bluuebunny/crossref_metadata_2025 huggingface dataset:
ICARUS v3, a massively scalable web server for single-cell RNA-seq analysis of millions of cells
Authors: Jiang Andrew , Snell Russell G , Lehnert Klaus
Published: March 2024

Motivation

In recent years, improvements in throughput of single-cell RNA-seq have resulted in a significant increase in the number of cells profiled. The generation of single-cell RNA-seq datasets comprising >1 million cells is becoming increasingly common, giving rise to demands for more efficient computational workflows.

Results

We present an update to our single-cell RNA-seq analysis web server application, ICARUS (available at https://launch.icarus-scrnaseq.cloud.edu.au) that allows effective analysis of large-scale single-cell RNA-seq datasets. ICARUS v3 utilizes the geometric cell sketching method to subsample cells from the overall dataset for dimensionality reduction and clustering that can be then projected to the large dataset. We then extend this functionality to select a representative subset of cells for downstream data analysis applications including differential expression analysis, gene co-expression network construction, gene regulatory network construction, trajectory analysis, cell–cell communication inference, and cell cluster associations to GWAS traits. We demonstrate analysis of single-cell RNA-seq datasets using ICARUS v3 of 1.3 million cells completed within the hour.

Availability and implementation

ICARUS is available at https://launch.icarus-scrnaseq.cloud.edu.au.
Sensitive and specific assay for the serological diagnosis of anti-p200 pemphigoid based on the recombinant laminin β4 subunit
Authors: Goletz Stephanie , Probst Christian , Komorowski Lars , Radzimski Christiane , Mindorf Swantje , Holtsche Maike M , Pigors Manuela , van Beek Nina , Zillikens Detlef , Schlumberger Wolfgang , Schmidt Enno
Published: March 2024

Anti-p200 pemphigoid is an autoimmune blistering disease that often resembles other pemphigoid disorders. We developed a test for the detection of autoantibodies against laminin β4, an autoantigen in anti-p200 pemphigoid, to facilitate its diagnosis. The test demonstrated excellent sensitivity and specificity, making it a valuable tool for diagnosing this disease and distinguishing it from similar skin disorders.
Determination of p53abn endometrial cancer: a multitask analysis using radiological-clinical nomogram on MRI
Authors: Ning Yan , Liu Wei , Wang Haijie , Zhang Feiran , Chen Xiaojun , Wang Yida , Wang Tianping , Yang Guang , Zhang He
Published: March 2024

Objectives

We aimed to differentiate endometrial cancer (EC) between TP53mutation (P53abn) and Non-P53abn subtypes using radiological-clinical nomogram on EC body volume MRI.

Methods

We retrospectively recruited 227 patients with pathologically proven EC from our institution. All these patients have undergone molecular pathology diagnosis based on the Cancer Genome Atlas. Clinical characteristics and histological diagnosis were recorded from the hospital information system. Radiomics features were extracted from online Pyradiomics processors. The diagnostic performance across different acquisition protocols was calculated and compared. The radiological-clinical nomogram was established to determine the nonendometrioid, high-risk, and P53abn EC group.

Results

The best MRI sequence for differentiation P53abn from the non-P53abn group was contrast-enhanced T1WI (test AUC: 0.8). The best MRI sequence both for differentiation endometrioid cancer from nonendometrioid cancer and high-risk from low- and intermediate-risk groups was apparent diffusion coefficient map (test AUC: 0.665 and 0.690). For all 3 tasks, the combined model incorporating all the best discriminative features from each sequence yielded the best performance. The combined model achieved an AUC of 0.845 in the testing cohorts for P53abn cancer identification. The MR-based radiomics diagnostic model performed better than the clinical-based model in determining P53abn EC (AUC: 0.834 vs 0.682).

Conclusion

In the present study, the diagnostic model based on the combination of both radiomics and clinical features yielded a higher performance in differentiating nonendometrioid and P53abn cancer from other EC molecular subgroups, which might help design a tailed treatment, especially for patients with high-risk EC.

Advances in knowledge

(1) The contrast-enhanced T1WI was the best MRI sequence for differentiation P53abn from the non-P53abn group (test AUC: 0.8). (2) The radiomics-based diagnostic model performed better than the clinical-based model in determining P53abn EC (AUC: 0.834 vs 0.682). (3) The proposed model derived from multi-parametric MRI images achieved a higher accuracy in P53abn EC identification (AUC: 0.845).
A model that predicts a real-time tumour surface using intra-treatment skin surface and end-of-expiration and end-of-inhalation planning CT images
Authors: Wei Ziwen , Huang Xiang , Sun Aiming , Peng Leilei , Lou Zhixia , Hu Zongtao , Wang Hongzhi , Xing Ligang , Yu Jinming , Qian Junchao
Published: March 2024

Objectives

To develop a mapping model between skin surface motion and internal tumour motion and deformation using end-of-exhalation (EOE) and end-of-inhalation (EOI) 3D CT images for tracking lung tumours during respiration.

Methods

Before treatment, skin and tumour surfaces were segmented and reconstructed from the EOE and the EOI 3D CT images. A non-rigid registration algorithm was used to register the EOE skin and tumour surfaces to the EOI, resulting in a displacement vector field that was then used to construct a mapping model. During treatment, the EOE skin surface was registered to the real-time, yielding a real-time skin surface displacement vector field. Using the mapping model generated, the input of a real-time skin surface can be used to calculate the real-time tumour surface. The proposed method was validated with and without simulated noise on 4D CT images from 15 patients at Léon Bérard Cancer Center and the 4D-lung dataset.

Results

The average centre position error, dice similarity coefficient (DSC), 95%-Hausdorff distance and mean distance to agreement of the tumour surfaces were 1.29 mm, 0.924, 2.76 mm, and 1.13 mm without simulated noise, respectively. With simulated noise, these values were 1.33 mm, 0.920, 2.79 mm, and 1.15 mm, respectively.

Conclusions

A patient-specific model was proposed and validated that was constructed using only EOE and EOI 3D CT images and real-time skin surface images to predict internal tumour motion and deformation during respiratory motion.

Advances in knowledge

The proposed method achieves comparable accuracy to state-of-the-art methods with fewer pre-treatment planning CT images, which holds potential for application in precise image-guided radiation therapy.
SORD-deficient rats develop a motor-predominant peripheral neuropathy unveiling novel pathophysiological insights
Authors: Rebelo Adriana P , Abad Clemer , Dohrn Maike F , Li Jian J , Tieu Ethan K , Medina Jessica , Yanick Christopher , Huang Jingyu , Zotter Brendan , Young Juan I , Saporta Mario , Scherer Steven S , Walz Katherina , Zuchner Stephan
Published: March 2024

Biallelic SORD mutations cause one of the most frequent forms of recessive hereditary neuropathy, estimated to affect ∼10 000 patients in North America and Europe alone. Pathogenic SORD loss-of-function changes in the encoded enzyme sorbitol dehydrogenase result in abnormally high sorbitol levels in cells and serum. How sorbitol accumulation leads to peripheral neuropathy remains to be elucidated.

A reproducible animal model for SORD neuropathy is essential to illuminate the pathogenesis of SORD deficiency and for preclinical studies of potential therapies. Therefore, we have generated a Sord knockout (KO), Sord−/−, Sprague Dawley rat, to model the human disease and to investigate the pathophysiology underlying SORD deficiency.

We have characterized the phenotype in these rats with a battery of behavioural tests as well as biochemical, physiological and comprehensive histological examinations. Sord−/− rats had remarkably increased levels of sorbitol in serum, CSF and peripheral nerve. Moreover, serum from Sord−/− rats contained significantly increased levels of neurofilament light chain, an established biomarker for axonal degeneration. Motor performance significantly declined in Sord−/− animals starting at ∼7 months of age. Gait analysis evaluated with video motion-tracking confirmed abnormal gait patterns in the hindlimbs. Motor nerve conduction velocities of the tibial nerves were slowed. Light and electron microscopy of the peripheral nervous system revealed degenerating myelinated axons, de- and remyelinated axons, and a likely pathognomonic finding—enlarged ‘ballooned’ myelin sheaths. These findings mainly affected myelinated motor axons; myelinated sensory axons were largely spared.

In summary, Sord−/− rats develop a motor-predominant neuropathy that closely resembles the human phenotype. Our studies revealed novel significant aspects of SORD deficiency, and this model will lead to an improved understanding of the pathophysiology and the therapeutic options for SORD neuropathy.
Navigating through the challenges of bullous pemphigoid and breast cancer in older adults
Authors: Yoo Li Jie Helena , Grechin Cristina , Kearney Nicola , Orr Emily , Ryan Stephanie L , O’Kane Marina
Published: March 2024

This article delves into the profound effects of bullous pemphigoid, highlighting its impact on the physical, emotional and psychological wellbeing of an 80-year-old person. It also explores the treatment challenges in the patient's journey while battling breast cancer simultaneously and highlights the success of dupilumab in treating bullous pemphigoid.
Considerations for use of artificial intelligence in the dermatology residency application process
Authors: Aihie Osaigbokan , Kim Eun Jae , Patil Mihir K , Manik Ritika , Nambudiri Vinod E
Published: March 2024

Artificial intelligence (AI) has gained traction in the field of dermatology, but the role of AI in the dermatology residency application process has been minimally explored. We encourage dermatology residency programmes to proactively set guidelines to applicants and letter writers on the use of AI tools. Furthermore, programmes should consider implementing natural language processing models in reviewing residency applications to promote the principles of diversifying the dermatology workforce.
Revolutionizing Daptomycin Dosing: A Single 7–11-Hour Sample for Pragmatic Application
Authors: Angelini Jacopo , Liu Shuhan , Giuliano Simone , Flammini Sarah , Martini Luca , Tascini Carlo , Baraldo Massimo , Pai Manjunath P
Published: March 2024

Precision daptomycin dosing faces clinical implementation barriers despite known exposure-safety concerns with the use of twice the regulatory-approved doses. We propose achieving a single 7–11-hour post-dose plasma target concentration of 30 mg/L to 43 mg/L to be a practical starting point to facilitate precision daptomycin dosing.
Performances of acute kidney injury biomarkers vary according to sex
Authors: Faguer Stanislas , Piedrafita Alexis , Sanz Ana Belen , Siwy Justyna , Mina Ioanna K , Alves Melinda , Bousquet Paul , Marcheix Bertrand , Casemayou Audrey , Klein Julie , Minville Vincent , Breuil Benjamin , Ortiz Alberto , Schanstra Joost P
Published: March 2024

Background

Before implementing individualized strategies to treat acute kidney injury (AKI), identifying clusters of patients with divergent pathophysiological mechanisms, diagnosis criteria or outcomes is of the utmost importance. Here we studied sex-related molecular mechanisms in cardiac bypass (CBP) surgery patients developing AKI.

Methods

We compared the characteristics of 1170 patients referred for CBP surgery using multivariate logistic regression and propensity score–based analysis. Performances of the candidate urinary biomarkers at <4 h post-surgery, urinary neutrophil gelatinase-associated lipocalin (uNGAL), [IGFBP7]·[TIMP-2] product (NephroCheck) and a recently developed AKI signature of 204 urinary peptides (AKI204) to predict AKI were compared in both sexes.

Results

Incidence (∼25%) and severity of AKI were similar in men and women, even after adjustment for the usual risk factors of AKI, including baseline estimated glomerular filtration rate, age, diabetes mellitus, length of CBP and red blood cell transfusion. However, at the molecular level, performances of uNGAL, NephroCheck and AKI204 to predict AKI strongly diverged between men and women. In the full cohort, as well as in subgroups of men and women, the multimarker AKI204 signature outperformed uNGAL and NephroCheck and predicted the development of AKI significantly better in women than in men. Analysis of AKI204 at the single-peptide level suggested divergences of AKI mechanisms between sexes due to increased kidney inflammation in women (increased abundance of urinary fragments of osteopontin and uromodulin).

Conclusions

In patients referred for CBP surgery, significant clinical and biological differences between men and women as well as sexual dimorphism of AKI biomarker performances were identified. The urinary peptide signature points to sex-related molecular mechanisms underlying AKI.
Smarter in the city? Lizards from urban and semi-natural habitats do not differ in a cognitive task in two syntopic species
Authors: Damas-Moreira Isabel , Szabo Birgit , Drosopoulos Georgios , Stober Carolin , Lisičić Duje , Caspers Barbara A
Published: March 2024

Urbanization occurs at a global scale, imposing dramatic and abrupt environmental changes that lead to biodiversity loss. Yet, some animal species can handle these changes, and thrive in such artificial environments. One possible explanation is that urban individuals are equipped with better cognitive abilities, but most studies have focused on birds and mammals and yielded varied results. Reptiles have received much less attention, despite some lizard species being common city dwellers. The Italian wall lizard, Podarcis siculus, and the common wall lizard, Podarcis muralis, are two successful lizards in anthropogenic habitats that thrive in urban locations. To test for differences in a cognitive skill between urban and semi-natural environments, we investigated inhibitory control through a detour task in syntopic populations of the two species, across 249 lizards that were tested in partially artificial field settings. Sophisticated inhibitory control is considered essential for higher degrees of cognitive flexibility and other higher-level cognitive abilities. In this task, we confronted lizards with a transparent barrier, separating them from a desired shelter area that they could only reach by controlling their impulse to go straight and instead detour the barrier. We found no differences between lizards in urban and semi-natural environments, nor between species, but females overall performed better than males. Moreover, 48% of the lizards in our study did not perform a correct trial in any of the 5 trials, hinting at the difficulty of the task for these species. This study is among the first to address lizard cognition, through their inhibitory control, as a potential explanation for success in cities and highlights one should be careful with assuming that urban animals generally have enhanced cognitive performance, as it might be taxa, task, or condition dependent.
Academic Collaboration in the Early Enlightenment: Daniel Waterland (1683–1740) and his Cambridge Tyros
Authors: Bailey Natasha
Published: March 2024

While early modern collaborative practices have long been associated with the natural sciences, humanistic scholarship has mostly been depicted, ever since Mark Pattison’s classic biography of Isaac Casaubon, as a lonely and even self-destructive affair. This article reconstructs a moment in English intellectual history when textual scholars did collaborate in a semi-professional manner. To this end, it examines the relationship between Daniel Waterland, Master of Magdalene College, Cambridge, and three ambitious young scholars who assumed roles within his enterprise: Edmund Law, Thomas Johnson and John Chapman. By showing how an unofficial research team was assembled over several years and directed to perform separate but related tasks with the stated goal of defending the Church of England, the article highlights the dynamics at work within a collective, subtly top-down model of scholarly interaction. Though a passing reference has been made in the historiography to ‘Waterland & Company’, this article is the first to delve into the nature and scope of this network and its sometimes contradictory objectives.
Effect of epoprostenol-induced thrombocytopaenia on lung transplantation for pulmonary arterial hypertension
Authors: Date Naoki , Nakajima Daisuke , Ikeda Masaki , Nishikawa Shigeto , Tanaka Satona , Yamada Yoshito , Yutaka Yojiro , Hamaji Masatsugu , Menju Toshi , Ohsumi Akihiro , Date Hiroshi
Published: March 2024

OBJECTIVES

Preoperative intravenous epoprostenol therapy can cause thrombocytopaenia, which may increase the risk of perioperative bleeding during lung transplantation. This study aimed to determine whether lung transplantation can be safely performed in patients with epoprostenol-induced thrombocytopaenia.

METHODS

From June 2008 to July 2022, we performed 37 lung transplants in patients with pulmonary arterial hypertension (PAH), including idiopathic PAH (n = 26), congenital heart disease-associated PAH (n = 7), pulmonary veno-occlusive disease (n = 3) and peripheral pulmonary artery stenosis (n = 1) at our institution. Of these, 26 patients received intravenous epoprostenol therapy (EPO group), whereas 11 patients were treated with no epoprostenol (no-EPO group). We retrospectively analysed the preoperative and postoperative platelet counts and post-transplant outcomes in each group.

RESULTS

Preoperative platelet counts were relatively lower in the EPO group than in the no-EPO group (median EPO: 127 000 vs no-EPO: 176 000/μl). However, blood loss during surgery was similar between the 2 groups (EPO: 2473 ml vs no-EPO: 2615 ml). The platelet counts significantly increased over 1 month after surgery, and both groups showed similar platelet counts (EPO: 298 000 vs no-EPO: 284 000/μl). In-hospital mortality (EPO: 3.9% vs no-EPO: 18.2%) and the 3-year survival rate (EPO: 91.4% vs no-EPO: 80.8%) were similar between the 2 groups.

CONCLUSIONS

Patients with PAH treated with intravenous epoprostenol showed relatively lower platelet counts, which improved after lung transplantation with good post-transplant outcomes.
Uniportal video-assisted thoracic surgery: segmentectomy versus lobectomy—early outcomes
Authors: Sachs Erik , Jackson Veronica , Al-Ameri Mamdoh , Sartipy Ulrik
Published: March 2024

OBJECTIVES

To assess the feasibility and safety of uniportal video-assisted thoracoscopic pulmonary segmentectomy compared with lobectomy by studying early postoperative outcomes.

METHODS

We included all patients who underwent uniportal segmentectomy and lobectomy between 2017 and 2022 at Karolinska University Hospital. Early clinical outcomes were compared between the uniportal segmentectomy and lobectomy groups. Differences in baseline characteristics were addressed using inverse probability of treatment weighting.

RESULTS

A total of 833 patients (232 segmentectomy, 601 lobectomy) were included. The number of uniportal operations increased during the study period. Patients in the segmentectomy and lobectomy groups, respectively, had stage I lung cancer in 65% and 43% of the cases; 97% and 94% had no postoperative complications, the median number of lymph node stations sampled was 4 vs 5, and non-radical microscopic resection occurred in 1.7% vs 1.8%. The drains were removed on postoperative day 1 in 75% vs 72% of the patients following segmentectomy and lobectomy, respectively, and 90% vs 89% were discharged directly home.

CONCLUSIONS

Uniportal video-assisted segmentectomy was performed with similar early postoperative clinical results compared with uniportal lobectomy in patients with benign, metastatic or early-stage lung cancer.
Clinical and radiological septic joint analysis of spontaneous sternoclavicular joint infections: achieving the best outcomes—a systems engineering approach
Authors: Pothini Tanushri , Wilmot Charles D , Waters John K , Wait Michael A , Reznik Scott I , Jordan Kirk G , Caire Jacqueline T , Ashworth John M , Cady Leah C , Lysikowski Jerzy R , Yen Christina F , Weinschenk Robert C , Samade Richard , Jessen Michael E , Kusiak Andrew , Kernstine Kemp H
Published: March 2024

OBJECTIVES

Spontaneous sternoclavicular joint infection (SSCJI) is a rare and poorly understood disease process. This study aims to identify factors guiding effective management strategies for SSCJI by using data mining.

METHODS

An Institutional Review Board-approved retrospective review of patients from 2 large hospitals (2010–2022) was conducted. SSCJI is defined as a joint infection without direct trauma or radiation, direct instrumentation or contiguous spread. An interdisciplinary team consisting of thoracic surgeons, radiologists, infectious disease specialists, orthopaedic surgeons, hospital information experts and systems engineers selected relevant variables. Small set data mining algorithms, utilizing systems engineering, were employed to assess the impact of variables on patient outcomes.

RESULTS

A total of 73 variables were chosen and 54 analysed against 11 different outcomes. Forty-seven patients [mean age 51 (22–82); 77% male] met criteria. Among them, 34 underwent early joint surgical resection (<14 days), 5 patients received delayed surgical intervention (>14 days) and 8 had antibiotic-only management. The antibiotic-only group had comparable outcomes. Indicators of poor outcomes were soft tissue fluid >4.5 cm, previous SSCJI, moderate/significant bony fragments, HgbA1c >13.9% and moderate/significant bony sclerosis.

CONCLUSIONS

This study suggests that targeted antibiotic-only therapy should be considered initially for SSCJI cases while concurrently managing comorbidities. Patients displaying indicators of poor outcomes or no symptomatic improvement after antibiotic-only therapy should be considered for surgical joint resection.
International consensus on mitotane treatment in pediatric patients with adrenal cortical tumors: indications, therapy, and management of adverse effects
Authors: Riedmeier Maria , Antonini Sonir R R , Brandalise Silvia , Costa Tatiana El Jaick B , Daiggi Camila M , de Figueiredo Bonald C , de Krijger Ronald R , De Sá Rodrigues Karla Emília , Deal Cheri , Del Rivero Jaydira , Engstler Gernot , Fassnacht Martin , Fernandes Luiz Canali Gabriela C , Molina Carlos A Fernandes , Gonc Elmas Nazli , Gültekin Melis , Haak Harm R , Guran Tulay , Hendriks Allaird Emile J , Idkowiak Jan , Kuhlen Michaela , Malkin David , Meena Jagdish Prasad , Pamporaki Christina , Pinto Emilia , Puglisi Soraya , Ribeiro Raul C , Thompson Lester D R , Yalcin Bilgehan , Van Noesel Max , Wiegering Verena
Published: March 2024

Objective

Mitotane is an important cornerstone in the treatment of pediatric adrenal cortical tumors (pACC), but experience with the drug in the pediatric age group is still limited and current practice is not guided by robust evidence. Therefore, we have compiled international consensus statements from pACC experts on mitotane indications, therapy, and management of adverse effects.

Methods

A Delphi method with 3 rounds of questionnaires within the pACC expert consortium of the international network groups European Network for the Study of Adrenal Tumors pediatric working group (ENSAT-PACT) and International Consortium of pediatric adrenocortical tumors (ICPACT) was used to create 21 final consensus statements.

Results

We divided the statements into 4 groups: environment, indications, therapy, and adverse effects. We reached a clear consensus for mitotane treatment for advanced pACC with stages III and IV and with incomplete resection/tumor spillage. For stage II patients, mitotane is not generally indicated. The timing of initiating mitotane therapy depends on the clinical condition of the patient and the setting of the planned therapy. We recommend a starting dose of 50 mg/kg/d (1500 mg/m²/d) which can be increased up to 4000 mg/m2/d. Blood levels should range between 14 and 20 mg/L. Duration of mitotane treatment depends on the clinical risk profile and tolerability. Mitotane treatment causes adrenal insufficiency in virtually all patients requiring glucocorticoid replacement shortly after beginning. As the spectrum of adverse effects of mitotane is wide-ranging and can be life-threatening, frequent clinical and neurological examinations (every 2-4 weeks), along with evaluation and assessment of laboratory values, are required.

Conclusions

The Delphi method enabled us to propose an expert consensus statement, which may guide clinicians, further adapted by local norms and the individual patient setting. In order to generate evidence, well-constructed studies should be the focus of future efforts.
Severe mental illness: cardiovascular risk assessment and management
Authors: Polcwiartek Christoffer , O’Gallagher Kevin , Friedman Daniel J , Correll Christoph U , Solmi Marco , Jensen Svend Eggert , Nielsen René Ernst
Published: March 2024

Patients with severe mental illness (SMI) including schizophrenia and bipolar disorder die on average 15–20 years earlier than the general population often due to sudden death that, in most cases, is caused by cardiovascular disease. This state-of-the-art review aims to address the complex association between SMI and cardiovascular risk, explore disparities in cardiovascular care pathways, describe how to adequately predict cardiovascular outcomes, and propose targeted interventions to improve cardiovascular health in patients with SMI. These patients have an adverse cardiovascular risk factor profile due to an interplay between biological factors such as chronic inflammation, patient factors such as excessive smoking, and healthcare system factors such as stigma and discrimination. Several disparities in cardiovascular care pathways have been demonstrated in patients with SMI, resulting in a 47% lower likelihood of undergoing invasive coronary procedures and substantially lower rates of prescribed standard secondary prevention medications compared with the general population. Although early cardiovascular risk prediction is important, conventional risk prediction models do not accurately predict long-term cardiovascular outcomes as cardiovascular disease and mortality are only partly driven by traditional risk factors in this patient group. As such, SMI-specific risk prediction models and clinical tools such as the electrocardiogram and echocardiogram are necessary when assessing and managing cardiovascular risk associated with SMI. In conclusion, there is a necessity for differentiated cardiovascular care in patients with SMI. By addressing factors involved in the excess cardiovascular risk, reconsidering risk stratification approaches, and implementing multidisciplinary care models, clinicians can take steps towards improving cardiovascular health and long-term outcomes in patients with SMI.
Artificial intelligence–based assessment of built environment from Google Street View and coronary artery disease prevalence
Authors: Chen Zhuo , Dazard Jean-Eudes , Khalifa Yassin , Motairek Issam , Al-Kindi Sadeer , Rajagopalan Sanjay
Published: March 2024

Background and Aims

Built environment plays an important role in the development of cardiovascular disease. Tools to evaluate the built environment using machine vision and informatic approaches have been limited. This study aimed to investigate the association between machine vision–based built environment and prevalence of cardiometabolic disease in US cities.

Methods

This cross-sectional study used features extracted from Google Street View (GSV) images to measure the built environment and link them with prevalence of coronary heart disease (CHD). Convolutional neural networks, linear mixed-effects models, and activation maps were utilized to predict health outcomes and identify feature associations with CHD at the census tract level. The study obtained 0.53 million GSV images covering 789 census tracts in seven US cities (Cleveland, OH; Fremont, CA; Kansas City, MO; Detroit, MI; Bellevue, WA; Brownsville, TX; and Denver, CO).

Results

Built environment features extracted from GSV using deep learning predicted 63% of the census tract variation in CHD prevalence. The addition of GSV features improved a model that only included census tract-level age, sex, race, income, and education or composite indices of social determinant of health. Activation maps from the features revealed a set of neighbourhood features represented by buildings and roads associated with CHD prevalence.

Conclusions

In this cross-sectional study, the prevalence of CHD was associated with built environment factors derived from GSV through deep learning analysis, independent of census tract demographics. Machine vision–enabled assessment of the built environment could potentially offer a more precise approach to identify at-risk neighbourhoods, thereby providing an efficient avenue to address and reduce cardiovascular health disparities in urban environments.
Cleft closure and other predictors of contemporary outcomes after atrioventricular canal repair in patients with parachute left atrioventricular valve
Authors: McGeoghegan Patrick B , Lu Minmin , Sleeper Lynn A , Emani Sitaram M , Baird Christopher W , Feins Eric N , Gellis Laura A , Friedman Kevin G
Published: March 2024

OBJECTIVES

Parachute left atrioventricular valve (LAVV) complicates atrioventricular septal defect (AVSD) repair. We evaluate outcomes of AVSD patients with parachute LAVV and identify risk factors for adverse outcomes.

METHODS

We evaluated all patients undergoing repair of AVSD with parachute LAVV from 2012 to 2021. The primary outcome was a composite of time-to-death, LAVV reintervention and development of greater than or equal to moderate LAVV dysfunction (greater than or equal to moderate LAVV stenosis and/or LAVV regurgitation). Event-free survival for the composite outcome was estimated using Kaplan–Meier methodology and competing risks analysis. Cox proportional hazards regression was used to identify predictors of the primary outcome.

RESULTS

A total of 36 patients were included with a median age at repair of 4 months (interquartile range 2.3–5.5 months). Over a median follow-up of 2.6 years (interquartile range 1.0–5.6 years), 6 (17%) patients underwent LAVV reintervention. All 6 patients who underwent LAVV reintervention had right-dominant AVSD. Sixteen patients (44%) met the composite outcome, and all did so within 2 years of initial repair. Transitional AVSD (versus complete), prior single-ventricle palliation, leaving the cleft completely open and greater than or equal to moderate preoperative LAVV regurgitation were associated with a higher risk of LAVV reintervention in univariate analysis. In multivariate analysis, leaving the cleft completely open was associated with the composite outcome.

CONCLUSIONS

Repair of AVSD with parachute LAVV remains a challenge with a significant burden of LAVV reintervention and dysfunction in medium-term follow-up. Unbalanced, right-dominant AVSDs are at higher risk for LAVV reintervention. Leaving the cleft completely open might independently predict poor overall outcomes and should be avoided when possible.

Clinical trial registration number

IRB-P00041642
Memory Fusion, Diplomatic Agency, and Armenian Genocide Recognition in the Czech Republic
Authors: Fittante Daniel
Published: March 2024

Scholars often emphasize how right-wing political actors in Europe use memory laws to undermine democratic traditions and revise historical accounts. But a broad range of political actors (with diverse motivations) support memory laws. Synthesizing research in international political sociology and memory politics, this analysis examines the relational and social practices of diplomats from small states and the creative strategies of center-left political insiders in the creation and passage of memory laws. Based on data collected in the Czech Republic, the article investigates how relational and social dynamics, in part, inspired members of parliament (from the Czech Social Democratic Party) to insert Armenian Genocide recognition into memory laws about the Holocaust and Second World War in the Chamber of Deputies (2017) and the Senate (2020) – a strategy I refer to as memory fusion. In developing the framework of memory fusion, however, the findings also explore how Turkish diplomats use a similar strategy to pursue their own goals.
Co-occurring microflora and mucin drive Pseudomonas aeruginosa diversification and pathoadaptation
Authors: Bottery Michael J , Johansen Helle Krogh , Pitchford Jon W , Friman Ville-Petri
Published: March 2024

While several environmental factors contribute to the evolutionary diversification of the pathogenic bacterium Pseudomonas aeruginosa during cystic fibrosis lung infections, relatively little is known about the impact of the surrounding microbiota. By using in vitro experimental evolution, we show that the presence of Stenotrophomonas maltophilia, Staphylococcus aureus, or them both, prevent the evolution of loss of virulence, which repeatedly occurs in the absence of these species due to mutations in regulators of the Pseudomonas Quinolone Signal quorum sensing system, vqsM and pqsR. Moreover, the strength of the effect of co-occurring species is attenuated through changes in the physical environment by the addition of mucin, resulting in selection for phenotypes resembling those evolved in the absence of the co-occurring species. Together, our findings show that variation in mucosal environment and the surrounding polymicrobial environment can determine the evolutionary trajectory of P. aeruginosa, partly explaining its diversification and pathoadaptation from acute to chronic phenotype during cystic fibrosis lung infections.
Multiomics plasma effects of switching from triple antiretroviral regimens to dolutegravir plus lamivudine
Authors: de Lazzari Elisa , Negredo Eugenia B , Domingo Pere , Tiraboschi Juan M , Ribera Esteve , Abdulghani Nadia , Alba Verònica , Fernández-Arroyo Salvador , Viladés Consuelo , Peraire Joaquim , Gatell Jose M , Blanco Jose L , Vidal Francesc , Rull Anna , Martinez Esteban
Published: March 2024

Introduction

The DOLAM trial revealed that switching from triple antiretroviral therapy (three-drug regimen; 3DR) to dolutegravir plus lamivudine (two-drug regimen; 2DR) was virologically non-inferior to continuing 3DR after 48 weeks of follow-up. Weight increased with 2DR relative to 3DR but it did not impact on metabolic parameters.

Methods

Multiomics plasma profile was performed to gain further insight into whether this therapy switch might affect specific biological pathways. DOLAM (EudraCT 201500027435) is a Phase 4, randomized, open-label, non-inferiority trial in which virologically suppressed persons with HIV treated with 3DR were assigned (1:1) to switch to 2DR or to continue 3DR for 48 weeks. Untargeted proteomics, metabolomics and lipidomics analyses were performed at baseline and at 48 weeks. Univariate and multivariate analyses were performed to identify changes in key molecules between both therapy arms.

Results

Switching from 3DR to 2DR showed a multiomic impact on circulating plasma concentration of N-acetylmuramoyl-L-alanine amidase (Q96PD5), insulin-like growth factor-binding protein 3 (A6XND0), alanine and triglyceride (TG) (48:0). Correlation analyses identified an association among the up-regulation of these four molecules in persons treated with 2DR.

Conclusions

Untargeted multiomics profiling studies identified molecular changes potentially associated with inflammation immune pathways, and with lipid and glucose metabolism. Although these changes could be associated with potential metabolic or cardiovascular consequences, their clinical significance remains uncertain. Further work is needed to confirm these findings and to assess their long-term clinical consequences.
The role of silver nanoparticles alone and combined with imipenem on carbapenem-resistant Klebsiella pneumoniae
Authors: Li Jiangyan , Yu Lian , Wang Ruirui , Lan Jiaqi , Li Ming , Qiao Yan , Tao Zhaoyu , Lü Hezuo , Wang Fengchao , Fang Qiang , Guo Pu
Published: March 2024

Aims

Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections poses a significant threat to human health, necessitating urgent development of new antimicrobial agents. Silver nanoparticles (AgNPs), which are among the most widely used engineered nanomaterials, have been extensively studied. However, the impact of AgNPs on CRKP and the potential for drug resistance development remain inadequately explored.

Methods and results

In this study, broth dilution method was used to determine the minimum inhibitory concentration (MIC) was determined using the broth dilution method. Results indicated MIC values of 93.1 ± 193.3 µg ml−1 for AgNPs, 2.3 ± 5.1 µg ml−1 for AgNO3, and 25.1 ± 48.3 µg ml−1 for imipenem (IMI). The combined inhibitory effect of AgNPs and IMI on CRKP was assessed using the checkerboard method. Moreover, after 6–20 generations of continuous culture, the MIC value of AgNPs increased 2-fold. Compared to IMI, resistance of Kl. pneumoniae to AgNPs developed more slowly, with a higher fold increase in MIC observed after 20 generations. Whole-genome sequencing revealed four nonsynonymous single nucleotide polymorphism mutations in CRKP after 20 generations of AgNP treatment.

Conclusion

We have demonstrated that AgNPs significantly inhibit CRKP isolates and enhance the antibacterial activity of imipenem against Kl. pneumoniae. Although the development of AgNP resistance is gradual, continued efforts are necessary for monitoring and studying the mechanisms of AgNP resistance.
The distortion and misinterpretation of TEM responses caused by the IP effect
Authors: Zhi Qingquan , Wang Xingchun , Wu Junjie , Li Xiu , Deng Xiaohong
Published: March 2024

Transient electromagnetic surveys are commonly conducted to map the distribution of resistivity, a key physical property in mineral exploration and other geological prospecting problems. However, the responses obtained in regions associated with chargeable minerals are always distorted by the induced polarization effects. In this study, the distorted responses are initially simulated in the frequency domain employing the Cole–Cole complex resistivity model and subsequently converted into the time domain through a time-frequency transformation method. A uniform half-space model is employed to validate the algorithm and illustrate the distortion characteristics of the responses in polarizable formations. A three-layer model is designed to estimate the misinterpretation of slightly complicated models. An actual misinterpretation is demonstrated by field responses containing induced polarization effects collected in the Wulong Gold Mine. The results show that the distortions under different geoelectrical conditions are consistent, enhancing the responses in the early stage and counteracting the responses in the late stage. The strong induced polarizable effects distort the responses by causing explicit sign reversals, whereas the weak induced polarizable effects only distort the decay rate of the responses. These distortions are prone to causing misinterpretations and resulting in excessively intricate geological structures.
Comparative analyses of the banded alder borer (Rosalia funebris) and Asian longhorned beetle (Anoplophora glabripennis) genomes reveal significant differences in genome architecture and gene content among these and other Cerambycidae
Authors: Sylvester Terrence , Adams Richard , Mitchell Robert F , Ray Ann M , Shen Rongrong , Shin Na Ra , McKenna Duane D
Published: March 2024

Rosalia funebris (RFUNE; Cerambycidae), the banded alder borer, is a longhorn beetle whose larvae feed on the wood of various economically and ecologically significant trees in western North America. Adults are short-lived and not known to consume plant material substantially. We sequenced, assembled, and annotated the RFUNE genome using HiFi and RNASeq data. We documented genome architecture and gene content, focusing on genes putatively involved in plant feeding (phytophagy). Comparisons were made to the well-studied genome of the Asian longhorned beetle (AGLAB; Anoplophora glabripennis) and other Cerambycidae. The 814 Mb RFUNE genome assembly was distributed across 42 contigs, with an N50 of 30.18 Mb. Repetitive sequences comprised 60.27% of the genome, and 99.0% of expected single-copy orthologous genes were fully assembled. We identified 12,657 genes, fewer than in the four other species studied, and 46.4% fewer than for Aromia moschata (same subfamily as RFUNE). Of the 7,258 orthogroups shared between RFUNE and AGLAB, 1,461 had more copies in AGLAB and 1,023 had more copies in RFUNE. We identified 240 genes in RFUNE that putatively arose via horizontal transfer events. The RFUNE genome encoded substantially fewer putative plant cell wall degrading enzymes than AGLAB, which may relate to the longer-lived plant-feeding adults of the latter species. The RFUNE genome provides new insights into cerambycid genome architecture and gene content and provides a new vantage point from which to study the evolution and genomic basis of phytophagy in beetles.
Eradicating gross tumor disease: a prerequisite for efficient radioimmunotherapy?
Authors: Deutsch Eric , Levy Antonin
Published: March 2024

Radiation therapy may induce off-target antitumor “abscopal” immunostimulatory and immunosuppressive effects. Several preclinical and early clinical studies revealed promising results when combining radiation therapy with immunostimulatory agents. Most radioimmunotherapy randomized trials showed disappointing results in patients with advanced tumors. In contrast, outcomes were encouraging when immunotherapy was delivered on top of gross disease elimination with curative-intent radiation therapy. In this review, we highlight available results from randomized trials and discuss the potential impact of overall tumor burden on the observed efficacy of radioimmunotherapy.
An 8-mm trocar-site hernia at a drainage insertion site after a three-port robotic myomectomy: case report and review of literature
Authors: Hong Yeon Hee , Paik Haerin , Kim Seul Ki , Lee Jung Ryeol , Suh Chang Suk
Published: March 2024

Trocar site hernia is a rare, serious operation-related complication after robotic gynecologic surgery. Here, we present two 8-mm port-site hernia cases after three-port robotic myomectomy with a review of reported previous cases. In the first case, small bowel obstruction was found postoperatively due to herniation at the left mid-axillary line 8-mm trocar site. Small bowel herniation through the same site as the first case was found in the second case. Emergency exploration was performed in both cases by extending the left trocar site. There was no sign of bowel ischemia, and successful bowel reduction and hernia repair were done. Unlike previously reported cases, these cases occurred in a normal body mass index (BMI) patient (first case 20.28 kg/m2, second case BMI 24.80 kg/m2) and were pelvic drain insertion sites. These sites were the weak points of the abdominal muscle coverage. Therefore, the closure of 8-mm trocar sites should be considered.
The PARADIGM project I: a multiscale radio morphological analysis of local U/LIRGS
Authors: Lucatelli Geferson , Beswick Robert J , Moldón Javier , Pérez-Torres Miguel A , Conway John E , Alberdi Antxon , Romero-Cañizales Cristina , Varenius Eskil , Klöckner Hans-Rainer , Barcos-Muñoz Loreto , Bondi Marco , Garrington Simon T , Aalto Susanne , Baan Willem A , Pihlström Ylva M
Published: March 2024

Disentangling the radio flux contribution from star formation (SF) and active-galactic-nuclei (AGNs) activity is a long-standing problem in extragalactic astronomy, since at frequencies of ≲ 10 GHz, both processes emit synchrotron radiation. We present in this work the general objectives of the PARADIGM (PAnchromatic high-Resolution Analysis of DIstant Galaxy Mergers) project, a multi-instrument concept to explore SF and mass assembly of galaxies. We introduce two novel general approaches for a detailed multiscale study of the radio emission in local (ultra) luminous infrared galaxies (U/LIRGs). In this work, we use archival interferometric data from the Very Large Array (VLA) centred at ∼ 6 GHz (C band) and present new observations from the e-Multi-Element Radio-Linked Interferometer Network (e-MERLIN) for UGC 5101, VV 705, VV 250, and UGC 8696. Using our image decomposition methods, we robustly disentangle the radio emission into distinct components by combining information from the two interferometric arrays. We use e-MERLIN as a probe of the core-compact radio emission (AGN or starburst) at ∼ 20 pc scales, and as a probe of nuclear diffuse emission, at scales ∼100–200 pc. With VLA, we characterize the source morphology and the flux density on scales from ∼200 pc up to and above 1 kpc. As a result, we find deconvolved and convolved sizes for nuclear regions from ∼10 to ∼200 pc. At larger scales, we find sizes of 1.5–2 kpc for diffuse structures (with effective sizes of ∼ 300–400 pc). We demonstrate that the radio emission from nuclear extended structures (∼ 100 pc) can dominate over core-compact components, providing a significant fraction of the total multiscale SF output. We establish a multiscale radio tracer for SF by combining information from different instruments. Consequently, this work sets a starting point to potentially correct for overestimations of AGN fractions and underestimates of SF activity.
Neutron star – white dwarf binaries: probing formation pathways and natal kicks with LISA
Authors: Korol Valeriya , Igoshev Andrei P , Toonen Silvia , Karnesis Nikolaos , Moore Christopher J , Finch Eliot , Klein Antoine
Published: March 2024

Neutron star–white dwarf (NS + WD) binaries offer a unique opportunity for studying NS-specific phenomena with gravitational waves. In this paper, we employ the binary population synthesis technique to study the Galactic population of NS + WD binaries with the future Laser Interferometer Space Antenna (LISA). We anticipate approximately $\mathcal {O}(10^2)$ detectable NS + WD binaries by LISA, encompassing both circular and eccentric ones formed via different pathways. Despite the challenge of distinguishing these binaries from more prevalent double white dwarfs (especially at frequencies below 2 mHz), we show that their eccentricity and chirp mass distributions may provide avenues to explore the NS natal kicks and common envelope evolution. Additionally, we investigate the spatial distribution of detectable NS + WD binaries relative to the Galactic plane and discuss prospects for identifying electromagnetic counterparts at radio wavelengths. Our results emphasise LISA’s capability to detect and characterize NS + WD binaries and to offer insights into the properties of the underlying population. Our conclusions carry significant implications for shaping LISA data analysis strategies and future data interpretation.