bluuebunny/crossref_metadata_2025 huggingface dataset:
A cycle of complications: a case report on trastuzumab-induced takotsubo cardiomyopathy causing left ventricular thrombosis complicated by thromboembolic stroke
Authors: Patel Vidhi , Okan Tetyana , Yee Jia L , Patel Jagruti
Published: January 2025

Background

Left ventricular thrombus (LVT) formation is an uncommon phenomenon, typically observed in acute cardiac settings and hypercoagulable states. Takotsubo cardiomyopathy (TC) is a reversible condition originally thought to be linked to immense emotional stress. The occurrence of chemotherapy-related cardiotoxicity presenting with TC and LVT formation is a relatively new concept that remains not fully understood.

Case summary

We present the case of a 77-year-old woman with Stage IV breast cancer being treated with trastuzumab and capecitabine therapy, who presented to our hospital with symptoms of right-sided weakness, facial droop, and slurred speech. She was admitted for acute left frontal lobe infarction due to an occluded distal left posterior M2 branch of the left middle cerebral artery. As part of thromboembolic stroke work-up, transthoracic echocardiogram (TTE) was obtained, which showed moderately to severely decreased left ventricular systolic function (LVEF 35%) with wall motion abnormalities suggestive of TC and a 0.9 × 1 cm echogenic structure in the LV consistent with LVT. She was started on therapeutic anticoagulation and was discharged on oral warfarin with international normalized ratio (INR) goal of 2-3. Both capecitabine and trastuzumab were held during her hospitalization. Repeat TTE after 2 weeks showed an LVEF of 60% with normal LV systolic function and absence of any LVT. Symptoms-wise her right-sided weakness was improving. She was continued on capecitabine and warfarin for now, and continued to follow-up outpatient with oncology, cardiology and neurology.

Discussion

This case highlights TC and LVT as rare but life-threatening complications of trastuzumab-induced cardiotoxicity. We emphasize the importance of early diagnosis to prevent further complications, such as acute thromboembolic stroke, and the necessity of prompt therapeutic interventions to reduce morbidity and mortality. Additionally, we address the multifactorial aetiology of TC and the need for frequent TTE monitoring in patients undergoing trastuzumab therapy to diagnose these complications early.
Epicardial connection between superior vena cava and right atrium contributes to subsequent atrial fibrillation: a case report
Authors: Otsubo Shunya , Takemoto Masao , Nyuta Eiji , Tsuchihashi Takuya
Published: January 2025

Background

The superior vena cava (SVC) acts as a non-pulmonary vein (PV) trigger for atrial fibrillation (AF) in 2%–6% of patients and harbours 25%–40% of non-PV foci. Approximately 10% of patients with AF have epicardial connections (ECs) between the atrium and PV inside the PV isolation lines, which are associated with AF recurrence. However, the contribution of EC(s) between the SVC and right atrium (RA) to subsequent AF remains unknown.

Case summary

A 76-year-old woman underwent ablation for recurrent AF. She had undergone cryo-balloon ablation for paroxysmal AF 3 years previously. After confirming the complete entrance and exit blocks of the four PVs, SVC firing-induced AF was observed. After SVC isolation, the EC between the SVC and RA was observed. No AF was induced after EC ablation.

Discussion

Although the mechanisms of ECs in the SVC and RA have not been entirely elucidated, several potential mechanisms have been proposed. (i) Anatomically inherited myofibres/bundles may run through the epicardial side between the SVC and RA. (ii) Epicardial connections between the right PV and the SVC or RA have been recently reported. Thus, we might speculate on the possibility of the existence of EC(s) between the right PV and both the SVC and RA. After cryoablation in the first session, the connection between the SVC and RA remained, which might have acted as EC(s). Thus, physicians should consider the possibility of EC(s) when remaining potentials in the SVC are observed, even though the SVC isolation line seems to be completed.
Chemical structure of lipoteichoic acid in the probiotic strain Latilactobacillus curvatus CP2998
Authors: Shiraishi Tsukasa , Katsuki Ryo , Kumeta Hiroyuki , Sakata Shinji , Yokota Shin-ichi
Published: January 2025

Latilactobacillus curvatus, found in various fermented foods, is a promising probiotic with unique health benefits. Lipoteichoic acid (LTA) is a characteristic amphiphilic surface polymer of Gram-positive bacteria and exhibits immunomodulatory activities. Despite the structural diversity of LTA among different bacterial species and strains, no information is available on the chemical structure of LTA in L. curvatus. In this study, we aimed to determine the structure of LTA isolated from L. curvatus CP2998. One- and two-dimensional nuclear magnetic resonance spectra of intact LTA revealed that LTA had a glycerolphosphate polymer as a hydrophilic main chain with partial substitutions of α-linked glucose and d-alanine at the hydroxy group at position 2 of the glycerol residue. The anchor glycolipid fraction was obtained by hydrofluoric acid treatment. Matrix-assisted laser desorption ionization-time-of-flight mass spectrometry spectrum of the anchor glycolipid revealed that it contained diglucosyldiacylglycerol and diglucosylmonoacylglycerol. Our results suggest that L. curvatus CP2998 possesses a typical type I LTA structure; however, the lactic acid bacteria-specific anchor glycolipid structures, such as tri- or tetra-saccharides and three fatty acid residues, were not identified.
Radical Right Dystopias in the Global Culture Wars
Authors: Abrahamsen Rita , Williams Michael C
Published: January 2025

Despite the pervasive description of our times as dystopian, the disciplines of political theory and international relations seldom consider the political power of dystopian imaginaries. This article seeks to remedy this neglect by focusing on the radical Right's invocation of dystopias. These dystopian narratives go beyond mere scaremongering and constitute instead “critical dystopias” that follow a distinct grammar rooted in the radical Right's ideological critique of managerialism and liberal globalization. They express the radical Right's fear of liberalism, exploiting the latent dystopian possibilities in the liberal present. Promoted by right-wing influencers and media pundits, critical dystopias translate theoretical and ideological interpretations of social and political life into globally mobile, everyday infotainment readily accessible to broader, global audiences. As such, radical Right dystopias are affective strategies in a global culture war that may help (re)produce and reinforce political subjectivities, identities, and geopolitical imaginaries. They provide a window on the global appeal and interconnectedness of the radical Right and serve as a reminder of the importance of emotions and affect in international politics.
Adaptation of the WHO AWaRe (Access, Watch, Reserve) antibiotic classification to support national antimicrobial stewardship priorities in the UK: findings from a modified Delphi approach to achieve expert consensus
Authors: Bou-Antoun Sabine , Oettle Rebecca C , Leanord Alistair , Seaton Ronald Andrew , Cooper Ben S , Muller-Pebody Berit , Conlon-Bingham Geraldine , Kerr Frances , Hand Kieran S , Sandoe Jonathan A T , Llewelyn Martin J , Fleming Naomi , Brown Nicholas M , Reid Nicholas , Howard Philip , Mckinstry Sarah-Jayne , Malcolm William , Demirjian Alicia , Ashiru-Oredope Diane
Published: January 2025

Objectives

In 2017, the WHO introduced the AWaRe (Access, Watch and Reserve) classification of antibiotics to support antibiotic stewardship (AMS) at local, national and global levels. We assessed the categorization of each of the antibiotics for systemic use for antimicrobial stewardship and quality improvement practice across primary and secondary care in the UK, proposing a nationally adapted UK-AWaRe classification.

Methods

A four-stage modified Delphi survey was conducted to review the AWaRe classifications in light of antibiotic resistance profiles, antibiotic use and stewardship practice in the UK. Recommendations were iteratively discussed and consensus reached on how to adapt the WHO AWaRe list. Implications of the proposed new categorization for possible antibiotic usage targets were assessed using England national antibiotic consumption data as a case study.

Results

Sixty-one experts across the four UK nations participated in the modified Delphi process. Consensus was most easily reached, with least between-expert variation, for Access antibiotics. Seventeen antibiotics differed in categorization when comparing proposed adapted UK-AWaRe classification and the 2023 WHO AWaRe classification. Through the focus group discussions, the importance of clear messaging was highlighted for the proposed move of first-generation cephalosporins into the Access category, a step-change from the 2019 England AWaRe classification, where all cephalosporins were in the Watch category. From the case study analysis of national data in England, Access antibiotics accounted for >60% of human antibiotic use between 2018 and 2022, 69.7% when using the WHO 2023 classification and 63.7% with the proposed UK-adapted 2024 classification.

Conclusions

An adapted UK-AWaRe list has been suggested through a consensus-reaching process. This will support national AMS and antibiotic usage targets of the UK antimicrobial resistance 2024–29 national action plan.
Operation Baby Drop: Lessons Learned From Military International Air Transport of Critically Ill Neonate
Authors: Mullin Kaitlyn , Okonek Elizabeth , Krick Jeanne
Published: January 2025

Military medical transport is unique due to its frequent long-distance travel with limited supplies and capabilities. Military neonatal transport is perhaps even more niche, and descriptions in the literature are rare. A military neonatal team transported a 1-month-old former 26-week infant from a forward-deployed non-combat setting. Due to complications in-flight, the infant could only be safely transported from the deployed setting to the refueling stop. This report is a descriptive analysis of the transport, including lessons learned that may help future teams plan for possible complications that can occur during neonatal transports.
Tracing star formation across cosmic time at tens of parsec-scales in the lensing cluster field Abell 2744
Authors: Claeyssens Adélaïde , Adamo Angela , Messa Matteo , Dessauges-Zavadsky Miroslava , Richard Johan , Kramarenko Ivan , Matthee Jorryt , Naidu Rohan P
Published: January 2025

We present a sample of 1956 individual stellar clumps at redshift $0.7\lt z\lt 10$, detected with JWST/NIRCam in 476 galaxies lensed by the galaxy cluster Abell2744. The lensed clumps present magnifications ranging between $\mu$ = 1.8 and $\mu$ = 300. We perform simultaneous size-photometry estimates in 20 JWST/NIRCam median and broad-band filters from 0.7 to 5 $\mu$m. Spectral energy distribution (SED) fitting analyses enable us to recover the physical properties of the clumps. The majority of the clumps are spatially resolved and have effective radii in the range $\rm {\it R}_{eff} = 10 {\!-\!} 700 \ pc$. We restrict this first study to the 1751 post-reionization era clumps with redshift $\lt 5.5$. We find a significant evolution of the average clump ages, star formation rates (SFRs), SFR surface densities, and metallicity with increasing redshift, while median stellar mass and stellar mass surface densities are similar in the probed redshift range. We observe a strong correlation between the clump properties and the properties of their host galaxies, with more massive galaxies hosting more massive and older clumps. We find that clumps closer to their host galactic centre are on average more massive, while their ages do not show clear sign of migration. We find that clumps at cosmic noon sample the upper-mass end of the mass function to higher masses than at $z\gt 3$, reflecting the rapid increase towards the peak of the cosmic star formation history. We conclude that the results achieved over the studied redshift range are in agreement with expectation of in situ clump formation scenario from large-scale disc fragmentation.
Fully comprehensive diagnostic of galaxy activity using principal components of visible spectra: implementation on nearby S0s
Authors: Tous J L , Solanes J M , Perea J D
Published: January 2025

We introduce a novel galaxy classification methodology based on the visible spectra of a sample of over 68 000 nearby ($z\le 0.1$) Sloan Digital Sky Survey lenticular (S0) galaxies. Unlike traditional diagnostic diagrams, which rely on a limited set of emission lines and class dividers to identify ionizing sources, our approach provides a comprehensive framework for characterizing galaxies regardless of their activity level. By projecting galaxies into the 2D latent space defined by the first three principal components (PCs) of their entire visible spectra, our method remains robust even when data from individual emission lines are missing. We employ Gaussian kernel density estimates of the classical Baldwin–Phillips–Terlevich (BPT) activity classes in the new classification subspace, adjusted according to their relative abundance in our S0 sample, to generate probability maps for star-forming, Seyfert, composite, and low-ionization nuclear emission-line region (LINER) galaxies. These maps closely mirror the canonical distribution of BPT classes shown by the entire galaxy population, demonstrating that our PC-based taxonomy effectively predicts the dominant ionizing mechanisms through a probabilistic approach that provides a realistic reflection of galaxy activity and allows for refined class membership. Our analysis further reveals that flux-limited BPT-like diagrams are inherently biased against composite and star-forming galaxies due to their weaker [O iii] emission. Besides, it suggests that although most low-activity galaxies excluded from these diagnostics exhibit visual spectra with LINER-like characteristics, their remaining activity is likely driven by mechanisms unrelated to either star formation or supermassive black hole accretion. A machine-readable catalogue listing BPT-class probabilities for the galaxies analysed is publicly released with this article.
Mapping the spatial atlas of the human bone tissue integrating spatial and single-cell transcriptomics
Authors: Lin Weiqiang , Li Yisu , Qiu Chuan , Zou Binghao , Gong Yun , Zhang Xiao , Tian Di , Sherman William , Sanchez Fernando , Wu Di , Su Kuan-Jui , Xiao Xinyi , Luo Zhe , Tian Qing , Chen Yiping , Shen Hui , Deng Hongwen
Published: January 2025

Bone is a multifaceted tissue requiring orchestrated interplays of diverse cells within specialized microenvironments. Although significant progress has been made in understanding cellular and molecular mechanisms of component cells of bone, revealing their spatial organization and interactions in native bone tissue microenvironment is crucial for advancing precision medicine, as they govern fundamental signaling pathways and functional dependencies among various bone cells. In this study, we present the first integrative high-resolution map of human bone and bone marrow, using spatial and single-cell transcriptomics profiling from femoral tissue. This multi-modal approach discovered a novel bone formation-specialized niche enriched with osteoblastic lineage cells and fibroblasts and unveiled critical cell–cell communications and co-localization patterns between osteoblastic lineage cells and other cells. Furthermore, we discovered a novel spatial gradient of cellular composition, gene expression and signaling pathway activities radiating from the trabecular bone. This comprehensive atlas delineates the intricate bone cellular architecture and illuminates key molecular processes and dependencies among cells that coordinate bone metabolism. In sum, our study provides an essential reference for the field of bone biology and lays the foundation for advanced mechanistic studies and precision medicine approaches in bone-related disorders.
Embedding a ribonuclease in the spore crust couples gene expression to spore development in Bacillus subtilis
Authors: D’Halluin Alexandre , Gilet Laetitia , Lablaine Armand , Pellegrini Olivier , Serrano Mónica , Tolcan Anastasia , Ventroux Magali , Durand Sylvain , Hamon Marion , Henriques Adriano O , Carballido-López Rut , Condon Ciarán
Published: January 2025

Faced with nutritional stress, some bacteria form endospores capable of enduring extreme conditions for long periods of time; yet the function of many proteins expressed during sporulation remains a mystery. We identify one such protein, KapD, as a 3′-exoribonuclease expressed under control of the mother cell-specific transcription factors SigE and SigK in Bacillus subtilis. KapD dynamically assembles over the spore surface through a direct interaction with the major crust protein CotY. KapD catalytic activity is essential for normal adhesiveness of spore surface layers. We identify the sigK mRNA as a key KapD substrate and and show that the stability of this transcript is regulated by CotY-mediated sequestration of KapD. SigK is tightly controlled through excision of a prophage-like element, transcriptional regulation and the removal of an inhibitory pro-sequence. Our findings uncover a fourth, post-transcriptional layer of control of sigK expression that couples late-stage gene expression in the mother cell to spore morphogenesis.
Nonlinear regulatory dynamics of bacterial restriction-modification systems modulates horizontal gene transfer susceptibility
Authors: Djordjevic Magdalena , Zivkovic Lidija , Ou Hong-Yu , Djordjevic Marko
Published: January 2025

Type II restriction-modification (R–M) systems play a pivotal role in bacterial defense against invading DNA, influencing the spread of pathogenic traits. These systems often involve coordinated expression of a regulatory protein (C) with restriction (R) enzymes, employing complex feedback loops for regulation. Recent studies highlight the crucial balance between R and M enzymes in controlling horizontal gene transfer (HGT). This manuscript introduces a mathematical model reflecting R–M system dynamics, informed by biophysical evidence, to minimize reliance on arbitrary parameters. Our analysis clarifies the observed variations in M-to-R ratios, emphasizing the regulatory role of the C protein. We analytically derived a stability diagram for C-regulated R–M systems, offering a more straightforward analysis method over traditional numerical approaches. Our findings reveal conditions leading to both monostability and bistability, linking changes in the M-to-R ratio to factors like cell division timing and plasmid replication rates. These variations may link adjusting defense against phage infection, or the acquisition of new genes such as antibiotic resistance determinants, to changing physiological conditions. We also performed stochastic simulations to show that system regulation may significantly increase M-to-R ratio variability, providing an additional mechanism to generate heterogeneity in bacterial population.
Modular organization of enhancer network provides transcriptional robustness in mammalian development
Authors: Lin Hongli , Ye Xinyun , Chen Wenyan , Hong Danni , Liu Lifang , Chen Feng , Sun Ning , Ye Keying , Hong Jizhou , Zhang Yalin , Lu Falong , Li Lei , Huang Jialiang
Published: January 2025

Enhancer clusters, pivotal in mammalian development and diseases, can organize as enhancer networks to control cell identity and disease genes; however, the underlying mechanism remains largely unexplored. Here, we introduce eNet 2.0, a comprehensive tool for enhancer networks analysis during development and diseases based on single-cell chromatin accessibility data. eNet 2.0 extends our previous work eNet 1.0 by adding network topology, comparison and dynamics analyses to its network construction function. We reveal modularly organized enhancer networks, where inter-module interactions synergistically affect gene expression. Moreover, network alterations correlate with abnormal and dynamic gene expression in disease and development. eNet 2.0 is robust across diverse datasets. To facilitate application, we introduce eNetDB (https://enetdb.huanglabxmu.com), an enhancer network database leveraging extensive scATAC-seq (single-cell assay for transposase-accessible chromatin sequencing) datasets from human and mouse tissues. Together, our work provides a powerful computational tool and reveals that modularly organized enhancer networks contribute to gene expression robustness in mammalian development and diseases.
Do salient climatic risks affect shareholder voting?
Authors: Fich Eliezer M , Xu Guosong
Published: January 2025

Institutional investors affected by hurricanes subsequently support environmental proposals in non-affected firms even if they never voted for similar initiatives. Affected investors raise their holdings in firms where their pro-environment votes are consequential. The increased voting support after hurricanes has real effects as environmental proposals endorsed by more hurricane-afflicted investors are more likely to pass. Moreover, both market capitalization and analysts’ recommendations decline after firms pass environmental proposals. Our evidence suggests that natural disasters raise institutional investors’ concerns about the environment and about potential fund flow disruptions. These concerns, in turn, influence environmental activism, corporate policies, and firm performance.
Psychiatric Gaslighting: The Surveillance of Mental Illness during Pregnancy
Authors: Abel Charlotte , Timmermans Stefan
Published: January 2025

Women living with mental health symptoms face the dilemma of continuing psychotropic medication when pregnant or breastfeeding. Based on two years of observations in a mental health clinic focusing on reproductive health, we examine how patients living with mental health conditions exert reproductive agency during meetings with psychiatrists; how these clinicians respond to this engagement; and the consequences of this advocacy for medical decision-making. We find that psychiatrists psychologize patient advocacy by interpreting it as a manifestation of untreated mental pathology. This psychologization moves beyond imposing a professional vision on the interaction and beyond a paternalistic communication style to psychiatric gaslighting: patient engagement is invalidated and subverted under psychiatric professional vision to double-down on psychotropic medication. Psychiatric gaslighting is a sociological and institutional phenomenon; operating through cultural scripts about how both gender and mental illness shape credibility, incentive structures in medical practice, lingering epistemic problems in psychiatry, and psychiatry’s struggle for professional legitimacy. Within an unequal power relationship between health professionals aiming to safeguard their authority and a stigmatized population, patients are disempowered by psychiatric concepts that link mental health to good mothering. We conclude that the biomedical management of vulnerable populations serves professional interests.
Spatiotemporal landscape of kidney in a mouse model of hyperuricemia at single‐cell level
Authors: Chang Haining , Tao Qianru , Wei Lan , Wang Yangyang , Tu Chao
Published: January 2025

Serum uric acid is an end‐product of purine metabolism. Uric acid concentrations in excess of the physiological range may lead to diseases such as gout, cardiovascular disease, and kidney injury. The kidney includes a variety of cell types with specialized functions such as fluid and electrolyte homeostasis, detoxification, and endocrine functions. Two‐thirds of uric acid is excreted through kidney, however, the exploration of markers and new therapeutic targets in renal tissue of hyperuricemia is still lacking. Single‐cell and spatial omics techniques represent major milestones in life sciences. The combined measurement of the physical structure and molecular characteristics of tissues facilitates the exploration of the pathophysiological processes underlying disease development and the discovery of possible therapeutic targets. Here, the spatiotemporal atlas of hyperuricemic nephropathy was investigated using single‐cell RNA sequencing, spatial transcriptomics, spatial proteomics, and spatial metabolomics in a urate oxidase knockout mouse model. Several emerging targets and pathways especially ribosome and metabolism related to uric acid excretion were discovered and will be investigated further in studies on lowering uric acid.
Pregnancy Outcomes After Transvaginal Radiofrequency Ablation of Leiomyomas
Authors: Rey Victoria E. , Falcon Maria M. , Ferrara Ida , Yanes Gabriel
Published: January 2025

OBJECTIVE:

To evaluate pregnancy outcomes after transvaginal radiofrequency ablation of leiomyomas.

METHODS:

We conducted a retrospective review of the medical records of 226 pregnant patients after transvaginal radiofrequency ablation of leiomyomas from January 1, 2017, to February 28, 2022.

RESULTS:

Patients' mean age was 37.4 years. The preoperative median leiomyoma volume before transvaginal radiofrequency ablation was 52.4 mL, and the median volume reduction at 6 and 12 months was 49.4% and 69.8%, respectively. The median interval time from transvaginal radiofrequency ablation to pregnancy was 9.3 months (interquartile range 5.6–15.1 months). Pregnancy was spontaneous in 78 patients (34.5%) and by assisted reproductive technologies in 148 (65.5%). Miscarriage occurred in 36 patients (15.9%), premature delivery (before 37 weeks of gestation) in 4.1%, and preeclampsia in 4.3%. There was one instance of placenta accreta in a patient with a history of open myomectomy. There were no instances of uterine rupture, placental abruption, or fetal growth restriction. The cesarean delivery rate was 26.4%; the remaining patients had normal spontaneous vaginal deliveries. Patients with a volume of leiomyoma more than 58.6 mL had a longer interval time from transvaginal radiofrequency ablation to pregnancy (P<.05). An increased miscarriage rate was observed when the interval time to pregnancy was shorter than 5.7 months (P<.05).

CONCLUSION:

Pregnancy outcomes after transvaginal radiofrequency ablation of leiomyomas were similar to those of a general population with no instances of uterine rupture, placental abruption, or fetal growth restriction.
The risks of pityriasis rosea in pregnancy: a review
Authors: Manduca Sophia , Oh Christina S. , Ong Michael , Lipner Shari R. , Pomeranz Miriam K. , Bieber Amy K.
Published: January 2025

Objective:

This review aims to consolidate available evidence, identify research gaps, and advocate for a more informed approach to the management of pityriasis rosea in pregnant individuals.

Data Sources:

PubMed, Web of Science, and Directory of Open Access Journals were systematically searched based on the keywords “pityriasis rosea,” “pityriasis circinate,” “roseola annulate,” “herpes tonsurans maculosus,” “herald patch,” and “pregnancy” on January 25, 2024 for publications between 1950 to 2024.

Study Selection:

Studies containing outcomes data for pregnant patients with established PR were included. Studies must have been written or translated into English and published in a peer-reviewed journal. Studies which did not pertain to PR in the setting of pregnancy were excluded, as screened by two reviewers. Responses, general informational reviews, and letters to the editor without novel data were also excluded.

Results:

Eleven relevant articles were identified, encompassing data from 177 patients. Overall, 81% of patients had favorable outcomes while 19% experienced unfavorable outcomes. PR onset before 15 weeks gestation was associated with a higher rate of unfavorable outcomes (41%), including a 27% rate of spontaneous abortion (SA). Conversely, PR onset after 15 weeks had a lower unfavorable outcome rate (21%), and no instances of SA.

Conclusion:

Conflicting data exists regarding the impact of PR on pregnancy outcomes. However, PR onset within the first 15 weeks, widespread lesions, constitutional symptoms, and higher human herpesvirus 6 viral loads may increase the risk of unfavorable outcomes such as SA. Close follow-up and consideration of antiviral treatment are recommended for high-risk patients.
The show must go on: a reliability assessment platform for resistive random access memory crossbars
Authors: Pelke Rebecca , Staudigl Felix , Thomas Niklas , Hossein Mohammed , Bosbach Nils , Cubero-Cascante José , Leupers Rainer , Joseph Jan Moritz
Published: January 2025

Resistive random access memory (ReRAM) holds promise for building computing-in-memory (CIM) architectures to execute machine learning (ML) applications. However, existing ReRAM technology faces challenges such as cell and cycle variability, read-disturb and limited endurance, necessitating improvements in devices, algorithms and applications. Understanding the behaviour of ReRAM technologies is crucial for advancement. Existing platforms can either only characterize single cells and do not support CIM operations, or lack a comprehensive software stack for simple system integration. This article introduces NeuroBreakoutBoard (NBB), a versatile, integrable and portable instrumentation platform for ReRAM crossbars. The platform features a software stack enabling experiments via Python from a host PC. In a case study, we demonstrate the capabilities of NBB by conducting diverse experiments on TiN/Ti/HfO
2
/TiN cells. Our results show that NBB can characterize individual cells and perform CIM operations with a relative measurement error below 2%.

This article is part of the theme issue ‘Emerging technologies for future secure computing platforms’.
Protected memristive implementations of cryptographic functions
Authors: Chen Ziang , Chen Li-Wei , Zhao Xianyue , Li Kefeng , Schmidt Heidemarie , Polian Ilia , Du Nan
Published: January 2025

Memristive technology mitigates the memory wall issue in von Neumann architectures by enabling in-memory data processing. Unlike traditional complementary metal-oxide semiconductor (CMOS) technology, memristors provide a new paradigm for implementing cryptographic functions and security considerations. While prior research explores memristors for cryptographic functions and side-channel attack vulnerabilities, our study uniquely addresses memristor-oriented countermeasures. We review different memristive crossbar configurations, implement a four-bit S-box cryptographic function, and analyse memristor-oriented hiding and masking techniques using a self-rectifying passive crossbar. Our findings confirm the efficacy of memristor-oriented hiding techniques but highlight limitations in memristor-oriented masked dual-rail pre-charge logic (MDPL) masking methods. Effective MDPL masking depends on specific power consumption conditions, i.e. the power profile of input data ‘01’ and ‘10’ are not clearly distinguishable from ‘00’ and ‘11’, which, however, are not satisfied across various memristive logic families. Despite passing
t
-tests, xor4Sbox with CRS-based MDPL masking failed stochastic approaches owing to power consumption differences. Our study prioritizes memristor-oriented countermeasures, advancing the understanding of challenges and opportunities in memristive technology for cryptographic functions.

This article is part of the theme issue ‘Emerging technologies for future secure computing platforms’.
In-memory encryption using the advanced encryption standard
Authors: Kovats Tobias , Rameshan Navaneeth , Karunaratne Kumudu Geethan , Giannopoulos Iason , Sebastian Abu
Published: January 2025

Encryption and decryption of data with very low latency and high energy efficiency is desirable in almost every application that deals with sensitive data. The advanced encryption standard (AES) is a widely adopted algorithm in symmetric key cryptography with numerous efficient implementations. Nonetheless, in scenarios involving extensive data processing, the primary limitations on performance and efficiency arise from data movement between memory and the processor, rather than data processing itself. In this article, we present a novel in-memory computing (IMC) approach for AES encryption and key-expansion, and experimentally validate it on an IMC prototype chip based on phase-change memory (PCM) technology. We leverage operators stored in PCM crossbar arrays to achieve the flexibility to tune performance at runtime based on the amount of free storage available in the memory system. In addition, we introduce a method for parallel in-memory polynomial modular multiplication and evaluate the potential of intrinsic stochastic properties of PCM devices for random key generation. We show how to further improve efficiency with minimal additional auxiliary circuitry. To evaluate the performance within a custom-built large-scale in-memory AES system, we design and implement a cycle-accurate simulator that integrates parameters from Spice simulations for detailed latency and energy consumption analysis of the AES algorithm. Our evaluations indicate that our IMC-based AES approach outperforms state-of-the-art methods, achieving speed factor improvements of up to 19.7 at equivalent energy efficiency.

This article is part of the theme issue ‘Emerging technologies for future secure computing platforms’.
Secure artificial intelligence at the edge
Authors: Sehatbakhsh Nader , Pamarti Sudhakar , Roychowdhary Vwani , Iyer Subramanian
Published: January 2025

Sensors for the perception of multimodal stimuli—ranging from the five senses humans possess and beyond—have reached an unprecedented level of sophistication and miniaturization, raising the prospect of making man-made large-scale complex systems that can rival nature a reality. Artificial intelligence (AI) at the edge aims to integrate such sensors with real-time cognitive abilities enabled by recent advances in AI. Such AI progress has only been achieved by using massive computing power which, however, would not be available in most distributed systems of interest. Nature has solved this problem by integrating computing, memory and sensing functionalities in the same hardware so that each part can learn its environment in real time and take local actions that lead to stable global functionalities. While this is a challenging task by itself, it would raise a new set of security challenges when implemented. As in nature, malicious agents can attack and commandeer the system to perform their own tasks. This article aims to define the types of systemic attacks that would emerge, and introduces a multiscale framework for combatting them. A primary thesis is that edge AI systems have to deal with unknown attack strategies that can only be countered in real time using low-touch adaptive learning systems.

This article is part of the theme issue ‘Emerging technologies for future secure computing platforms’.
Optical metabolic imaging identifies metabolic shifts and mitochondria heterogeneity in POLG mutator macrophages
Authors: Hu Linghao , West A. Phillip , Walsh Alex J.
Published: January 2025

The polymerase gamma (POLG) gene mutation is associated with mitochondria and metabolism disorders, resulting in heterogeneous responses to immunological activation and posing challenges for mitochondrial disease therapy. Optical metabolic imaging captures the autofluorescent signal of two coenzymes, NADH and FAD, and offers a label-free approach to detect cellular metabolic phenotypes, track mitochondria morphology, and quantify metabolic heterogeneity. In this study, fluorescence lifetime imaging (FLIM) of NAD(P)H and FAD revealed that POLG mutator macrophages exhibit a decreased NAD(P)H lifetime, and optical redox ratio compared to the wild-type macrophages, indicating an increased dependence on glycolysis. FLIM revealed that both wild-type and POLG mutator macrophages switch to a decreased NAD(P)Hτ1, andτmafter immune stimulation by Lipopolysaccharides (LPS). Furthermore, a bimodality index of subpopulation analysis identified heterogenous populations of POLG mutator macrophage responses under immune challenge by LPS. Moreover, to quantify the mitochondria variations in POLG mutator macrophages, a customized thresholding image processing pipeline was developed to segment mitochondria regions within each cell from the NADH image, allowing for the feature analysis of mitochondria clusters. Consequently, the wild-type macrophages exhibited a higher percentage of mitochondria-containing pixels and longer lengths of connected mitochondria, as compared with POLG mutated macrophages. Altogether, these results illustrate the potential of optical metabolic imaging for non-invasive detection and quantification of cellular metabolism, metabolic heterogeneity within cell populations, and intra-cellular mitochondria morphology differences in POLG mutator macrophages. Optical metabolic imaging will be valuable for studying POLG-mutation diseases and evaluating efficacy of potential therapies.
The membrane topology problem inherent in ciliogenesis is solved by ciliary recruitment of a phospholipid flippase
Authors: Wang Zhengmao , He Ruida , Liu Qingqing , Snell William J. , Cao Muqing , Pan Junmin
Published: January 2025

The cilium is a slender cellular projection whose membrane transduces signals essential in development and homeostasis. Although assembly of the axonemal core of the organelle is well-studied, the mechanisms that underlie formation of the ∼250 nm diameter ciliary membrane from oppositely curved 50-100 nm diameter pre-ciliary vesicles remain poorly understood. Here we report that during ciliogenesis in the bi-ciliated alga,Chlamydomonas reinhardtii, aminophospholipid flippase 2 (ALA2) is recruited laterally from a reservoir on the plasma membrane onto the nascent ciliary membrane where it transfers conically shaped phosphatidyl ethanolamine (PE) from the outer to the inner leaflet. In cells lacking ALA2, initiation of cilia regeneration after experimentally induced de-ciliation is delayed, PE flipping is impaired, the ciliary membrane becomes distorted, and cilia that do form are shorter than wild type. Our results uncover a membrane topology problem inherent in ciliogenesis and demonstrate that it is resolved by a phospholipid flippase.

Highlights

Membranes of pre-ciliary vesicles reverse curvature to become the ciliary membrane

Upon initiation of ciliogenesis, plasma membrane ALA2 transits laterally to cilia

The ciliary membranes ofala2mutants fail to conform to axonemal shape

ALA2 flips PE to establish ciliary membrane curvature
Leveraging High-Throughput Data to estimate Leukocyte Telomere Length in the Million Veteran Program
Authors: Iyer Kruthika R. , Vembu Prathima , Barad Alexa , Guarischi-Sousa Rodrigo , Sarro Joseph , Billing-Ross Paul , Assimes Themistocles L. , Clarke Shoa L. , Tcheandjieu Catherine , Huffman Jennifer E , Tsao Phil
Published: January 2025

Telomeres are highly repeated DNA sequences that stop chromosome ends from fraying. They shorten as we age, making them markers of biological aging. In this study, we employed an innovative approach to estimate leukocyte telomere length (LTL) through the utilization of the bioinformatics tool TelSeq, leveraging existing whole-genome sequencing data sourced from the Department of Veteran Affairs’ Million Veteran Program (MVP) encompassing a cohort of 102,646 diverse individuals.

Using the TelSeq-estimated LTL, we conducted parametric and non-parametric statistical analyses with demographic descriptors such as age, sex, and genetically inferred ancestry (GIA). Our results revealed a near-linear yet modest inverse correlation between age and LTL (ρ= −0.20, p < 1E-300). Specifically, each year increase in age corresponded to an 8bp LTL decrease (p < 1E-300) after adjusting for sex and GIA groups. Females had longer LTL than males, even after controlling for ancestry and age (β = 58 bp, p < 1E-300). Additionally, differences in LTL were observed among ancestry groups (Median LTLAfrican= 2.03kb, Median LTLEuropean= 2.01kb, Median LTLAdmixedAmerican= 2.00kb), however, these differences were not statistically significant between the two largest groups - African and European ancestry. To validate TelSeq-estimated LTL, we utilized methylation profiles of 140 cytosine-phosphate-guanine dinucleotides (CpGs) on 28,669 individuals to derive DNA methylation-based telomere length estimator (DNAmTL). DNAmTL had a modest correlation with TelSeq-estimated LTL (ρ=0.21, p < 1E-300). Consistent with Telseq-estimated LTL, DNAmTL was inversely associated with age where each year increase corresponded to 16bp DNAmTL decrease (p < 1E-300) after adjusting for sex and GIA groups. After controlling for these parameters, males were also found to exhibit shorter DNAmTL than females (β = −98 bp, p < 1E-300), similar to observations from TelSeq-estimated LTL. Lastly, individuals of African and Admixed-American ancestry had longer DNAmTL than those of European ancestry.

These findings align with existing literature elucidating the effects of age, sex, and ancestry on telomere length variations, and also represent the first comparison of TelSeq-derived LTL with methylation-derived DNAmTL. This valuable resource is now accessible to the broader MVP community, facilitating further telomere research.
Association of non-HDL-C and risk of incident hypertension
Authors: He Xinxin , Yin Lei , Zhao Yujie , Yang Bin , Zhao Yang , Fu Xueru , Wu Yuying , Wang Mengdi , Liu Mengna , Su Yijia , Ren Yongcheng , Liu Yu , Zhang Ming , Hu Dongsheng
Published: January 2025

Background

The study aimed to investigate the association between non-high-density lipoprotein cholesterol (non-HDL-C) and risk of incident hypertension, especially concerning the association of different levels of low-density lipoprotein cholesterol (LDL-C) and non-HDL-C with risk of incident hypertension.

Methods

A total of 10,623 participants from the Rural Chinese Cohort Study were included in the analyses. Non-HDL-C is the total cholesterol in the blood minus high-density lipoprotein cholesterol (HDL-C). The odds ratios (ORs) and 95% confidence intervals (95% CIs) between non-HDL-C, LDL-C, and risk of incident hypertension were estimated using logistic regression models.

Results

During the 10-year follow-up, 3,110 newly diagnosed hypertensive patients were identified. After adjustment for potential confounders, baseline non-HDL-C level was associated with higher risk of hypertension: the OR for the highest vs lowest quartile was 1.79 (95% CI: 1.43-2.24). For each standard deviation (SD) increase in non-HDL-C, risk of incident hypertension increased by 41%. When LDL-C was within the ideal level (<2.6 mmol/L) but non-HDL-C was above the ideal level (≥3.4 mmol/L), the risk of incident hypertension was elevated by 56% compared to when both of them were at ideal levels. Conversely, no such increased risk was observed when the LDL-C level was non-ideal while non-HDL-C remained within the ideal level.

Conclusions

Serum non-HDL-C level was found to be positively associated with the risk of incident hypertension in rural Chinese adults, an association independent of LDL-C, suggesting that further lowering of non-HDL-C by interventions to reduce residual risk of incident hypertension would be beneficial.
Metabolic Signatures of Immune Checkpoint Inhibitor Response in Gynecologic Cancers: Insights from Flux Balance Analysis
Authors: Idumah Gideon , Li Lin , Yehia Lamis , Mahdi Haider , Ni Ying
Published: January 2025

Modifiers of immune checkpoint inhibitor (ICI) responses in cancer patients are complex and remain poorly characterized, especially in gynecologic cancers. In this study, we explored fluxomic biomarkers that differentiate responders from non-responders to ICIs in a series of 49 patients with gynecologic cancers, including ovarian, cervical, and endometrial cancers. By applying metabolic enzyme expression as constraints, we utilized an objective-customizable flux balance analysis within a genome-scale metabolic model to predict the metabolic flux differences between responders versus non-responders of ICI treatment. We identified three reactions with consistent differential activity across all ten different optimization objectives: Succinate Dehydrogenase (SUCD1m) in the citric acid cycle, NADH: Guanosine-5-Phosphate Oxidoreductase (r0276) involved in purine catabolism, and Ornithine Transaminase Reversible, Mitochondrial (ORNTArm) in the urea cycle. Additionally, reactions within the folate cycle subsystem, particularly involving MTHFD2, demonstrated significance in distinguishing treatment responses, aligning with previous findings linking MTHFD2 to immune evasion and tumor progression. To further analyze the association between metabolic features and survival outcomes, we implemented machine learning models that integrate multi-omics data. Our model included clinical-pathologic, molecular-genomic features (gene expression, TGF-β score, immune cell abundance from transcriptomic deconvolution), and significant reaction fluxes. Our findings suggest that SUCD1m, MTHFDm and ORNTArm are important metabolic biomarkers that could serve as predictive indicators for ICI response and, if validated in a larger cohort, may guide the development of targeted therapies to enhance treatment efficacy for gynecologic cancer patients. This study highlights the use of genome-scale metabolic modeling to identify clinically relevant biomarkers and improve therapeutic strategies.
miR-29a-3p and TGF-β Axis in Fanconi Anemia: Mechanisms Driving Metabolic Dysfunction and Genome Stability
Authors: Bertola Nadia , Regis Stefano , Cossu Vanessa , Balbi Matilde , Serra Martina , Corsolini Fabio , Bottino Cristina , Degan Paolo , Dufour Carlo , Pierri Filomena , Cappelli Enrico , Ravera Silvia
Published: January 2025

Fanconi anemia (FA) is a rare genetic disorder characterized by bone marrow failure and cancer susceptibility due to defective DNA double-strand break repair. However, FA cells are also characterized by mitochondrial dysfunction and redox imbalance. To identify a common factor among these alterations, we focused on miR-29a-3p, a microRNA involved in hematopoiesis. Our data show that miR-29a-3p is downregulated in lymphoblasts and fibroblasts mutated for the FANC-A gene, causing the overexpression of its target genes, FOXO3, SGK1, and IGF1, which results in PI3K/AKT pathway hyperactivation, altered mitochondrial metabolism and insufficient antioxidant response. Furthermore, miR-29a-3p downregulation appears associated with hyperactivation of the TGF-β signal. However, restoring miR-29a-3p expression improves mitochondrial metabolism, oxidative stress response, and DNA damage repair by inhibiting the PI3K/AKT pathway and modulating TGF-β signaling by a feedback mechanism. Based on these findings, miR-29a-3p appears as a promising molecular target to address several mechanisms based on FA pathogenesis.