bluuebunny/crossref_metadata_2025 huggingface dataset:
Frequencies of 4 tumor-infiltrating lymphocytes potently predict survival in glioblastoma, an immune desert
Authors: Gershon Rotem , Polevikov Antonina , Karepov Yevgeny , Shenkar Anatoly , Ben-Horin Idan , Alter Regev Tal , Dror-Levinsky Meytal , Lipczyc Kelly , Gasri-Plotnitsky Lital , Diamant Gil , Shapira Nati , Bensimhon Barak , Hagai Aharon , Shahar Tal , Grossman Rachel , Ram Zvi , Volovitz Ilan
Published: October 2023

Background

GBM is an aggressive grade 4 primary brain tumor (BT), with a 5%–13% 5-year survival. Most human GBMs manifest as immunologically “cold” tumors or “immune deserts,” yet the promoting or suppressive roles of specific lymphocytes within the GBM tumor microenvironment (TME) is of considerable debate.

Methods

We used meticulous multiparametric flow cytometry (FC) to determine the lymphocytic frequencies in 102 GBMs, lower-grade gliomas, brain metastases, and nontumorous brain specimen. FC-attained frequencies were compared with frequencies estimated by “digital cytometry.” The FC-derived data were combined with the patients’ demographic, clinical, molecular, histopathological, radiological, and survival data.

Results

Comparison of FC-derived data to CIBERSORT-estimated data revealed the poor capacity of digital cytometry to estimate cell frequencies below 0.2%, the frequency range of most immune cells in BTs. Isocitrate dehydrogenase (IDH) mutation status was found to affect TME composition more than the gliomas’ pathological grade. Combining FC and survival data disclosed that unlike other cancer types, the frequency of helper T cells (Th) and cytotoxic T lymphocytes (CTL) correlated negatively with glioma survival. In contrast, the frequencies of γδ-T cells and CD56bright natural killer cells correlated positively with survival. A composite parameter combining the frequencies of these 4 tumoral lymphocytes separated the survival curves of GBM patients with a median difference of 10 months (FC-derived data; P < .0001, discovery cohort), or 4.1 months (CIBERSORT-estimated data; P = .01, validation cohort).

Conclusions

The frequencies of 4 TME lymphocytes strongly correlate with the survival of patients with GBM, a tumor considered an immune desert.
Acute kidney injury after cardiac surgery
Authors: von Groote Thilo , Sadjadi Mahan , Zarbock Alexander
Published: October 2023

Purpose of review

Patients undergoing cardiac surgery are at high risk to develop cardiac surgery-associated acute kidney injury (CS-AKI) postoperatively. CS-AKI is associated with an increased risk for persistent renal dysfunction, morbidity and mortality. This review summarizes the epidemiology and pathophysiology of CS-AKI, as well as current treatment and prevention strategies.

Recent findings

As AKI is a syndrome with complex pathophysiology, no causative treatment strategies exist. Recent advances in the field of AKI biomarkers offer new perspectives on the issue and the implementation of biomarker-guided preventive strategies may reduce rates of CS-AKI. Finally, nephroprotective treatments and angiotensin II as a novel vasopressor may offer new opportunities for high-risk patients undergoing cardiac surgery.

Based on the described novel approaches for early detection, prevention and management of CS-AKI, a precision-medicine approach should be implemented in order to prevent the development of AKI in patients undergoing cardiac surgery.
The high-risk pediatric patient for ambulatory surgery
Authors: Webber Audra M. , Brennan Marjorie
Published: October 2023

Purpose of review

The aim of this article is to briefly review the pediatric ambulatory surgery landscape, identify two of the most common comorbidities affecting this population, examine the influence of pediatric obesity and sleep disordered breathing (SDB)/obstructive sleep apnea (OSA) on perioperative care, and provide information that can be used when formulating site specific criteria for ambulatory surgical centers.

Recent findings

Most pediatric surgeries performed are now ambulatory, a majority of which take place outside of academic centers. Children with comorbidities such as obesity and SDB/OSA are undergoing surgical or diagnostic procedures which were previously deemed unacceptable for ambulatory surgery. The increase in pediatric ambulatory surgery coupled with a recent shortage of pediatric anesthesiologists means many children will receive anesthesia care from general clinicians who care for children intermittently and may be unfamiliar with the perioperative risks these comorbidities can present.

Our pediatric ambulatory surgical population is anticipated to demonstrate increasing rates of obesity and SDB/OSA. Bringing attention to potential perioperative complications associated with these comorbidities provides a stronger foundation upon which to formulate criteria for individual ambulatory centers. It allows for targeted anesthetic management, influences provider assignments and/or staffing ratios, and informs scheduling times. For anesthesiologists who do not practice pediatric anesthesia daily, knowing what to anticipate plays a significant role in the ability to eliminate surprises and care for these patients safely.
Nutrition support for patients on mechanical circulatory support
Authors: Dresen Ellen , Modir Ranna , Stoppe Christian
Published: October 2023

Purpose of review

No specific guidelines on medical nutrition therapy (MNT) in patients on different types of mechanical circulatory support (MCS) devices yet exist and overall evidence is limited. The purpose of this narrative review is to provide an overview about current existing evidence, which might be of underrecognized importance for the patients‘ short-term and long-term clinical and functional outcomes.

Recent findings

Patients on MCS inherit substantial metabolic, endocrinologic, inflammatory, and immunologic alterations, and together with the specificities of MCS therapy, technical modalities of respective devices, and concomitant medication, the consideration of individualized MNT approaches is indicated in routine clinical practice. Exemplarily, the evaluation of the patients’ individual nutrition status, determination of nutrition targets, progressive increase of energy and protein supply throughou

t the different phases of disease, prevention of micronutrient deficiencies, implementation of nutrition protocols, appropriate monitoring strategies, and continuous quality improvement are essential elements of MNT in patient on MCS.

The importance of MNT for patients on MCS still often remains underrecognized, which might be of particular relevance in view of the significant metabolic alterations, the long treatment period, and severity of illness in these patients. Further research on more targeted MNT approaches in those patients is urgently needed for the generation of evidence-based guidelines for this specific cohort of critically ill patients.
Potential subtype-specific therapeutic approaches in small cell lung cancer
Authors: Horvath Lilla , Lang Christian , Boettiger Kristiina , Aigner Clemens , Dome Balazs , Megyesfalvi Zsolt
Published: October 2023

Purpose of review

Small cell lung cancer (SCLC) remains one of the most aggressive thoracic malignancies with an especially dismal prognosis. While the detection of various targetable driver mutations and immune checkpoints have revolutionized the treatment of non-small cell lung cancer (NSCLC), there has been only modest therapeutic innovation over the past decades in SCLC. In this review, we aim to provide a brief summary on the clinical relevance of recent research findings, which could soon pave the way towards a more personalized and targeted management of SCLC patients.

Recent findings

Substantial research on the biological and molecular heterogeneity of SCLC has been conducted in the last years. Recent results from comprehensive profiling studies have shown that unique major SCLC subtypes can be distinguished based on the relative expression of key transcription regulators (ASCL1, NEUROD1, POU2F3) or distinct inflammatory features. Understanding the differing molecular characteristics of these distinct subtypes has resulted in the identification of specific therapeutic vulnerabilities.

The recently introduced molecular SCLC subtype classification represents a substantial progress towards a personalized and more efficacious approach in SCLC. The consequences of this paradigm shift provide hope for improved patient care and clinical outcomes in this exceptionally lethal thoracic malignancy.
Extracorporeal cardiopulmonary resuscitation in out-of-hospital cardiac arrest – current status
Authors: Suverein Martje M. , Maessen Jos G. , van de Poll Marcel C.G.
Published: October 2023

Purpose of review

Extracorporeal cardiopulmonary resuscitation (ECPR) is an emerging treatment for refractory cardiac arrest. In recent years, several randomized controlled trials have been published that aimed to address the efficacy and effectiveness of ECPR for out-of-hospital cardiac arrest (OHCA). Despite the lack of high-quality evidence concerning clinical effectiveness and cost-effectiveness, ECPR is increasingly implemented throughout the world. In this review, we aim to provide an overview of the current status of ECPR for OHCA.

Recent findings

Randomized controlled trials showed diverging results, largely due to differences in selection criteria and study design. Single-center studies, performed in centers with extraordinary expertise and dedication consistently achieve a low-flow time of around 60 min, but such achievements are rarely reproduced outside these centers. Strict patient selection can improve outcome but simultaneously limits the caseload. Preliminary data suggest that outcome may also be improved by avoiding hyperoxia postresuscitation.

The potential of ECPR to increase survival in selected patients in highly dedicated systems seems to be proven, the question remains whether ECPR for OHCA can be widely implemented successfully and can develop into a sustainable, commonplace resource-effective treatment.
To B(enign) or Not to B: functionalisation of variant in a mild form of argininosuccinate lyase deficiency identified through newborn screening
Authors: Heng Thurston Yan Jia , Ow Jin Rong , Koh Ai Ling , Lim James Soon Chuan , Ong Christine Bee Keow , Goh Jasmine Chew Yin , Lim Jiin Ying , Chiou Fang Kuan , Jamuar Saumya Shekhar
Published: October 2023

Argininosuccinate lyase (ASL) deficiency is an autosomal recessive disorder of the urea cycle with a diverse spectrum of clinical presentation that is detectable in newborn screening. We report an 8-year-old girl with ASL deficiency who was detected through newborn screening and was confirmed using biochemical and functional assay. She is compound heterozygous for a likely pathogenic variant NM_000048.4(ASL):c.283C>T (p.Arg95Cys) and a likely benign variant NM_000048.4(ASL): c.1319T>C (p.Leu440Pro). Functional characterisation of the likely benign genetic variant in ASL was performed. Genomic sequencing was performed on the index patient presenting with non-specific symptoms of poor feeding and lethargy and shown to have increased serum and urine argininosuccinic acid. Functional assay using HEK293T cell model was performed. ASL enzymatic activity was reduced for Leu440Pro. This study highlights the role of functional testing of a variant that may appear benign in a patient with a phenotype consistent with ASL deficiency, and reclassifies NM_000048.4(ASL): c.1319T>C (p.Leu440Pro) variant as likely pathogenic.
Diet and migraine: what is proven?
Authors: Gazerani Parisa
Published: October 2023

Purpose of review

The purpose of this review is to present the latest research findings about diet and migraine, what can be used in the clinic now, and what needs further investigation.

Recent findings

Recent findings highlight that dietary triggers exist for migraine, for example, coffee and alcohol, according to a new systematic review. Elimination diets must be personalized to delineate a balanced diet with acceptable quality and pattern. A piece of average-quality evidence shows that the ketogenic diet (KD) and the Dietary Approaches to Stop Hypertension (DASH) are effective in reducing the frequency, duration, and severity of migraine headaches in adult patients. The gut microbiome is altered in patients with migraine, and further research will identify the benefits of pre and probiotic use for migraine. Advanced digital technology in continuous monitoring can provide educational content based on patients’ needs, help patients adhere to dietary plans, and strengthen personalized care. The complex interaction of lifestyle factors, the influence of age and sex, and patients’ needs in various life phases are essential in formulating dietary plans.

The diet-migraine interaction is a dynamic bidirectional phenomenon that requires careful monitoring, review, and justification of dietary choices to yield the optimal outcome while minimizing potential risks.
Assessing the efficacy of duration and intensity prescription for physical activity in mitigating cardiometabolic risk after spinal cord injury
Authors: Farkas Gary J. , Caldera Lizeth J. , Nash Mark S.
Published: October 2023

Purpose of review

Spinal cord injury (SCI) heightens susceptibility to cardiometabolic risk (CMR), predisposing individuals to cardiovascular disease. This monograph aims to assess the optimal duration and intensity of physical activity (PA) for managing CMR factors, particularly obesity, after SCI and provide modality-specific PA durations for optimal energy expenditure.

Recent findings

PA guidelines recommend at least 150 min/week of moderate-intensity activity. However, non-SCI literature supports the effectiveness of engaging in vigorous-intensity PA (≥6 METs) and dedicating 250–300 min/week (≈2000 kcal/week) to reduce CMR factors. Engaging in this volume of PA has shown a dose-response relationship, wherein increased activity results in decreased obesity and other CMR factors in persons without SCI.

To optimize cardiometabolic health, individuals with SCI require a longer duration and higher intensity of PA to achieve energy expenditures comparable to individuals without SCI. Therefore, individuals with SCI who can engage in or approach vigorous-intensity PA should prioritize doing so for at least 150 min/wk. At the same time, those unable to reach such intensities should engage in at least 250–300 min/week of PA at a challenging yet comfortable intensity, aiming to achieve an optimal intensity level based on their abilities. Given the potential to decrease CMR after SCI, increasing PA duration and intensity merits careful consideration in future SCI PA directives.
Novel trial designs in neuro-oncology
Authors: Song Kun-Wei , Wen Patrick Y.
Published: October 2023

Purpose of review

An important factor contributing to the low rate of success in identifying effective therapies for brain tumor patients is the slow, inefficient, and expensive process of drug development, as well as small patient numbers, low patient participation in clinical trials, and reluctance of patients to enroll in ineffective control arms. In recent years, a number of novel trial designs have been developed to try to address some of these issues.

Recent findings

Surgical ‘window-of-opportunity’ trials that evaluate tumor drug concentrations and pharmacodynamic effects provide invaluable early data early guiding the development of novel therapies. Basket and bucket trials facilitate the development of therapies that target specific biomarkers subsets. Platform trials utilizing Bayesian adaptive randomization and shared control arms such as the INSIGhT and GBM-AGILE trials increase the efficiency and cost-effectiveness of developing novel therapies. There is also growing interest in leveraging external control arms with patient level data to evaluate efficacy in single arm trials, and facilitate interim analysis and potentially reduce the number of control patients in randomized trials.

These novel designs will hopefully reduce the inefficiencies of developing novel therapies in neuro-oncology and facilitate the identification of more effective therapies for brain tumor patients.
How to evaluate extent of resection in diffuse gliomas: from standards to new methods
Authors: Teske Nico , Tonn Joerg-Christian , Karschnia Philipp
Published: October 2023

Purpose of review

Maximal safe tumor resection represents the current standard of care for patients with newly diagnosed diffuse gliomas. Recent efforts have highlighted the prognostic value of extent of resection measured as residual tumor volume in patients with isocitrate dehydrogenase (IDH)-wildtype and -mutant gliomas. Accurate assessment of such information therefore appears essential in the context of clinical trials as well as patient management.

Recent findings

Current recommendations for evaluation of extent of resection rest upon standardized postoperative MRI including contrast-enhanced T1-weighted sequences, T2-weighted/fluid-attenuated-inversion-recovery sequences, and diffusion-weighted imaging to differentiate postoperative tumor volumes from ischemia and nonspecific imaging findings. In this context, correct timing of postoperative imaging within the postoperative period is of utmost importance. Advanced MRI techniques including perfusion-weighted MRI and MR-spectroscopy may add further insight when evaluating residual tumor remnants. Positron emission tomography (PET) using amino acid tracers proves beneficial in identifying metabolically active tumor beyond anatomical findings on conventional MRI.

Future efforts will have to refine recommendations on postoperative assessment of residual tumor burden in respect to differences between IDH-wildtype and -mutant gliomas, and incorporate the emerging role of advanced imaging modalities like amino acid PET.
Remote Ischemic conditioning as an emerging tool to improve corticospinal transmission in individuals with chronic spinal cord injury
Authors: Wu Yu-Kuang , Wecht Jill M. , Bloom Ona E. , Panza Gino S. , Harel Noam Y.
Published: October 2023

Purpose of review

Remote ischemic conditioning (RIC) involves transient blood flow restriction to one limb leading to systemic tissue-protective effects. RIC shares some potential underlying mechanisms with intermittent hypoxia (IH), in which brief bouts of systemic hypoxia trigger increases in growth factor expression and neural plasticity. RIC has shown promise in acute myocardial infarction and stroke but may be applicable toward chronic neuropathology as well. Consequently, this review discusses similarities and differences between RIC and IH and presents preliminary and ongoing research findings regarding RIC.

Recent findings

Several publications demonstrated that combining RIC with motor training may enhance motor learning in adults with intact nervous systems, though the precise mechanisms were unclear. Our own preliminary data has found that RIC, in conjunction with task specific exercise, can increase corticospinal excitability in a subset of people without neurological injury and in those with chronic cervical spinal cord injury or amyotrophic lateral sclerosis.

RIC is a low-cost intervention easy to deliver in a clinical or home setting. Its potential application to facilitate neural plasticity and motor learning during rehabilitation training for individuals with chronic neurological disorders is a novel concept requiring further investigation to characterize mechanisms, safety, and efficacy.
Novel approaches to treatment of leptomeningeal metastases
Authors: Primdahl Ditte , Cohen-Nowak Adam , Kumthekar Priya
Published: October 2023

Purpose of review

The incidence of leptomeningeal metastases is increasing in the setting of improved survival from systemic cancers. In more recent years, our understanding of leptomeningeal metastasis pathogenesis, how to diagnose and treat has been evolving.

Recent findings

Diagnosing leptomeningeal metastasis has been challenging due to the limitations of cytology and neuroimaging; However, newer techniques detecting circulating tumor cells (CTCs) or circulating tumor DNA (ctDNA) have shown potential advantage with diagnosis, quantification and detection of oncogenic mutations. The use of small molecule inhibitors and immunotherapy has shown some promise in specific leptomeningeal metastasis subtypes.

These new discoveries have improved clinical trials’ ability to assess treatment response and thereby more optimally compare different treatments. Furthermore, they have helped the individual clinician better diagnose, monitor the disease and provide novel therapies.
COVID-19 related headaches: epidemiology, pathophysiology, impacts, and management
Authors: Aiyegbusi Olalekan Lee
Published: October 2023

Purpose of review

This is an expert overview of the recent literature on the nature, epidemiology, pathophysiology, impact, and management of COVID-19 related headache, in the acute phase of infection and in post-COVID-19 syndrome.

Recent findings

Headache is one of the commonest symptoms of COVID-19 during acute infection and it is often experienced by individuals who go on to develop long COVID. There is a higher prevalence of headache in individuals with long COVID who contracted the Delta variant than in those who were infected with the Wuhan or Alpha variants. Headaches related to COVID-19 infection are commoner and may be more intense in women.

There are indications that presence of headache might indicate a more benign COVID-19 infection and a better chance of survival. However, the impact of COVID-19 related headache could be substantial leading to poor quality of life in individuals affected. Headache that changes in its nature in terms of frequency and severity should be investigated to exclude cerebrovascular complications. There are promising new therapies for its treatment, but further research is needed.

The findings of this review can promote a better understanding of COVID-19 related headache and guide clinicians in the management of patients.
Systemic vasculitis and headache
Authors: Younger David S.
Published: October 2023

Purpose of review

Vasculitis refers to heterogeneous clinicopathologic disorders that share the histopathology of inflammation of blood vessels. Unrecognized and therefore untreated, vasculitis of the nervous system or so called neurovasculitides, lead to pervasive injury and disability making these disorder of paramount importance to clinicians.

Recent findings

Headache is an important clue to vasculitic involvement of central nervous system (CNS) vessels. CNS vasculitis may be primary, in which only intracranial vessels are involved in the inflammatory process, or secondary to another known disorder with overlapping systemic involvement. A suspicion of vasculitis based on the history, clinical examination, or laboratory studies warrants prompt evaluation and treatment to forestall progression and avert cerebral ischemia or infarction. There has been remarkable progress in the pathogenesis, diagnosis, and treatment of primary adult and pediatric CNS vasculitides predicated on achievements in primary systemic forms.

Vasculitis can be diagnosed with certainty after intensive evaluation that includes tissue confirmation whenever possible. Clinicians must choose from among the available immune modulating, suppressive, and targeted immunotherapies to induce and maintain remission status and prevent relapse, tempered by the recognition of anticipated medication side effects.
Epidemiology and genetics of Meniere's disease
Authors: Lopez-Escamez Jose A. , Liu Ying
Published: October 2023

Purpose of review

This review discusses the recent developments on the understanding of epidemiology and genetics of Meniere's disease.

Recent findings

Meniere's disease has been shown to be associated with several comorbidities, such as migraine, anxiety, allergy and immune disorders. Recent studies have investigated the relationship between environmental factors and Meniere's disease such as air pollution, allergy, asthma, osteoporosis or atmospheric pressure, reporting specific comorbidities in East Asian population. The application of exome sequencing has enabled the identification of genes sharing rare missense variants in multiple families with Meniere's disease, including OTOG and TECTA and suggesting digenic inheritance in MYO7A. Moreover, knockdown of DTNA gene orthologue in Drosophila resulted in defective proprioception and auditory function. DTNA and FAM136A knockout mice have been studied as potential mouse models for Meniere's disease.

While it has attracted emerging attention in recent years, the study of Meniere's disease genetics is still at its early stage. More geographically and ethnically based human genome studies, and the development of cellular and animal models of Meniere's disease may help shed light on the molecular mechanisms of Meniere's disease and provide the potential for gene-specific therapies.
New trends in personalized treatment of depression
Authors: Sampogna Gaia , Toni Claudia , Catapano Pierluigi , Rocca Bianca Della , Di Vincenzo Matteo , Luciano Mario , Fiorillo Andrea
Published: October 2023

Purpose of review

Major depressive disorder (MDD) is a common and burdensome severe mental disorder, which is expected to become the leading cause of disease burden worldwide. Most patients with MDD remain untreated/undertreated. For many decades “a trial and error” approach has been adopted for selecting the best treatment plan for each individual patient, but more recently a personalized treatment approach has been proposed, by taking into account several individual and clinical factors (e.g., clinical stage, comorbidity, duration of illness). Therefore, the aim of this study is to address the most relevant innovations in the personalized treatment plan for patients with MDD.

Recent findings

In recent years, several pharmacological and nonpharmacological innovations have been introduced in the treatment of patients with MDD. As regards pharmacological treatments, the newly developed drugs have an innovative mechanism of action, targeting the glutamatergic systems. These drugs are highly effective in improving depressive symptoms, with a good level of safety and tolerability. As regards nonpharmacological interventions, innovations include both new strategies targeting different domains (e.g., lifestyle interventions aiming to improve the physical symptoms of depression or virtual reality) and classical interventions provided through innovative mechanisms (e.g., web-based psychotherapies and use of digital approaches). Patients globally report a good level of acceptability of these interventions.

Depression is a heterogeneous, complex and multidimensional disorder, representing one of the leading causes of disability worldwide. The final aim of the management of patients is functional recovery, which can be achieved by using personalized, integrated and recovery-oriented interventions. Several innovative pharmacological and nonpharmacological treatments are now available; interventions should be selected on the basis of the patient's needs and preferences in order to tailor the treatment, according to a shared decision-making approach.
Buoyancy forcing and the subpolar Atlantic meridional overturning circulation
Authors: Buckley Martha W. , Lozier M. Susan , Desbruyères Damien , Evans Dafydd Gwyn
Published: October 2023

The North Atlantic meridional overturning circulation and its variability are examined in terms of the overturning in density space and diapycnal water mass transformation. The magnitude of the mean overturning is similar to the surface water mass transformation, but the density and properties of these waters are modified by diapycnal mixing. Surface waters are progressively densified while circulating cyclonically around the subpolar gyre, with the densest waters and deepest convection occurring in the Labrador Sea and Nordic Seas. The eddy-driven interaction between the convective interior and boundary currents is a key to the export of dense waters from marginal seas. Due to the multitude of pathways of dense waters within the subpolar gyre, as well as mixing with older waters, waters exiting the subpolar gyre have a wide range of ages, with a mean age on the order of a decade. As a result, interannual changes in water mass transformation are mostly balanced locally and do not result in changes in export to the subtropics. Only persistent changes in water mass transformation result in changes in export to the subtropics. The dilution of signals from upstream water mass transformation suggests that variability in export of dense waters to the subtropics may be controlled by other processes, including interaction of dense waters with the energetic upper ocean.

This article is part of a discussion meeting issue ‘Atlantic overturning: new observations and challenges’.
Observed mechanisms activating the recent subpolar North Atlantic Warming since 2016
Authors: Chafik Léon , Penny Holliday N. , Bacon Sheldon , Baker Jonathan A. , Desbruyères Damien , Frajka-Williams Eleanor , Jackson Laura C.
Published: October 2023

The overturning circulation of the subpolar North Atlantic (SPNA) plays a fundamental role in Earth’s climate variability and change. Here, we show from observations that the recent warming period since about 2016 in the eastern SPNA involves increased western boundary density at the intergyre boundary, likely due to enhanced buoyancy forcing as a response to the strong increase in the North Atlantic Oscillation since the early 2010s. As these deep positive density anomalies spread southward along the western boundary, they enhance the North Atlantic Current and associated meridional heat transport at the intergyre region, leading to increased influx of subtropical heat into the eastern SPNA. Based on the timing of this chain of events, we conclude that this recent warming phase since about 2016 is primarily associated with this observed mechanism of changes in deep western boundary density, an essential element in these interactions.

This article is part of a discussion meeting issue ‘Atlantic overturning: new observations and challenges’.
Arctic freshwater impact on the Atlantic Meridional Overturning Circulation: status and prospects
Authors: Haine Thomas W. N. , Siddiqui Ali H. , Jiang Wenrui
Published: October 2023

Arguably, the most conspicuous evidence for anthropogenic climate change lies in the Arctic Ocean. For example, the summer-time Arctic sea ice extent has declined over the last 40 years and the Arctic Ocean freshwater storage has increased over the last 30 years. Coupled climate models project that this extra freshwater will pass Greenland to enter the sub-polar North Atlantic Ocean (SPNA) in the coming decades. Coupled climate models also project that the Atlantic Meridional Overturning Circulation (AMOC) will weaken in the twenty-first century, associated with SPNA buoyancy increases. Yet, it remains unclear when the Arctic anthropogenic freshening signal will be detected in the SPNA, or what form the signal will take. Therefore, this article reviews and synthesizes the state of knowledge on Arctic Ocean and SPNA salinity variations and their causes. This article focuses on the export processes in data-constrained ocean circulation model hindcasts. One challenge is to quantify and understand the relative importance of different competing processes. This article also discusses the prospects to detect the emergence of Arctic anthropogenic freshening and the likely impacts on the AMOC. For this issue, the challenge is to distinguish anthropogenic signals from natural variability.

This article is part of a discussion meeting issue ‘Atlantic overturning: new observations and challenges’.
Challenges simulating the AMOC in climate models
Authors: Jackson Laura C. , Hewitt Helene T. , Bruciaferri Diego , Calvert Daley , Graham Tim , Guiavarc’h Catherine , Menary Matthew B. , New Adrian L. , Roberts Malcolm , Storkey David
Published: October 2023

The latest assessment report from the Intergovernmental Panel on Climate Change concluded that the Atlantic Meridional Overturning Circulation (AMOC) was very likely to decline over the twenty-first century under all emissions scenarios; however, there was low confidence in the magnitude of the decline. Recent research has highlighted that model biases in the mean climate state can affect the AMOC in its mean state, variability and its response to climate change. Hence, understanding and reducing these model biases is critical for reducing uncertainty in the future changes of the AMOC and in its impacts on the wider climate. We discuss how model biases, in particular salinity biases, influence the AMOC and deep convection. We then focus on biases in the UK HadGEM3-GC3-1 climate model and how these biases change with resolution. We also discuss ongoing model development activities that affect these biases, and highlight priorities for improved representation of processes, such as the position of the North Atlantic Current, transports in narrow boundary current, resolution (or improved parameterization) of eddies and spurious numerical mixing in overflows.

This article is part of a discussion meeting issue ‘Atlantic overturning: new observations and challenges’.
Towards two decades of Atlantic Ocean mass and heat transports at 26.5° N
Authors: Johns William E. , Elipot Shane , Smeed David A. , Moat Ben , King Brian , Volkov Denis L. , Smith Ryan H.
Published: October 2023

Continuous measurements of the Atlantic meridional overturning circulation (AMOC) and meridional ocean heat transport at 26.5° N began in April 2004 and are currently available through December 2020. Approximately 90% of the total meridional heat transport (MHT) at 26.5° N is carried by the zonally averaged overturning circulation, and an even larger fraction of the heat transport variability (approx. 95%) is explained by the variability of the zonally averaged overturning. A physically based separation of the heat transport into large-scale AMOC, gyre and shallow wind-driven overturning components remains challenging and requires new investigations and approaches. We review the major interannual changes in the AMOC and MHT that have occurred over the nearly two decades of available observations and their documented impacts on North Atlantic heat content. Changes in the flow-weighted temperature of the Florida Current (Gulf Stream) over the past two decades are now taken into account in the estimates of MHT, and have led to an increased heat transport relative to the AMOC strength in recent years. Estimates of the MHT at 26.5° N from coupled models and various surface flux datasets still tend to show low biases relative to the observations, but indirect estimates based on residual methods (top of atmosphere net radiative flux minus atmospheric energy divergence) have shown recent promise in reproducing the heat transport and its interannual variability.

This article is part of a discussion meeting issue ‘Atlantic overturning: new observations and challenges’.
Labrador sea water spreading and the Atlantic meridional overturning circulation
Authors: Le Bras Isabela Alexander-Astiz
Published: October 2023

In 1982, Talley and McCartney used the low potential vorticity signature of Labrador Sea Water (LSW) to make the first North Atlantic maps of its properties. Forty years later, our understanding of LSW variability, spreading time scales and importance has deepened. In this review and synthesis article, I showcase recent observational advances in our understanding of how LSW spreads from its formation regions into the Deep Western Boundary Current and southward into the subtropical North Atlantic. I reconcile the fact that decadal variability in LSW formation is reflected in the Deep Western Boundary Current with the fact that LSW formation does not control subpolar overturning strength and discuss hypothesized connections between LSW spreading and decadal Atlantic Meridional Overturning Circulation variability. Ultimately, LSW spreading is of fundamental interest because it is a significant pathway for dissolved gasses such as oxygen and carbon dioxide into the deep ocean. We should hence prioritize adding dissolved gas measurements to standard hydrographic and circulation observations, particularly at targeted western boundary locations.

This article is part of a discussion meeting issue ‘Atlantic overturning: new observations and challenges’.
Evolution of Atlantic Meridional Overturning Circulation since the last glaciation: model simulations and relevance to present and future
Authors: Liu Zhengyu
Published: October 2023

The Atlantic Meridional Overturning Circulation (AMOC) and the associated water masses have changed dramatically during the glacial–interglacial cycle. Here, I review some recent progress in the modelling of the AMOC and water masses since the Last Glacial Maximum and discuss the relevance of these past AMOC studies to the present and future AMOC study. Recent studies suggested that Atlantic water masses were constrained by carbon isotopes (δ
13
C) and neodymium isotopes (ε
Nd
), while the strength of the AMOC better was constrained by protactinium/thorium ratio (
231
Pa/
230
Th) and the spatial gradient of calcite oxygen isotopes (δ
18
O

c

). In spite of the shallower AMOC at the glacial period, its intensity did not differ substantially from the present because of the cancellation of opposite responses to the rising CO
2
and the retreating ice sheet.

This article is part of a discussion meeting issue ‘Atlantic overturning: new observations and challenges’.
Overturning in the subpolar North Atlantic: a review
Authors: Lozier M. Susan
Published: October 2023

The Overturning in the Subpolar North Atlantic Program (OSNAP) was initiated in the spring of 2010 through a collaborative effort involving the USA, the UK, Germany, the Netherlands and Canada. A key feature of OSNAP is a trans-basin observing system deployed in the summer of 2014 for the continuous measure of volume, heat and freshwater fluxes in the subpolar North Atlantic. This review focuses on advancements made possible by the collective OSNAP observations. Chief among those advancements is the quantification of the dominant role of the eastern subpolar North Atlantic in the production of dense waters that reside in the lower limb of the overturning: the Irminger and Iceland basins contributed approximately three times as much dense water compared with the Labrador Sea over the observational period. Other advancements include elucidation of the relationship between convective activity in the basin interior and boundary current anomalies; the spread of overflow waters in the subpolar region; the seasonality of the meridional volume, heat and freshwater fluxes; and the challenges involved in designing a simpler, less costly observing system. Collectively, OSNAP measurements are laying a framework on which to assess the overturning circulation's vulnerability to continued warming and freshening as climate change continues apace.

This article is part of a discussion meeting issue ‘Atlantic overturning: new observations and challenges’.
From theory to RAPID AMOC observations: a personal voyage of discovery
Authors: Marotzke Jochem
Published: October 2023

I review the history of ideas that have led to the establishment of the RAPID monitoring system for the Atlantic Meridional Overturning Circulation (AMOC) at 26.5° N. This history is closely connected to important events in my personal career. Starting from early and largely unsuccessful attempts at formulating a dynamically consistent force balance for the AMOC, I made theoretical progress by separately predicting the density at the eastern and western boundaries and by invoking exact geostrophic balance throughout, including the western boundary current. A remarkable confluence of individuals and ideas then enabled the establishment of the RAPID array, at its core based on monitoring boundary densities and on geostrophy. The RAPID results, such as the surprisingly large sub-seasonal variability, have encouraged AMOC monitoring approaches at other latitudes. I finish by pointing at two theoretical concepts—first, acknowledging the difference between convective mixing and sinking and, second, considering the advective rather than wave propagation of density perturbations in the deep western boundary current—that, together with continued observations and newly available global coupled simulations at very high resolution, should substantially improve our understanding of the causes of AMOC variability.

This article is part of a discussion meeting issue 'Atlantic overturning: new observations and challenges'.
Can we trust projections of AMOC weakening based on climate models that cannot reproduce the past?
Authors: McCarthy Gerard D. , Caesar Levke
Published: October 2023

The Atlantic Meridional Overturning Circulation (AMOC), a crucial element of the Earth's climate system, is projected to weaken over the course of the twenty-first century which could have far reaching consequences for the occurrence of extreme weather events, regional sea level rise, monsoon regions and the marine ecosystem. The latest IPCC report puts the likelihood of such a weakening as ‘very likely’. As our confidence in future climate projections depends largely on the ability to model the past climate, we take an in-depth look at the difference in the twentieth century evolution of the AMOC based on observational data (including direct observations and various proxy data) and model data from climate model ensembles. We show that both the magnitude of the trend in the AMOC over different time periods and often even the sign of the trend differs between observations and climate model ensemble mean, with the magnitude of the trend difference becoming even greater when looking at the CMIP6 ensemble compared to CMIP5. We discuss possible reasons for this observation-model discrepancy and question what it means to have higher confidence in future projections than historical reproductions.

This article is part of a discussion meeting issue 'Atlantic overturning: new observations and challenges'.
Contrasting internally and externally generated Atlantic Multidecadal Variability and the role for AMOC in CMIP6 historical simulations
Authors: Robson Jon , Sutton Rowan , Menary Matthew B. , Lai Michael W. K.
Published: October 2023

Atlantic multidecadal variability (AMV) has long been thought to be an expression of low-frequency variability in the Atlantic Meridional Overturning Circulation (AMOC). However, alternative hypotheses have been forwarded, including that AMV is primarily externally forced. Here, we review the current state of play by assessing historical simulations made for the sixth coupled model intercomparison project (CMIP6). Overall, the importance of external forcing is sensitive to the type of AMV index used, due to the importance of globally coherent externally forced signals in the models. There are also significant contrasts between the processes that drive internally and externally forced AMV, but these processes can be isolated by exploring the multivariate expression of AMV. Specifically, internal variability in CMIP6 models is consistent with an important role of ocean circulation and AMOC and the externally forced AMV is largely a surface-flux forced mechanism with little role for the ocean. Overall, the internal multivariate fingerprint of AMV is similar to the observed, but the externally forced fingerprint appears inconsistent with observations. Therefore, climate models still suggest a key role for ocean dynamics, and specifically AMOC, in observed AMV. Nevertheless, models remain deficient in a number of areas, and a stronger role for externally forced dynamical changes cannot be ruled out.

This article is part of a discussion meeting issue ‘Atlantic overturning: new observations and challenges’.
Should AMOC observations continue: how and why?
Authors: Frajka-Williams E. , Foukal N. , Danabasoglu G.
Published: October 2023

The Atlantic meridional overturning circulation (AMOC) is a large-scale circulation pattern responsible for northward heat transport in the Atlantic and is associated with climate variations on a wide range of time scales. Observing the time-varying AMOC has fundamentally changed our understanding of the large-scale ocean circulation and its interaction with the climate system, as well as identified shortcomings in numerical simulations. With a wide range of gains already achieved, some now ask whether AMOC observations should continue. A measured approach is required for a future observing system that addresses identified gaps in understanding, accounts for shortcomings in observing methods and maximizes the potential to guide improvements in ocean and climate models. Here, we outline a perspective on future AMOC observing and steps that the community should consider to move forward.

This article is part of a discussion meeting issue ‘Atlantic overturning: new observations and challenges’.
FHIR-GPT Enhances Health Interoperability with Large Language Models
Authors: Li Yikuan , Wang Hanyin , Yerebakan Halid Z. , Shinagawa Yoshihisa , Luo Yuan
Published: October 2023

Advancing health interoperability can significantly benefit health research, including phenotyping, clinical trial support, and public health surveillance. Federal agencies, including ONC, CDC, and CMS, have been collectively collaborating to promote interoperability by adopting Fast Healthcare Interoperability Resources (FHIR). However, the heterogeneous structures and formats of health data present challenges when transforming Electronic Health Record (EHR) data into FHIR resources. This challenge becomes more significant when critical health information is embedded in unstructured data rather than well-organized structured formats. Previous studies relied on multiple separate rule-based or deep learning-based NLP tools to complete the FHIR resource transformation, which demands substantial development costs, extensive training data, and meticulous integration of multiple individual NLP tools. In this study, we assessed the ability of large language models (LLMs) to transform clinical narratives into HL7 FHIR resources. We developed FHIR-GPT specifically for the transformation of clinical texts into FHIR medication statement resources. In our experiments using 3,671 snippets of clinical texts, FHIR-GPT demonstrated an exceptional exact match rate of over 90%, surpassing the performance of existing methods. FHIR-GPT improved the exact match rates of existing NLP pipelines by 3% for routes, 12% for dose quantities, 35% for reasons, 42% for forms, and over 50% for timing schedules. Our findings provide the foundations for leveraging LLMs to enhance health data interoperability. Future studies will aim to build upon these successes by extending the generation to additional FHIR resources.