inhibiting axon regeneration, sprouting, and plasticity in the adult mammalian central nervous system (CNS). Rodent and nonhuman primate studies demonstrate that the soluble receptor decoy NgR(310)ecto-Fc or AXER-204 promotes neural repair and functional recovery in transection and contusion SCI. Recently, this biological agent completed a first-in-human and randomized clinical trial for chronic cervical SCI. The intervention was safe and well tolerated. Across all participants, upper extremity strength did not improve with treatment. However, posthoc and biomarker analyses suggest that AXER-204 may benefit treatment-naïve patients with incomplete SCI in the chronic stage.

Summary
NgR1 signaling restricts neurological recovery in animal studies of CNS injury. The recent clinical trial of AXER-204 provides encouraging signals supporting future focused trials of this neural repair therapeutic. Further, AXER-204 studies provide a roadmap for the development of additional and synergistic therapies for chronic SCI.
Idiopathic intracranial hypertension: expanding our understanding
Authors: Markey Keira , Hutchcroft Christopher , Emsley Hedley 
Published: October 2023

Purpose of reviewIdiopathic intracranial hypertension (IIH) affects predominantly overweight women of childbearing age, causing chronically-disabling headaches and visual loss. Weight loss remains the most effective management strategy, but innovative treatments and randomized control trials (RCTs) remain few. This paper will review recent IIH research.Recent findingsPregnancy-related complications, but not losses, are increased in IIH, while symptom severity is not affected. Weight loss of 24% results in normalization of intracranial pressure (ICP) and improvement in papilledema. Prolonged periods of papilledema result in delayed thinning of the ganglion cell layer. Less-invasive telemetry has improved understanding of the positional effects on ICP with rises seen in the supine and lateral positions. Exenatide, a GLP-1 agonist, may reduce ICP and improve symptoms. Venous sinus stenting is increasingly popular but its benefits over CSF diversion remain unclear.SummaryEarly involvement of obstetric care is recommended with pregnancy in IIH. Early intervention is required to avoid chronic papilledema that confers worse visual outcomes. Positional changes may affect ICP readings. The use of novel ICP telemetric devices has significant potential in future disease monitoring. The dual benefits of weight loss and ICP reduction with exenatide have significant potential in IIH management. Surgical RCTs are still required.
Epilepsy in gliomas: recent insights into risk factors and molecular pathways
Authors: Rudà Roberta , Bruno Francesco , Pellerino Alessia 
Published: October 2023

Purpose of review
The purpose of this review is to discuss the molecular pathways governing the development of seizures in glioma patients.

Recent findings
The intrinsic epileptogenicity of the neuronal component of glioneuronal and neuronal tumors is the most relevant factor for seizure development. The two major molecular alterations behind epileptogenicity are the rat sarcoma virus (RAS)/mitogen-activated protein kinase / extracellular signal-regulated kinase (MAPK/ERK) and phosphatidylinositol-3-kinase / protein kinase B / mammalian target of rapamycin (P13K/AKT/mTOR) pathways. The BRAFv600E mutation has been shown in experimental models to contribute to epileptogenicity, and its inhibition is effective in controlling both seizures and tumor growth. Regarding circumscribed astrocytic gliomas, either BRAFv600E mutation or mTOR hyperactivation represent targets of treatment. The mechanisms of epileptogenicity of diffuse lower-grade gliomas are different: in addition to enhanced glutamatergic mechanisms, the isocitrate dehydrogenase (IDH) 1/2 mutations and their product D2-hydroxyglutarate (D2HG), which is structurally similar to glutamate, exerts excitatory effects on neurons also dependent on the presence of astrocytes. In preclinical models IDH1/2 inhibitors seem to impact both tumor growth and seizures. Conversely, the molecular factors behind the epileptogenicity of glioblastoma are unknown.

Summary
This review summarizes the current state of molecular knowledge on epileptogenicity in gliomas and highlights the relationships between epileptogenicity and tumor growth.
Combination of radiosurgery and immunotherapy in brain metastases: balance between efficacy and toxicities
Authors: Botticella Angela , Dhermain Frederic 
Published: October 2023

Purpose of review
The incidence of brain metastasis is high and still increasing. Among local therapies, stereotactic radiosurgery (SRS) is an effective treatment option, optimally sparing normal brain, even for multiple brain metastases. Immune checkpoint inhibitors (ICIs) become the new standard of care in an increasing number of cancers, and the combination SRS and ICI is often proposed to patients, but few data have been published on the efficacy and the toxicity of this association.

Recent findings
Explaining this lack of consensus: retrospective studies with different primary cancers, various treatment lines and unknown levels of steroid exposure. Concerning the toxicity, the independent association of radionecrosis with brain-PTV volume was confirmed, and a decreased dose of SRS is now tested in a randomized study. Finally, a ‘concurrent’ delivery of SRS and ICI (within a 4 weeks’ interval) seems the optimal schedule; fractionated radiosurgery for large brain metastasis should be favored. Radio-sensitizing nanoparticles and devices aiming to increase the permeability of the blood brain barrier should be considered in future combinations.

Summary
The efficacy/toxicity balance of SRS-ICI combination should be regularly re-evaluated, anticipating continued progress in ICI and SRS delivery, with more long-survivors potentially exposed to long-term toxicities. Patients should be included in clinical trials and clearly informed to participate more closely in the final choice.
Atlantic overturning: new observations and challenges
Authors: Srokosz Meric A. , Holliday N. Penny , Bryden Harry L. 
Published: October 2023

This paper provides an introduction to the special issue of the Philosophical Transactions of the Royal Society of London of papers from the 2022 Royal Society meeting on ‘Atlantic overturning: new observations and challenges'. It provides the background and rationale for the meeting, briefly summarizes prior progress on observing the Atlantic overturning circulation and draws out the new challenges that papers presented at the meeting raise, so pointing the way forward for future research.This article is part of a discussion meeting issue 'Atlantic overturning: new observations and challenges'.
Pathway-based, reaction-specific annotation of disease variants for elucidation of molecular phenotypes
Authors: Orlic-Milacic Marija , Rothfels Karen , Matthews Lisa , Wright Adam , Jassal Bijay , Shamovsky Veronica , Trinh Quang , Gillespie Marc , Sevilla Cristoffer , Tiwari Krishna , Ragueneau Eliot , Gong Chuqiao , Stephan Ralf , May Bruce , Haw Robin , Weiser Joel , Beavers Deidre , Conley Patrick , Hermjakob Henning , Stein Lincoln D. , D’Eustachio Peter , Wu Guanming 
Published: October 2023

AbstractDisease variant annotation in the context of biological reactions and pathways can provide a standardized overview of molecular phenotypes of pathogenic mutations that is amenable to computational mining and mathematical modeling. Reactome, an open source, manually curated, peer-reviewed database of human biological pathways, provides annotations for over 4000 disease variants of close to 400 genes in the context of ∼800 disease reactions constituting ∼400 disease pathways. Functional annotation of disease variants proceeds from normal gene functions, through disease variants whose divergence from normal molecular behaviors has been experimentally verified, to extrapolation from molecular phenotypes of characterized variants to variants of unknown significance using criteria of the American College of Medical Genetics and Genomics (ACMG). Reactome’s pathway-based, reaction-specific disease variant dataset and data model provide a platform to infer pathway output impacts of numerous human disease variants and model organism orthologs, complementing computational predictions of variant pathogenicity.
NFAT5-dependent transcriptional stress control of endothelial cells prevents maladaptive remodeling of pulmonary arterioles in the hypoxic lung
Authors: Laban Hebatullah , Sigmund Sophia , Schlereth Katharina , Brandenburg Lennart , Trogisch Felix A. , Weigert Andreas , De La Torre Carolina , Abukiwan Alia , Mogler Carolin , Hecker Markus , Kuebler Wolfgang M. , Korff Thomas 
Published: October 2023

ABSTRACTAimsChronic hypoxia causes detrimental structural alterations in the lung, which are partially dependent on stress responses of the endothelium. In this context, we revealed that hypoxia-exposed murine lung endothelial cells (MLEC) activate nuclear factor of activated T-cells 5 (NFAT5) - a transcription factor that adjusts the cellular transcriptome to cope with multiple environmental stressors. Here, we studied the functional relevance of NFAT5 for the control of hypoxia-induced transcription in MLEC.Methods and ResultsTargeted ablation ofNfat5in endothelial cells did not evoke phenotypic abnormalities in normoxia-exposed mice. However, MLEC inNfat5-deficient mice up-regulated energy- and protein-metabolism-associated gene expression under normobaric hypoxia (10% O2) for seven days as evidenced by microarray- and scRNA-seq-based analyses. Moreover, loss of NFAT5 boosted the expression and release of platelet-derived growth factor B (Pdgfb)- a HIF1α-regulated driver of vascular smooth muscle cell (VSMC) growth - in capillary MLEC of hypoxia-exposed mice, which was accompanied by exaggerated coverage of distal pulmonary arterioles by VSMC, increased pulmonary vascular resistance and impaired right ventricular functions.In vitro,knockout ofNfat5in cultured MLEC stimulatedPdgfbexpression and release after exposure to hypoxia and amplified binding of HIF1α in thePdgfbpromoter region.ConclusionCollectively, our study identifies NFAT5 as a protective transcription factor required to rapidly adjust the transcriptome of MLEC to hypoxia. Specifically, NFAT5 restricts HIF1α-mediatedPdgfbexpression and consequently limits muscularization and resistance of pulmonary arterioles.HighlightsHypoxia stimulates the transcriptional activity of NFAT5 in MLEC.Loss of NFAT5 in hypoxia-exposed MLEC results in EC subtype-specific maladaption of growth factor-, energy- and protein-metabolism-associated gene expression.Specifically, NFAT5-deficient capillary lung EC unleash HIF1α-regulatedPdgfbexpression and release, which results in excessive coverage of pulmonary arterioles by VSMC.NFAT5-dependent control of early stress responses of capillary MLEC is required to limit the increase in pulmonary vascular resistance and impairment of right ventricular functions.Graphical Abstract
The anti-obesity effect of fish oil in diet-induced obese mice occurs via the induction of heat production in brown but not white adipose tissue
Authors: Obo Takahiko , Hashiguchi Hiroshi , Matsuda Eriko , Kawade Shigeru , Ogiso Kazuma , Iwai Haruki , Ataka Koji , Yasuda Osamu , Arimura Aiko , Deguchi Takahisa , Asakawa Akihiro , Nishio Yoshihiko 
Published: October 2023

AbstractAims/IntroductionThe ω3 polyunsaturated fatty acids in fish oil enhance heat production in adipocytes and exert anti-obesity effects, but the effects of fish oil on heat production in diet-induced obese (DIO) mice are unclear. In this study, we examined whether diets containing fish oil increased the expression of heat-producing genes in adipose tissue and increased body temperature in DIO mice, resulting in weight loss. We also examined fibroblast growth factor 21 (FGF21) levels in blood and the expression of the FGF21 gene in adipose tissue of DIO mice fed fish oil.Materials and MethodsC57BL6/J mice were fed a lard-based high-fat diet for 8 weeks starting at 5 weeks of age and then divided into two groups: one group was fed a fish oil-based high-fat diet, and the other group was fed a lard-based high-fat diet continuously for another 8 weeks. Mice fed a control diet for 16 weeks from the age of 5 weeks served as the control group. Mice were dissected at 21 weeks and used for analysis.ResultsMice fed a fish oil-based high-fat diet lost body weight gain, adipose tissue weight gain, and reduced insulin/leptin resistance. In addition, the rectal temperatures of mice fed a fish oil-based high-fat diet remained higher. The administration of fish oil increased the expression of heat-producing genes in brown adipose tissue (BAT) but did not alter heat-producing genes in inguinal white adipose tissue (WAT). In DIO mice fed a fish oil-based high-fat diet, the FGF21 expression in BAT increased. Furthermore, βklotho expression in BAT increased and the blood FGF21 concentration was decreased compared to mice fed a lard-based high-fat diet.ConclusionsIn DIO mice, fish oil was shown to increase rectal temperature and ameliorate obesity. Furthermore, fish oil enhanced heat production in BAT, but not WAT, in DIO mice.