bluuebunny/crossref_metadata_2025 huggingface dataset:
Debt and demand regimes in simplified growth models: a comparison of neo-Kaleckian and Supermultiplier models
Authors: Brochier Lídia , Freitas Fabio
Published: October 2023

The paper compares stock-flow consistent (SFC) versions of extended canonical neo-Kaleckian and Supermultiplier models that deal with either households’ or firms’ debt accumulation. This comparison aim is twofold: (i) to evaluate the differences of a debt accumulation process in these models due to their specific closures; (ii) to provide a pedagogical tool for understanding the basic features of each model when dealing with similar issues. In the short run, we find that the relation of debt ratios, demand and growth is similar for both models. In the long run of the Supemultiplier model, only the Minskyan debt regime is economically viable for the firms’ sector. As for the household sector, the paradox of debt is indeed a feature of the canonical Supermultiplier model, yet there may be episodes of rising debt-toincome ratios. As for the neo-Kaleckian model, firms’ leverage ratio can be either pro- or anti-cyclical; in the household sector, the absence of the paradox of debt seems to be the most likely scenario.
Coronary air embolism during transcatheter patent foramen ovale closure for platypnea-orthodeoxia syndrome in a patient with severe respiratory disorder: a case report
Authors: Tanimura Kosuke , Yamamoto Hiroyuki , Hirata Ken-Ichi , Otake Hiromasa
Published: October 2023

Background

Coronary air embolism (CAE) is a rare and life-threatening complication of endovascular procedures, mostly due to procedure-related causes.

Case summary

A 70-year-old man with severe respiratory disorder presented with patent foramen ovale (PFO)-related platypnea-orthodeoxia syndrome (POS). Transcatheter PFO closure was performed under local anaesthesia and intracardiac echocardiographic guidance. After a 5-Fr catheter was passed through the PFO via a 7-Fr femoral vein sheath, the patient suddenly coughed and breathed deeply. Thereafter, intracardiac echocardiography showed massive microbubbles in all cardiac chambers and the ascending aorta, and an electrocardiogram showed ST-segment elevations in the anterior and inferior leads. Emergency coronary angiography confirmed occlusion of the mid-left anterior descending artery, suggesting CAE. As the intracoronary infusion of saline, nitroglycerine, and nicorandil was ineffective, we performed air aspiration using a thrombectomy device, achieving coronary blood flow improvement and ST-segment resolution. Thereafter, positive pressure support using manual bag-valve-mask ventilation under intravenous sedation supported successful transcatheter PFO closure without further air embolization.

Discussion

In this case with severe respiratory dysfunction, spontaneous deep breathing (spontaneous Valsalva manoeuvre) caused negative intrathoracic pressure and large drops in intravascular pressure. This phenomenon might have induced air contamination during device advancement, either by entrapping or leaving residual air in the gaps between the catheter and the sheath. Additionally, PFO with right-to-left shunts is more likely to cause paradoxical air embolization. Thus, the spontaneous Valsalva manoeuvre should be avoided with appropriate respiratory management to prevent paradoxical air embolization, including CAE, during transcatheter PFO closure under local anaesthesia in severe respiratory dysfunction patients.
A dual-process perspective on the relationship between implicit attitudes and discriminatory behaviour
Authors: Tutić Andreas , Grehl Sascha , Liebe Ulf
Published: October 2023

The dual-process perspective (DPP), which contrasts intuitive and deliberative cognitive processes, has advanced our understanding of the conditions under which cultural orientations, such as implicit attitudes, influence overt behaviour considerably. We test a central tenet of the DPP using a choice experiment on the placement of trust in hypothetical economic transactions. According to the principle of catalyzation, the impact of implicit cultural orientations on overt behaviour should be greater if the behaviour comes about in an intuitive rather than a deliberative manner. In this study, we focus on the implicit attitudes towards class and ethnicity and measure their impact on social behaviour via estimates of the effects of corresponding attributes within the choice experiment. Using a framing technique to experimentally induce intuitive or reflective responses, we find that implicit attitudes affect the placement of trust in the intuitive framing condition but not in the reflective framing condition. Besides providing a strict test of a central tenet of the DPP in a choice-experimental set-up, our study also sheds light on different cognitive mechanisms underlying discriminatory behaviour.
A high-quality genome for the slender anole (Anolis apletophallus): an emerging model for field studies of tropical ecology and evolution
Authors: Pirani Renata M , Arias Carlos F , Charles Kristin , Chung Albert K , Curlis John David , Nicholson Daniel J , Vargas Marta , Cox Christian L , McMillan W Owen , Logan Michael L
Published: October 2023

The slender anole, Anolis apletophallus, is a small arboreal lizard of the rainforest understory of central and eastern Panama. This species has been the subject of numerous ecological and evolutionary studies over the past 60 years as a result of attributes that make it especially amenable to field and laboratory science. Slender anoles are highly abundant, short-lived (nearly 100% annual turnover), easy to manipulate in both the lab and field, and are ubiquitous in the forests surrounding the Smithsonian Tropical Research Institute in Panama, where researchers have access to high-quality laboratory facilities. Here, we present a high-quality genome for the slender anole, which is an important new resource for studying this model species. We assembled and annotated the slender anole genome by combining 3 technologies: Oxford Nanopore, 10× Genomics Linked-Reads, and Dovetail Omni-C. We compared this genome with the recently published brown anole (Anolis sagrei) and the canonical green anole (Anolis carolinensis) genomes. Our genome is the first assembled for an Anolis lizard from mainland Central or South America, the regions that host the majority of diversity in the genus. This new reference genome is one of the most complete genomes of any anole assembled to date and should facilitate deeper studies of slender anole evolution, as well as broader scale comparative genomic studies of both mainland and island species. In turn, such studies will further our understanding of the well-known adaptive radiation of Anolis lizards.
When is surgery indicated in metastatic small intestine neuroendocrine tumor?
Authors: Draskacheva Nadica , Saljamovski Darko , Gošić Violeta , Trajkovski Gjorgji , Ristovski Gligor , Misimi Shqipe , Nikolovski Andrej
Published: October 2023

Small intestine neuroendocrine tumors are predominantly small but with high potential for distant metastases development. Diagnosis establishment in early-stage is often difficult and challenging. Small intestine neuroendocrine tumors often initially present with liver metastases. According to the Consensus Guidelines of the North American Neuroendocrine Tumor Society, in patients with liver metastases from unknown origin of primary neuroendocrine tumor, surgical exploration should be performed in order to identify the primary location, prevent small intestine obstruction, and treat one if already present. We present a case of a 69-year-old male patient diagnosed with liver and peritoneal metastases due to small bowel neuroendocrine tumor treated with surgery due to the presence of small intestine obstruction.
The formation channels of multiphase gas in nearby early-type galaxies
Authors: Eskenasy Ryan , Olivares Valeria , Su Yuanyuan , Li Yuan
Published: October 2023

The processes responsible for the assembly of cold and warm gas in early-type galaxies (ETGs) are not well understood. We report on the multiwavelength properties of 15 non-central, nearby (z ≤ 0.008 89) ETGs primarily through Multi-Unit Spectroscopic Explorer (MUSE) and Chandra X-ray observations, to address the origin of their multiphase gas. The MUSE data reveal that 8/15 sources contain warm ionized gas traced by the H α emission line. The morphology of this gas is found to be filamentary in 3/8 sources: NGC 1266, NGC 4374, and NGC 4684, which is similar to that observed in many group and cluster-centred galaxies. All H α filamentary sources have X-ray luminosities exceeding the expected emission from the stellar population, suggesting the presence of diffuse hot gas, which likely cooled to form the cooler phases. The morphologies of the remaining 5/8 sources are rotating gas discs, not as commonly observed in higher mass systems. Chandra X-ray observations (when available) of the ETGs with rotating H α discs indicate that they are nearly void of hot gas. A mixture of stellar mass-loss and external accretion was likely the dominant channel for the cool gas in NGC 4526 and NGC 4710. These ETGs show full kinematic alignment between their stars and gas, and are fast rotators. The H α features within NGC 4191 (clumpy, potentially star-forming ring), NGC 4643, and NGC 5507 (extended structures) along with loosely overlapping stellar and gas populations allow us to attribute external accretion to be the primary formation channel of their cool gas.
How different is the magnetic field at the core–crust interface from that at the neutron star surface? The range allowed in magnetoelastic equilibrium
Authors: Kojima Yasufumi , Yoshida Shijun
Published: October 2023

This study was focused on the investigation of a magnetic field penetrating from the core of a neutron star to its surface. The range of possible field configurations in the intermediate solid crust is less limited owing to the elastic force acting on the force balance. When the Lorentz force is excessively strong, the magnetoelastic equilibrium does not hold, and thus, the magnetic field becomes constrained. By numerically solving for the magnetoelastic equilibrium in a thin crust, the range of the magnetic field at the core–crust interface was determined, while assuming the exterior to be fixed as a dipole in vacuum. The results revealed that the toroidal component should be smaller than the poloidal component at the core–crust interface for the surface dipole, B0 > 2.1 × 1014 G. Consequently, a strong toroidal field, for example, B ∼ 1016 G, as suggested by free precession of magnetars should be confined to a deep interior core and should be reduced to B ∼ 1014 G at the bottom of the crust. The findings of this study provide insights into the interior field structure of magnetars. Further investigations on more complicated geometries with higher multipoles and exterior magnetosphere are necessary.
Simulated non-thermal emission of the supernova remnant G1.9 + 0.3
Authors: Villagran M A , Gómez D O , Velázquez P F , Meyer D M-A , Chiotellis A , Raga A C , Esquivel A , Toledo-Roy J C , Vargas-Rojas K M , Schneiter E M
Published: October 2023

Supernova remnants are the nebular leftover of defunct stellar environments, resulting from the interaction between a supernova blastwave and the circumstellar medium shaped by the progenitor throughout its life. They display a large variety of non-spherical morphologies such as ears that shine non-thermally. We have modelled the structure and the non-thermal emission of the supernova remnant G1.9 + 0.3 through 3D magnetohydrodynamic numerical simulations. We propose that the peculiar ear-shaped morphology of this supernova remnant results from the interaction of its blast wave with a magnetized circumstellar medium, which was previously asymmetrically shaped by the past stellar wind emanating from the progenitor star or its stellar companion. We created synthetic non-thermal radio and X-ray maps from our simulated remnant structure, which are in qualitative agreement with observations, forming ears on the polar directions. Our synthetic map study explains the discrepancies between the measured non-thermal radio and X-ray surface brightness distributions assuming that the inverse Compton process produces the observed X-ray emission.
Feedback-driven anisotropy in the circumgalactic medium for quenching galaxies in the
simba
simulations
Authors: Yang Tianyi , Davé Romeel , Cui Weiguang , Cai Yan-Chuan , Peacock John A , Sorini Daniele
Published: October 2023

We use the simba galaxy formation simulation suite to explore anisotropies in the properties of circumgalactic gas that result from accretion and feedback processes. We particularly focus on the impact of bipolar active galactic nuclei (AGNs) jet feedback as implemented in simba , which quenches galaxies and has a dramatic effect on large-scale gas properties. We show that jet feedback at low redshifts is most common in the stellar mass range (1–5) × 1010 M⊙, so we focus on galaxies with active jets in this mass range. In comparison to runs without jet feedback, jets cause lower densities and higher temperatures along the galaxy minor axis (simba jet direction) at radii $\gtrsim 0.5r_{200c}-4r_{200c}$ and beyond. This effect is less apparent at higher or lower stellar masses, and is strongest within green valley galaxies. The metallicity also shows strong anisotropy out to large scales, driven by star formation feedback. We find substantially stronger anisotropy at $\lesssim 0.5r_{200c}$, but this also exists in runs with no explicit feedback, suggesting that it is due to anisotropic accretion. Finally, we explore anisotropy in the bulk radial motion of the gas, finding that both star formation and AGN wind feedback contribute to pushing the gas outwards along the minor axis at $\lesssim 1$ Mpc, but AGN jet feedback further causes bulk outflow along the minor axis out to several Mpc, which drives quenching via gas starvation. These results provide observational signatures for the operation of AGN feedback in galaxy quenching.
New black hole spin values for Sagittarius A* obtained with the outflow method
Authors: Daly Ruth A , Donahue Megan , O’Dea Christopher P , Sebastian Biny , Haggard Daryl , Lu Anan
Published: October 2023

Six archival Chandra observations are matched with eight sets of radio data and studied in the context of the outflow method to measure and study the spin properties of $\rm {Sgr ~A^{*}}$. Three radio and X-ray data sets obtained simultaneously, or partially simultaneously, are identified as preferred for the purpose of measuring the spin properties of $\rm {Sgr ~A^{*}}$. Similar results are obtained with other data sets. Results obtained with the preferred data sets are combined and indicate weighted mean values of the spin function of $F = 0.62 \pm 0.10$ and dimensionless spin angular momentum of $a_* = 0.90 \pm 0.06$. The spin function translates into measurements of the black hole rotational mass, Mrot, irreducible mass, Mirr, and spin mass–energy available for extraction, Mspin, relative to the total black hole dynamical mass, Mdyn. Weighted mean values of (Mrot/Mdyn) = (0.53 ± 0.06), (Mirr/Mdyn) = (0.85 ± 0.04), (Mspin/Mdyn) = (0.15 ± 0.04), Mrot = (2.2 ± 0.3) × 106 M⊙, Mirr = (3.5 ± 0.2) × 106 M⊙, and Mspin = (6.2 ± 1.6) × 105 M⊙ are obtained; of course (Mrot/Mirr) = (0.62 ± 0.10) since (Mrot/Mirr) = F. Values obtained for $\rm {Sgr ~A^{*}}$ are compared with those obtained for M87 based on the published spin function, which indicate that M87 carries substantially more rotational energy and spin mass–energy relative to the total (i.e. dynamical) black hole mass, the irreducible black hole mass, and in absolute terms.
Assessment of a new sub-grid model for magnetohydrodynamical turbulence – II. Kelvin–Helmholtz instability
Authors: Miravet-Tenés Miquel , Cerdá-Durán Pablo , Obergaulinger Martin , Font José A
Published: October 2023

The modelling of astrophysical systems such as binary neutron star mergers or the formation of magnetars from the collapse of massive stars involves the numerical evolution of magnetized fluids at extremely large Reynolds numbers. This is a major challenge for (unresolved) direct numerical simulations which may struggle to resolve highly dynamical features as, e.g. turbulence, magnetic field amplification, or the transport of angular momentum. Sub-grid models offer a means to overcome those difficulties. In a recent paper we presented MInIT, an MHD-instability-induced-turbulence mean-field, sub-grid model based on the modelling of the turbulent (Maxwell, Reynolds, and Faraday) stress tensors. While in our previous work MInIT was assessed within the framework of the magnetorotational instability, in this paper we further evaluate the model in the context of the Kelvin–Helmholtz instability (KHI). The main difference with other sub-grid models (as e.g. the alpha-viscosity model or the gradient model) is that in MInIT, we track independently the turbulent energy density at sub-grid scales, which is used, via a simple closure relation, to compute the different turbulent stresses relevant for the dynamics. The free coefficients of the model are calibrated using well-resolved box simulations of magnetic turbulence generated by the KHI. We test the model against these simulations and show that it yields order-of-magnitude accurate predictions for the evolution of the turbulent Reynolds and Maxwell stresses.
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.

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.

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.

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.

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.
LPIN2-related Majeed syndrome: report of two Indian patients with novel variants in LPIN2 and review of literature
Authors: Badiger Vaishnavi Ashok , Balan Suma , Madan Sumanth , Gogineni Kishore Sai , Shah Hitesh , Narayanan Dhanya Lakshmi
Published: October 2023

LPIN2-related Majeed syndrome (MIM# 609628) is a rare non-inflammasome autoinflammatory disease, caused due to biallelic variants in LPIN2 (MIM* 605519). To date, only 31 individuals from 18 families have been reported with this rare condition. Exome sequencing was done in two affected individuals from two unrelated families. Additionally, phenotypic, and genotypic information from the literature was reviewed. Two novel homozygous missense variants, c.2207G>A p. (Arg736His) and c.1157C>G p. (Ser386Ter) in LPIN2, were identified in family 1 and family 2 respectively. Chronic recurrent osteomyelitis involving the lower extremities was the most common clinical presentation. LPIN2-related Majeed syndrome should be considered as a differential diagnosis in an individual with clinical or radiological evidence of recurrent sterile osteomyelitis and chronic anaemia.
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.

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 review

Idiopathic 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 findings

Pregnancy-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.

Early 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.

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.

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

Disease 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

Aims

Chronic 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 Results

Targeted 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.

Conclusion

Collectively, 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.

Highlights

Hypoxia 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

Aims/Introduction

The 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 Methods

C57BL6/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.

Results

Mice 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.

Conclusions

In 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.
The radiation of Austral teals and the evolution of flightlessness
Authors: Rosinger Hanna S. , Kardialsky Olga , Kennedy Martyn , Spencer Hamish G. , Steiner Florian M. , Schlick-Steiner Birgit C. , Rawlence Nicolas J. , Knapp Michael
Published: October 2023

The origin and evolution in the Southern Hemisphere of the Austral teals, consisting of the grey-teal and brown-teal species complexes, remains poorly understood due to limited molecular data. With the group containing multiple independent examples of flight loss, understanding the evolutionary history of the group is of significant interest for functional genomic studies into the evolution of flightlessness. Here we present the first whole mitogenome-based phylogeny of the Austral teals. We show that the group diverged from a common ancestor with mallards in the late Miocene and soon after radiated into the brown-teal and grey-teal lineages, as well as the widely distributed pintails and green-winged ducks. The brown-teal species complex, which includes the volant brown and Chatham Island teals as well as the flightless, sub-Antarctic Auckland and Campbell Island teals, radiated within the past 0.9 - 2.2 million years. The divergence of the extinct Chatham Island teal, and the stepping-stone colonisation of the Auckland and Campbell Islands occurred from mainland New Zealand. Morphological changes towards flightlessness are also present in the volant brown teal on mainland New Zealand, suggesting that this group was on the pathway to flightlessess, which accelerated in some insular island lineages.
Acquisition of auditory discrimination mediated by different processes through two distinct circuits linked to the lateral striatum
Authors: Setogawa Susumu , Okauchi Takashi , Hu Di , Wada Yasuhiro , Hikishima Keigo , Onoe Hirotaka , Nishizawa Kayo , Sakayori Nobuyuki , Miyawaki Hiroyuki , Kitanishi Takuma , Mizuseki Kenji , Cui Yilong , Kobayashi Kazuto
Published: October 2023

The striatum, the central hub of cortico-basal ganglia loops, contains functionally heterogeneous subregions distinguished by the topographic patterns of structural connectivity. These subregions mediate various processes of procedural learning. However, it remains unclear when and how striatal subregions engage in the acquisition of sensory stimulus-based decision-making. A neuroimaging of regional brain activity shows that the anterior dorsolateral striatum (aDLS) and posterior ventrolateral striatum (pVLS) in rats are activated in a different temporal pattern during the acquisition phase of auditory discrimination. Chronic and transient pharmacologic manipulations show that the aDLS promotes the behavioral strategy driven by the stimulus-response association while suppressing that by the response-outcome association, and that the pVLS contributes to forming and maintaining the stimulus-response strategy. Electrophysiological recording indicates that subpopulations of aDLS neurons predominantly represent the outcome of specific behaviors at the initial period of discrimination learning, and that pVLS subpopulations encode the beginning and ending of each behavior according to the progress of learning. In addition, other subpopulations of striatal neurons indicate sustained activation after obtaining reward with distinct patterns reflecting the stimulus-response associations. Our findings demonstrate that aDLS and pVLS neurons integrate the new learning of auditory discrimination in spatiotemporally and functionally different manners.
Virological characteristics of the SARS-CoV-2 Omicron EG.5.1 variant
Authors: Tsujino Shuhei , Deguchi Sayaka , Nomai Tomo , Padilla-Blanco Miguel , Plianchaisuk Arnon , Wang Lei , Begum MST Monira , Uriu Keiya , Mizuma Keita , Nao Naganori , Kojima Isshu , Tsubo Tomoya , Li Jingshu , Matsumura Yasufumi , Nagao Miki , Oda Yoshitaka , Tsuda Masumi , Anraku Yuki , Kita Shunsuke , Yajima Hisano , Sasaki-Tabata Kaori , Guo Ziyi , Hinay Alfredo A , Yoshimatsu Kumiko , Yamamoto Yuki , Nagamoto Tetsuharu , Asakura Hiroyuki , Nagashima Mami , Sadamasu Kenji , Yoshimura Kazuhisa , Nasser Hesham , Jonathan Michael , Putri Olivia , Kim Yoonjin , Chen Luo , Suzuki Rigel , Tamura Tomokazu , Maenaka Katsumi ,   The Genotype to Phenotype Japan (G2P-Japan) Consortium, Irie Takashi , Matsuno Keita , Tanaka Shinya , Ito Jumpei , Ikeda Terumasa , Takayama Kazuo , Zahradnik Jiri , Hashiguchi Takao , Fukuhara Takasuke , Sato Kei
Published: October 2023

In middle-late 2023, a sublineage of SARS-CoV-2 Omicron XBB, EG.5.1 (a progeny of XBB.1.9.2), is spreading rapidly around the world. Here, we performed multiscale investigations to reveal virological features of newly emerging EG.5.1 variant. Our phylogenetic-epidemic dynamics modeling suggested that two hallmark substitutions of EG.5.1, S:F456L and ORF9b:I5T, are critical to the increased viral fitness. Experimental investigations addressing the growth kinetics, sensitivity to clinically available antivirals, fusogenicity and pathogenicity of EG.5.1 suggested that the virological features of EG.5.1 is comparable to that of XBB.1.5. However, the cryo-electron microscopy reveals the structural difference between the spike proteins of EG.5.1 and XBB.1.5. We further assessed the impact of ORF9b:I5T on viral features, but it was almost negligible at least in our experimental setup. Our multiscale investigations provide the knowledge for understanding of the evolution trait of newly emerging pathogenic viruses in the human population.