bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neisseria gonorrhoeae
scavenges host sialic acid for Siglec-mediated, complement-independent suppression of neutrophil activation
Authors: Cardenas Amaris J. , Thomas Keena S. , Broden Mary W. , Ferraro Noel J. , Pires Marcos M. , John Constance M. , Jarvis Gary A. , Criss Alison K. 
Published: April 2024

ABSTRACT

Gonorrhea, caused by the bacterium
Neisseria gonorrhoeae
(Gc), is characterized by neutrophilic influx to infection sites. Gc has developed mechanisms to resist killing by neutrophils that include modifications to its surface lipooligosaccharide (LOS). One such LOS modification is sialylation: Gc sialylates its terminal LOS sugars with cytidine-5′-monophosphate-
N
-acetylneuraminic acid, which is scavenged from the host using LOS sialyltransferase (Lst) since Gc cannot make its sialic acid. Sialylation enables sensitive strains of Gc to resist complement-mediated killing in a serum-dependent manner. However, little is known about the contribution of sialylation to complement-independent, direct Gc-neutrophil interactions. In the absence of complement, we found sialylated Gc expressing opacity-associated (Opa) proteins decreased the oxidative burst and granule exocytosis from primary human neutrophils. In addition, sialylated Opa+ Gc survived better than vehicle treated or Δ
lst
Gc when challenged with neutrophils. However, Gc sialylation did not significantly affect Opa-dependent association with or internalization of Gc by neutrophils. Previous studies have implicated sialic acid-binding immunoglobulin-type lectins (Siglecs) in modulating neutrophil interactions with sialylated Gc. Blocking neutrophil Siglecs with antibodies that bind to their extracellular domains eliminated the ability of sialylated Opa+ Gc to suppress the oxidative burst and resist neutrophil killing. These findings highlight a new role for sialylation in Gc evasion of human innate immunity, with implications for the development of vaccines and therapeutics for gonorrhea.

IMPORTANCE

Neisseria gonorrhoeae
, the bacterium that causes gonorrhea, is an urgent global health concern due to increasing infection rates, widespread antibiotic resistance, and its ability to thwart protective immune responses. The mechanisms by which Gc subverts protective immune responses remain poorly characterized. One way
N. gonorrhoeae
evades human immunity is by adding sialic acid that is scavenged from the host onto its lipooligosaccharide, using the sialyltransferase Lst. Here, we found that sialylation enhances
N. gonorrhoeae
survival from neutrophil assault and inhibits neutrophil activation, independently of the complement system. Our results implicate bacterial binding of sialic acid-binding lectins (Siglecs) on the neutrophil surface, which dampens neutrophil antimicrobial responses. This work identifies a new role for sialylation in protecting
N. gonorrhoeae
from cellular innate immunity, which can be targeted to enhance the human immune response in gonorrhea.
Synchronous subarachnoid haemorrhage and ischaemic stroke as a result of complete internal carotid artery occlusion
Authors: Gomaa Aysha , Biyanwila Chemindra , Jantre Mansi 
Published: April 2024

A previously healthy man in his 60s presents with a one-day history of insidious onset headache and ‘walking into doors’. He reported transient right arm pain and tingling but no weakness. A CT brain showed a right middle cerebral artery (MCA) infarct as well as a synchronous right frontal lobe convexal subarachnoid haemorrhage (cSAH). An arch to vertex CT angiogram demonstrated right MCA occlusion and complete right internal carotid artery (ICA) occlusion from its origin. Reconstitution of flow was seen within the distal right ICA at the level of the distal foramen lacerum. A repeat CT of the brain after one week showed a stable appearance of the bleeding and infarct. He was commenced on antiplatelet therapy for the treatment of the ischaemic stroke as well as secondary prevention.This is a rare case of synchronous right MCA infarct as well as a right frontal cSAH secondary to ipsilateral carotid artery occlusion.
Impact of a pandemic shock on unmet medical needs of middle-aged and older adults in 10 countries
Authors: Guo Chao , Yuan Dianqi , Tang Huameng , Hu Xiyuan , Lei Yiyang 
Published: April 2024

ObjectiveThe objective is to explore the impact of the pandemic shock on the unmet medical needs of middle-aged and older adults worldwide.MethodsThe COVID-19 pandemic starting in 2020 was used as a quasiexperiment. Exposure to the pandemic was defined based on an individual’s context within the global pandemic. Data were obtained from the Integrated Values Surveys. A total of 11 932 middle-aged and older adults aged 45 years and above from 10 countries where the surveys conducted two times during 2011 and 2022 were analysed. We used logistic regression models with the difference-in-difference method to estimate the impact of pandemic exposure on unmet medical needs by comparing differences before and after the pandemic across areas with varying degrees of severity.ResultsAmong the 11 932 middle-aged and older adults, 3647 reported unmet medical needs, with a pooled unmet rate of 30.56% (95% CI: 29.74% to 31.40%). The pandemic significantly increased the risk of unmet medical needs among middle-aged and older adults (OR: 2.33, 95% CI: 1.94 to 2.79). The deleterious effect of the pandemic on unmet medical needs was prevalent among middle-aged adults (2.53, 2.00 to 3.20) and older adults (2.00, 1.48 to 2.69), as well as among men (2.24, 1.74 to 2.90) and women (2.34, 1.82 to 3.03). The results remained robust in a series of sensitivity analyses.ConclusionThese findings suggest that efforts should be made by policymakers and healthcare professionals to balance healthcare resources to adequately address the comprehensive healthcare demands of individuals regarding multiple health issues, taking into account the challenges posed by pandemics.
Call me Ishmael: addressing the white whale of team communication in the operating room with labelled surgical caps at an academic medical centre
Authors: Goldhaber Nicole Hamilton , Mehta Shivani , Longhurst Christopher A , Malachowski Elizabeth , Jones Melissa , Clary Bryan M , Schaefer Robin L , McHale Michael , Rhodes Lisa P , Mekeel Kristin L , Reeves J Jeffery 
Published: April 2024

IntroductionEffective communication in the operating room (OR) is crucial. Addressing a colleague by their name is respectful, humanising, entrusting and associated with improved clinical outcomes. We aimed to enhance team communication in the perioperative environment by offering personalised surgical caps labelled with name and provider role to all OR team members at a large academic medical centre.Materials and methodsThis was a quasi-experimental, uncontrolled, before-and-after quality improvement study. A survey regarding perceptions of team communication, knowledge of names and roles, communication barriers, and culture was administered before and after cap delivery. Survey results were measured on a 5-point Likert Scale; descriptive statistics and mean scores were compared. All cause National Surgical Quality Improvement Project (NSQIP) morbidity and mortality outcomes for surgical specialties were examined.Results1420 caps were delivered across the institution. Mean survey scores increased for knowing the names and roles of providers around the OR, feeling that people know my name and feeling comfortable communicating without barriers across disciplines. The mean score for team communication around the OR is excellent was unchanged. The highest score both before and after was knowing the name of an interdisciplinary team member is important for patient care. A total of 383 and 212 providers participated in the study before and after cap delivery, respectively. Participants agreed or strongly agreed that labelled surgical caps made it easier to talk to colleagues (64.9%) while improving communication (66.0%), team culture (60.5%) and patient care (56.8%). No significant differences were noted in NSQIP outcomes.ConclusionsPersonalised labelled surgical caps are a simple, inexpensive tool that demonstrates promise in improving perioperative team communication. Creating highly reliable surgical teams with optimal communication channels requires a multifaceted approach with engaged leadership, empowered front-line providers and an institutional commitment to continuous process improvement.
Modeling and correction of image drift in dynamic shadowgraphy experiments
Authors: Castellini Stefano , Brizioli Matteo , Giraudet Cédric , Carpineti Marina , Croccolo Fabrizio , Giavazzi Fabio , Vailati Alberto 
Published: April 2024

Abstract
The study of phoretic transport phenomena under non-stationary conditions presents several challenges, mostly related to the stability of the experimental apparatus. This is particularly true when investigating with optical means the subtle temperature and concentration fluctuations that arise during diffusion processes, superimposed to the macroscopic state of the system. Under these conditions, the tenuous signal from fluctuations is easily altered by the presence of artifacts. Here, we address an experimental issue frequently reported in the investigation by means of dynamic shadowgraphy of the non-equilibrium fluctuations arising in liquid mixtures under non-stationary conditions, such as those arising after the imposition or removal of a thermal stress, where experiments show systematically the presence of a spurious contribution in the reconstructed structure function of the fluctuations, which depends quadratically from the time delay. We clarify the mechanisms responsible for this artifact, showing that it is caused by the imperfect alignment of the sample cell with respect to gravity, which couples the temporal evolution of the concentration profile within the sample with the optical signal collected by the shadowgraph diagnostics. We propose a data analysis protocol that enables disentangling the spurious contributions and the genuine dynamics of the fluctuations, which can be thus reliably reconstructed.

Graphic Abstract
The imposition of a thermal gradient across a liquid mixture results in a time-dependent refractive index distribution. In the presence of a misalignment of the confining cell with respect to gravity, this leads to a deflection of the optical probe beam used to monitor concentration fluctuations within the sample in quantitative shadowgraphy experiments. If not properly accounted for, this effect can introduce a significant bias in the optical signal.
Charm physics
Authors: Petrov Alexey A. 
Published: April 2024

AbstractWe review recent developments in charm physics, focusing on the physics of charmed mesons. We discuss recent progress in charm spectroscopy and the multitude of mesonic and baryonic exotic states containing charm quarks. We review searches for new physics with charmed mesons with rare decays. We also touch upon recent theoretical and experimental progress in searches for CP-violation in charm decays and the status of $$D^0-\overline{D}{}^0$$

D
0

-

D
¯

0

mixing.
R-Blocks: an Energy-Efficient, Flexible, and Programmable CGRA
Authors: de Bruin Barry , Vadivel Kanishkan , Wijtvliet Mark , Jääskeläinen Pekka , Corporaal Henk 
Published: April 2024

Emerging data-driven applications in the embedded, e-Health, and internet of things (IoT) domain require complex on-device signal analysis and data reduction to maximize energy efficiency on these energy-constrained devices. Coarse-grained reconfigurable architectures (CGRAs) have been proposed as a good compromise between flexibility and energy efficiency for ultra-low power (ULP) signal processing. Existing CGRAs are often specialized and domain-specific or can only accelerate simple kernels, which makes accelerating complete applications on a CGRA while maintaining high energy efficiency an open issue. Moreover, the lack of instruction set architecture (ISA) standardization across CGRAs makes code generation using current compiler technology a major challenge. This work introduces R-Blocks; a ULP CGRA with HW/SW co-design tool-flow based on the OpenASIP toolset. This CGRA is extremely flexible due to its well-established VLIW-SIMD execution model and support for flexible SIMD-processing, while maintaining an extremely high energy efficiency using software bypassing, optimized instruction delivery, and local scratchpad memories. R-Blocks is synthesized in a commercial 22-nm FD-SOI technology and achieves a full-system energy efficiency of 115 MOPS/mW on a common FFT benchmark, 1.45× higher than a highly tuned embedded RISC-V processor. Comparable energy efficiency is obtained on multiple complex workloads, making R-Blocks a promising acceleration target for general-purpose computing.
Transfer Learning Reveals Cancer-Associated Fibroblasts Are Associated with Epithelial–Mesenchymal Transition and Inflammation in Cancer Cells in Pancreatic Ductal Adenocarcinoma
Authors: Guinn Samantha , Kinny-Köster Benedict , Tandurella Joseph A. , Mitchell Jacob T. , Sidiropoulos Dimitrios N. , Loth Melanie , Lyman Melissa R. , Pucsek Alexandra B. , Zabransky Daniel J. , Lee Jae W. , Kartalia Emma , Ramani Mili , Seppälä Toni T. , Cherry Christopher , Suri Reecha , Zlomke Haley , Patel Jignasha , He Jin , Wolfgang Christopher L. , Yu Jun , Zheng Lei , Ryan David P. , Ting David T. , Kimmelman Alec , Gupta Anuj , Danilova Ludmila , Elisseeff Jennifer H. , Wood Laura D. , Stein-O'Brien Genevieve , Kagohara Luciane T. , Jaffee Elizabeth M. , Burkhart Richard A. , Fertig Elana J. , Zimmerman Jacquelyn W. 
Published: April 2024

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy characterized by an immunosuppressive tumor microenvironment enriched with cancer-associated fibroblasts (CAF). This study used a convergence approach to identify tumor cell and CAF interactions through the integration of single-cell data from human tumors with human organoid coculture experiments. Analysis of a comprehensive atlas of PDAC single-cell RNA sequencing data indicated that CAF density is associated with increased inflammation and epithelial–mesenchymal transition (EMT) in epithelial cells. Transfer learning using transcriptional data from patient-derived organoid and CAF cocultures provided in silico validation of CAF induction of inflammatory and EMT epithelial cell states. Further experimental validation in cocultures demonstrated integrin beta 1 (ITGB1) and vascular endothelial factor A (VEGFA) interactions with neuropilin-1 mediating CAF-epithelial cell cross-talk. Together, this study introduces transfer learning from human single-cell data to organoid coculture analyses for experimental validation of discoveries of cell–cell cross-talk and identifies fibroblast-mediated regulation of EMT and inflammation.

Significance:
Adaptation of transfer learning to relate human single-cell RNA sequencing data to organoid-CAF cocultures facilitates discovery of human pancreatic cancer intercellular interactions and uncovers cross-talk between CAFs and tumor cells through VEGFA and ITGB1.
Oncogene-Driven Non–Small Cell Lung Cancers in Patients with a History of Smoking Lack Smoking-Induced Mutations
Authors: Huang Chen-Yang , Jiang Nanhai , Shen Meixin , Lai Gillianne G. , Tan Aaron C. , Jain Amit , Saw Stephanie P. , Ang Mei Kim , Ng Quan Sing , Lim Darren W. , Kanesvaran Ravindran , Tan Eng Huat , Tan Wan Ling , Ong Boon-Hean , Chua Kevin L. , Anantham Devanand , Takano Angela M. , Lim Kiat Hon , Tam Wai Leong , Sim Ngak Leng , Skanderup Anders J. , Tan Daniel S. , Rozen Steven G. 
Published: April 2024

Abstract

Non–small cell lung cancers (NSCLC) in nonsmokers are mostly driven by mutations in the oncogenes EGFR, ERBB2, and MET and fusions involving ALK and RET. In addition to occurring in nonsmokers, alterations in these “nonsmoking-related oncogenes” (NSRO) also occur in smokers. To better understand the clonal architecture and genomic landscape of NSRO-driven tumors in smokers compared with typical-smoking NSCLCs, we investigated genomic and transcriptomic alterations in 173 tumor sectors from 48 NSCLC patients. NSRO-driven NSCLCs in smokers and nonsmokers had similar genomic landscapes. Surprisingly, even in patients with prominent smoking histories, the mutational signature caused by tobacco smoking was essentially absent in NSRO-driven NSCLCs, which was confirmed in two large NSCLC data sets from other geographic regions. However, NSRO-driven NSCLCs in smokers had higher transcriptomic activities related to the regulation of the cell cycle. These findings suggest that, whereas the genomic landscape is similar between NSRO-driven NSCLC in smokers and nonsmokers, smoking still affects the tumor phenotype independently of genomic alterations.

Significance:
Non-small cell lung cancers driven by nonsmoking-related oncogenes do not harbor genomic scars caused by smoking regardless of smoking history, indicating that the impact of smoking on these tumors is mainly nongenomic.
Ketogenic Diet Alters the Epigenetic and Immune Landscape of Prostate Cancer to Overcome Resistance to Immune Checkpoint Blockade Therapy
Authors: Murphy Sean , Rahmy Sharif , Gan Dailin , Liu Guoqiang , Zhu Yini , Manyak Maxim , Duong Loan , He Jianping , Schofield James H. , Schafer Zachary T. , Li Jun , Lu Xuemin , Lu Xin 
Published: April 2024

Abstract

Resistance to immune checkpoint blockade (ICB) therapy represents a formidable clinical challenge limiting the efficacy of immunotherapy. In particular, prostate cancer poses a challenge for ICB therapy due to its immunosuppressive features. A ketogenic diet (KD) has been reported to enhance response to ICB therapy in some other cancer models. However, adverse effects associated with continuous KD were also observed, demanding better mechanistic understanding and optimized regimens for using KD as an immunotherapy sensitizer. In this study, we established a series of ICB-resistant prostate cancer cell lines and developed a highly effective strategy of combining anti-PD1 and anti-CTLA4 antibodies with histone deacetylase inhibitor (HDACi) vorinostat, a cyclic KD (CKD), or dietary supplementation of the ketone body β-hydroxybutyrate (BHB), which is an endogenous HDACi. CKD and BHB supplementation each delayed prostate cancer tumor growth as monotherapy, and both BHB and adaptive immunity were required for the antitumor activity of CKD. Single-cell transcriptomic and proteomic profiling revealed that HDACi and ketogenesis enhanced ICB efficacy through both cancer cell–intrinsic mechanisms, including upregulation of MHC class I molecules, and -extrinsic mechanisms, such as CD8+ T-cell chemoattraction, M1/M2 macrophage rebalancing, monocyte differentiation toward antigen-presenting cells, and diminished neutrophil infiltration. Overall, these findings illuminate a potential clinical path of using HDACi and optimized KD regimens to enhance ICB therapy for prostate cancer.

Significance:
Optimized cyclic ketogenic diet and 1,3-butanediol supplementation regimens enhance the efficacy of immune checkpoint blockade in prostate cancer through epigenetic and immune modulations, providing dietary interventions to sensitize tumors to immunotherapy.
How Artificial Intelligence Unravels the Complex Web of Cancer Drug Response
Authors: Elemento Olivier 
Published: April 2024

Abstract
The intersection of precision medicine and artificial intelligence (AI) holds profound implications for cancer treatment, with the potential to significantly advance our understanding of drug responses based on the intricate architecture of tumor cells. A recent study by Park and colleagues titled “A Deep Learning Model of Tumor Cell Architecture Elucidates Response and Resistance to CDK4/6 Inhibitors” epitomizes this intersection by leveraging an interpretable deep learning model grounded in a comprehensive map of multiprotein assemblies in cancer, known as Nested Systems in Tumors. This study not only elucidates mechanisms underlying the response to CDK4/6 inhibitors in breast cancer therapy but also highlights the critical role of model interpretability leading to new mechanistic insights.
Early Serial Assessment of Aggregate Vasoactive Support and Mortality in Cardiogenic Shock: Insights From the Critical Care Cardiology Trials Network Registry
Authors: Patel Siddharth M. , Berg David D. , Bohula Erin A. , Baird-Zars Vivian M. , Barsness Gregory W. , Chaudhry Sunit-Preet , Chonde Meshe D. , Cooper Howard A. , Ginder Curtis , Jentzer Jacob C. , Kontos Michael C. , Miller P. Elliott , Newby L. Kristin , O’Brien Connor G. , Park Jeong-Gun , Pierce Matthew J. , Pisani Barbara A. , Potter Brian J. , Shah Kevin S. , Teuteberg Jeffrey J. , Katz Jason N. , van Diepen Sean , Morrow David A. 
Published: April 2024

BACKGROUND:
Associations of early changes in vasoactive support with cardiogenic shock (CS) mortality remain incompletely defined.

METHODS:
The Critical Care Cardiology Trials Network is a multicenter registry of cardiac intensive care units. Patients admitted with CS (2018–2023) had vasoactive dosing assessed at 4 and 24 hours from cardiac intensive care unit admission and quantified by the vasoactive-inotropic score (VIS). Prognostic associations of VIS at both time points, as well as change in VIS from 4 to 24 hours, were examined. Interaction testing was performed based on mechanical circulatory support status.

RESULTS:

Among 3665 patients, 82% had a change in VIS <10, with 7% and 11% having a ≥10-point increase and decrease from 4 to 24 hours, respectively. The 4 and 24-hour VIS were each associated with cardiac intensive care unit mortality (13%–45% and 11%–73% for VIS <10 to ≥40, respectively;
P
trend
<0.0001 for each). Stratifying by the 4-hour VIS, changes in VIS from 4 to 24 hours had a graded association with mortality, ranging from a 2- to >4-fold difference in mortality comparing those with a ≥10-point increase to ≥10-point decrease in VIS (
P
trend
<0.0001). The change in VIS alone provided good discrimination of cardiac intensive care unit mortality (C-statistic, 0.72 [95% CI, 0.70–0.75]) and improved discrimination of the 24-hour Sequential Organ Failure Assessment score (0.72 [95% CI, 0.69–0.74] to 0.76 [95% CI, 0.74–0.78]) and the clinician-assessed Society for Cardiovascular Angiography and Interventions shock stage (0.72 [95% CI, 0.70–0.74] to 0.77 [95% CI, 0.75–0.79]). Although present in both groups, the mortality risk associated with VIS was attenuated in patients managed with versus without mechanical circulatory support (odds ratio per 10-point higher 24-hour VIS, 1.36 [95% CI, 1.23–1.49] versus 1.84 [95% CI, 1.69–2.01];
P
interaction
<0.0001).

CONCLUSIONS:
Early changes in the magnitude of vasoactive support in CS are associated with a gradient of risk for mortality. These data suggest that early VIS trajectory may improve CS prognostication, with the potential to be leveraged for clinical decision-making and research applications in CS.