bluuebunny/crossref_metadata_2025 huggingface dataset:
A multicriteria decision-making model for the selection of conventional/hybrid coagulants in water treatment
Authors: Ozgur Cihan , Gurhan Abdi Bozkurt , Kaplan Bekaroglu Sehnaz Sule
Published: January 2025

The coagulation process is a well-known process that has been used in water treatment for many years. The coagulation process shows treatment efficiency in terms of turbidity and suspended solids removal. However, despite good results, coagulant selection is not an easy task. A coagulant can effectively remove suspended solids but, at the same time, increase conductivity; coagulants can also significantly increase chemical sludge production. The final selection of coagulants depends on the importance attributed to the parameter desired to be removed. In this study, the use of multicriteria decision-making is proposed to help select organic coagulants and hybrid coagulants, which have emerged as an alternative to inorganic coagulants in recent years due to the disadvantages of chemical coagulants and whose use and variety are increasing. Therefore, starting from the parameters determined by coagulation process results, these techniques allow weighting these parameters according to the judgments of drinking water treatment plant professionals and determining priorities among coagulants. The agreement between the obtained results and the literature shows that the analytical hierarchy process (AHP) method is a useful tool for selecting coagulants. According to the results of the AHP matrix created with four criteria and nine alternatives, it was found that hybrid coagulants with similar performance to inorganic coagulants have not yet been adopted by drinking water treatment professionals. This may have been due to the higher price of hybrid coagulants and the fact that they are not yet widely used in the drinking water industry.
Country of origin and prices of systemic antibiotics in Vietnam: a multicentre retrospective study
Authors: Dat Vu Quoc
Published: January 2025

Background

Local production of antibiotics is essential for improving access to treatment of clinical infection and avoiding vulnerability to expensive drug imports.

Objectives

To describe the country of origin and cost of antibiotics in Vietnam.

Methods

This was an observational study. Antibiotic procurement in 372 healthcare facilities in Vietnam between 2018 and 2022 were included in this analysis. Antibiotics were classified using the Anatomical Therapeutic Chemical Index and the 2021 WHO Access, Watch and Reserve groups. The country of origin of antibiotics was determined by the place where the final products were manufactured. Antibiotic costs were estimated in US dollars per DDD and adjusted by annual inflation.

Results

This study included 2.54 billion antibiotic DDDs, totalling 3.13 billion US dollars. Local production accounted for 80.2% of the number of DDDs and 43.4% of the total expenditure. The antibiotics from other countries were driven by imports from high-income countries, which accounted for 75.5% of DDDs and 89.6% of the expenditure on imported antibiotics. Availability of Reserve group antibiotics was more dependent on imports from high-income countries (36.6% of DDDs) than those of Access (15.7% of DDDs) and Watch group antibiotics (14.2% of DDDs).

Conclusions

A comprehensive policy approach is needed to ensure the affordability and to reduce dependency on imported Reserve group antibiotics.
Safety, Tolerability, and Pharmacokinetics of Long-Acting Broadly Neutralizing HIV-1 Monoclonal Antibody VRC07–523LS in Newborn Infants Exposed to HIV-1
Authors: Cunningham Coleen K , McFarland Elizabeth J , Muresan Petronella , Capparelli Edmund V , Perlowski Charlotte , Johnston Benjamin , Bone Frederic , Purdue Lynette , Yin Dwight E , Moye Jack , Spiegel Hans M L , Majji Sai , Theron Gerhard B , Mujuru Hilda A , Purswani Murli , Alvarez Grace , Deville Jaime G , Chambers Carrie , Brown Emily , Harding Paul A , Tobin Nicole H , Low Kwang , Gama Lucio
Published: January 2025

Background

Vertical HIV-1 transmission despite antiretroviral therapy may be mitigated by the use of long-acting, broadly neutralizing, monoclonal antibodies (bNAb) such as VRC07–523LS. The present study was designed to determine the safety and pharmacokinetics of VRC07–523LS.

Methods

VRC07–523LS, 80 mg/dose, was administered subcutaneously after birth to non-breastfed (cohort 1; N = 11, enrolled in USA) and breastfed (cohort 2; N = 11, enrolled in South Africa and Zimbabwe) infants exposed to HIV-1. Breastfed infants (cohort 2) received a second 100-mg dose at 12 weeks if still receiving breastmilk. All infants received antiretroviral prophylaxis in addition to VRC07–523LS. VRC07–523LS levels were compared to VRC01 levels, as determined previously in this study.

Results

Local reactions (all grade ≤ 2) occurred after dose 1 in 18% of infants in cohort 1 and after doses 1 and 2 in 100% of infants in cohort 2. The VRC07–523LS dose at birth (mean 26 mg/kg) achieved a mean ± SD plasma level of 222.3 ± 71.6 mcg/mL by 24 hours and 18.4 ± 7.2 mcg/mL at week 12, prior to dose 2. The pre-established target of ≥ 10 mcg/mL at week 12 was met in 94% of infants. The terminal half-life of VRC07–523LS was observed to be 39.2 ± 5.0 days. At week 4 and week 8, bNAb levels were significantly higher (P ≤ .002) after one dose of VRC07–523LS, compared to one dose of VRC01 (20 mg/kg). No infant included in the study acquired HIV-1.

Conclusions

VRC07–523LS was well tolerated with pharmacokinetics that support further studies of potent long-acting bNAbs together with antiretrovirals to prevent HIV-1 acquisition in infants.
Misidentification of short GRBs as magnetars in nearby galaxies
Authors: Schösser Elisa C , Burgess J Michael , Greiner Jochen
Published: January 2025

GRB 200415A, a short and very bright pulse of $\gamma$-rays, has been claimed to be an extragalactic magnetar giant flare (MGF) in the galaxy ${\mathrm{NGC}\, 253}$. However, as the redshift of the transient was not measured, it is possible that the measured location of the transient on the celestial sphere and the location of the local galaxy merely coincided. Thus, its real progenitor could have been arbitrarily far away, leading to a much larger luminosity of the transient, and leaving the standard model of short gamma-ray bursts (sGRBs), the merger of two compact objects, as an explanation for the observations. Prior to that event, three other sGRBs were proposed to be extragalactic MGFs, which, however, had a substantially wider localization error box. A very recent example is GRB 231115A with its error circle projecting on to M82. We compute the probability for the misinterpretation of sGRBs as extragalactic MGFs by simulating synthetic surveys of sGRB observations. Applying five criteria – incorporating factors such as host galaxy star formation rate, gamma-ray burst monitor trigger, GRB duration, isotropic energy release, and fluence – we identify candidates within the simulated surveys that mimic MGF characteristics. In a non-negligible fraction, 12.5 per cent, of the simulated surveys, we identify at least one sGRB with same characteristics as an MGF. Thus, we conclude that the selection criteria proposed in previous works for the identification of extragalactic MGFs, are not sufficient to reject the sGRB hypothesis. However, our analysis cannot prove that a specific one of the previously proposed extragalactic MGFs is an sGRB.
The VMC Survey – LI. Classifying extragalactic sources using a probabilistic random forest supervised machine learning algorithm
Authors: Pennock Clara M , van Loon Jacco Th , Cioni Maria-Rosa L , Maitra Chandreyee , Oliveira Joana M , Craig Jessica E M , Ivanov Valentin D , Aird James , Anih Joy O , Cross Nicholas J G , Dresbach Francesca , de Grijs Richard , Groenewegen Martin A T
Published: January 2025

We used a supervised machine learning algorithm (probabilistic random forest) to classify ∼130 million sources in the VISTA Survey of the Magellanic Clouds (VMC). We used multi-wavelength photometry from optical to far-infrared as features to be trained on, and spectra of Active Galactic Nuclei (AGN), galaxies and a range of stellar classes including from new observations with the Southern African Large Telescope (SALT) and SAAO 1.9m telescope. We also retain a label for sources that remain unknown. This yielded average classifier accuracies of ∼79% (SMC) and ∼87% (LMC). Restricting to the 56,696,719 sources with class probabilities (Pclass) > 80% yields accuracies of ∼90% (SMC) and ∼98% (LMC). After removing sources classed as ‘Unknown’, we classify a total of 707,939 (SMC) and 397,899 (LMC) sources, including >77,600 extragalactic sources behind the Magellanic Clouds. The extragalactic sources are distributed evenly across the field, whereas the Magellanic sources concentrate at the centres of the Clouds, and both concentrate in optical/IR colour–colour/magnitude diagrams as expected. We also test these classifications using independent datasets, finding that, as expected, the majority of X-ray sources are classified as AGN (554/883) and the majority of radio sources are classed as AGN (1756/2694) or galaxies (659/2694), where the relative AGN–galaxy proportions vary substantially with radio flux density. We have found: >49,500 hitherto unknown AGN candidates, likely including more AGN dust dominated sources which are in a critical phase of their evolution; >26,500 new galaxy candidates and >2800 new Young Stellar Object (YSO) candidates.
Distinct structural and functional heterochromatin partitioning of lamin B1 and lamin B2 revealed using genome-wide nicking enzyme epitope targeted DNA sequencing
Authors: Sen Sagnik , Estève Pierre-Olivier , Raman Karthikeyan , Beaulieu Julie , Chin Hang Gyeong , Feehery George R , Vishnu Udayakumar S , Xu Shuang-yong , Samuelson James C , Pradhan Sriharsa
Published: January 2025

Gene expression is regulated by chromatin DNA methylation and other features, including histone post-translational modifications (PTMs), chromatin remodelers and transcription factor occupancy. A complete understanding of gene regulation will require the mapping of these chromatin features in small cell number samples. Here we describe a novel genome-wide chromatin profiling technology, named as Nicking Enzyme Epitope targeted DNA sequencing (NEED-seq). NEED-seq offers antibody-targeted controlled nicking by Nt.CviPII-pGL fusion to study specific protein–DNA complexes in formaldehyde fixed cells, allowing for both visual and genomic resolution of epitope bound chromatin. When applied to nuclei, NEED-seq yielded genome-wide profile of chromatin-associated proteins and histone PTMs. Additionally, NEED-seq of lamin B1 and B2 demonstrated their association with heterochromatin. Lamin B1- and B2-associated domains (LAD) segregated to three different states, and states with stronger LAD correlated with heterochromatic marks. Hi-C analysis displayed A and B compartment with equal lamin B1 and B2 distribution, although methylated DNA remained high in B compartment. LAD clustering with Hi-C resulted in subcompartments, with lamin B1 and B2 partitioning to facultative and constitutive heterochromatin, respectively, and were associated with neuronal development. Thus, lamin B1 and B2 show structural and functional partitioning in mammalian nucleus.
Efficacy of fungicide treatments for the management of grape powdery mildew in Washington, 2024
Authors: Moyer Michelle Marie , Mireles Maria
Published: January 2025

Grape powdery mildew, caused by Erysiphe necator, is one of the most common diseases affecting wine grape production globally. Symptoms include white, powdery growth over all green surfaces of the plant, including foliage, fruit, shoots and tendrils. When infections are severe, photosynthesis is inhibited, fruit set can be reduced, and remaining berries can split. This report evaluates the efficacy of different fungicide regimes for their ability to control foliar and fruit powdery mildew on Vitis vinifera 'Chardonnay' in Prosser, WA in 2024. Results from this trial can be used to better time, and align, fungicides for improved disease control in wine grapes.
Investigation of a Novel Noninvasive Risk Analytics Algorithm With Laboratory Central Venous Oxygen Saturation Measurements in Critically Ill Pediatric Patients
Authors: Teele Sarah A. , Gazit Avihu Z. , Futterman Craig , La Cava William G. , Cooper David S. , Schwartz Steven M. , Salvin Joshua W.
Published: January 2025

BACKGROUND:

Accurate assessment of oxygen delivery relative to oxygen demand is crucial in the care of a critically ill patient. The central venous oxygen saturation (Svo
2) enables an estimate of cardiac output yet obtaining these clinical data requires invasive procedures and repeated blood sampling. Interpretation remains subjective and vulnerable to error. Recognition of patient’s evolving clinical status as well as the impact of therapeutic interventions may be delayed.

OBJECTIVE:

The predictive analytics algorithm, inadequate delivery of oxygen (IDo
2) index, was developed to noninvasively estimate the probability of a patient’s Svo
2 to fall below a preselected threshold.

DERIVATION COHORT:

A retrospective multicenter cohort study was conducted using data temporally independent from the design and development phase of the IDo
2 index.

VALIDATION COHORT:

A total of 20,424 Svo
2 measurements from 3,018 critically ill neonates, infants, and children were retrospectively analyzed. Collected data included vital signs, ventilator data, laboratory data, and demographics.

PREDICTION MODEL:

The ability of the IDo
2 index to predict Svo
2 below a preselected threshold (30%, 40%, or 50%) was evaluated for discriminatory power, range utilization, and robustness.

RESULTS:

Area under the receiver operating characteristic curve (AUC) was calculated for each index threshold. Datasets with greater amounts of available data had larger AUC scores. This was observed across each configuration. For the majority of thresholds, Svo
2 values were observed to be significantly lower as the IDo
2 index increased.

CONCLUSIONS:

The IDo
2 index may inform decision-making in pediatric cardiac critical care settings by providing a continuous, noninvasive assessment of oxygen delivery relative to oxygen demand in a specific patient. Leveraging predictive analytics to guide timely patient care, including support for escalation or de-escalation of treatments, may improve care delivery for patients and clinicians.
An Unusual Case of Medial Canthal Angioleiomyoma
Authors: Kothari Anoushka N. , Wang Delia D. , Menon Vivek A. , Sullivan Timothy J.
Published: January 2025

An 84-year-old Caucasian male was referred for evaluation of a worsening left medial canthal lesion for consideration of excision. The patient reported a 4-year history of the painless canthal lesion gradually increasing in size with progressively obstructed peripheral vision. On examination, the cream-colored cyst measured 10 × 8 mm. The best-corrected visual acuity with glasses was 6/7.5-2 in the right eye and 6/7.5 in the left eye with intraocular pressure of 10 mm Hg bilaterally. The lesion was excised under local anesthetic. Histopathology confirmed a cutaneous angioleiomyoma with adipocytic metaplasia. The postoperative course was uneventful, with a planned 3-month review for surveillance of recurrence.
Compound heterozygous mutations (p.L68R∗37 and p.T241N) lead to abnormal protein levels and structures in hereditary FVII deficiency
Authors: Luo Bingqing , Wu Xia , Zhu Jing , Chen Shu , Lou Shifeng , Tan Xiaoyan
Published: January 2025

Background

Congenital factor VII (FVII) deficiency is a genetic disorder characterized by decreased FVII activity, which sometimes leads to fatal bleeding. Numerous variants have been found in FVII deficiency, but mutations vary among patients. Each mutation deserves further exploration for each patient at risk of bleeding. We previously reported a Chinese patient with p.L68R∗37 and p.T241N compound heterozygous mutations. In this study, we further investigated the impact of these two mutations on the FVII expression through in vitro expression experiments.

Methods

Mutations were introduced into the FVII coding region using site-directed mutagenesis, and recombinant FVII was combined with two different plasmids, and then quantitative PCR and western blot analyses were performed subsequently.

Results

The p.L68R∗37 mutation had no effect on mRNA levels but caused a significant decrease in protein levels. In the p.T241N mutant vector, mRNA levels did not show a noticeable decrease, but protein levels exhibited a slight decrease. Structural analysis revealed that the p.T241N mutation resulted in an altered secondary structure and protein instability, indicating impaired functional properties.

Conclusion

Our study demonstrated that the p.L68R∗37 and p.T241N mutations impacted the protein levels and function of FVII, ultimately leading to a severe reduction in FVII activity. This study may contribute to further understanding of the molecular pathogenesis of FVII deficiency and offer insights for genetic counseling.
Hospital Artificial Intelligence/Machine Learning Adoption by Neighborhood Deprivation
Authors: Chen Jie , Yan Alice Shijia
Published: January 2025

Objective:

To understand the variation in artificial intelligence/machine learning (AI/ML) adoption across different hospital characteristics and explore how AI/ML is utilized, particularly in relation to neighborhood deprivation.

Background:

AI/ML-assisted care coordination has the potential to reduce health disparities, but there is a lack of empirical evidence on AI’s impact on health equity.

Methods:

We used linked datasets from the 2022 American Hospital Association Annual Survey and the 2023 American Hospital Association Information Technology Supplement. The data were further linked to the 2022 Area Deprivation Index (ADI) for each hospital’s service area. State fixed-effect regressions were employed. A decomposition model was also used to quantify predictors of AI/ML implementation, comparing hospitals in higher versus lower ADI areas.

Results:

Hospitals serving the most vulnerable areas (ADI Q4) were significantly less likely to apply ML or other predictive models (coef = −0.10, P = 0.01) and provided fewer AI/ML-related workforce applications (coef = -0.40, P = 0.01), compared with those in the least vulnerable areas. Decomposition results showed that our model specifications explained 79% of the variation in AI/ML adoption between hospitals in ADI Q4 versus ADI Q1–Q3. In addition, Accountable Care Organization affiliation accounted for 12%–25% of differences in AI/ML utilization across various measures.

Conclusions:

The underuse of AI/ML in economically disadvantaged and rural areas, particularly in workforce management and electronic health record implementation, suggests that these communities may not fully benefit from advancements in AI-enabled health care. Our results further indicate that value-based payment models could be strategically used to support AI integration.
Pediatric Health Assessment Tracker: A Quality Improvement Initiative to Obtain Weights Consistently and Appropriately in a Tertiary Pediatric Intensive Care Unit
Authors: Marron Alonso , Totapally Abhinav , Weatherly Allison , De Subhendu , Barber Madeline , Lifsey Allyson , Boyle Katharine
Published: January 2025

Introduction:

Weight is vital for tracking fluid status and nutrition and assuring patients have accurate dosing weights in the pediatric intensive care unit (PICU). Challenges in acquiring weights in critically ill patients include clinical instability, limited equipment, and lack of appropriate orders in the electronic medical record (EMR).

Methods:

We implemented interventions that targeted EMR weight orders and actual collection of weights in the 42-bed PICU of a children’s hospital. Preintervention data were collected from February to March 2023 for all patients admitted to the PICU with a length of stay (LOS) ≥3 days. We surveyed PICU nurses to identify barriers to collecting weights. Interventions included a multidisciplinary team approach, safety checklist, nursing education, and automatization of weight orders. The study team monitored the number of patients with weight orders and weights obtained as ordered twice weekly from March 2023 to April 2024 using statistical process control charts.

Results:

There were 1728 patient instances of LOS ≥3 days. Preintervention data showed 70.4% of patients with appropriate weight orders and 35.5% with weights obtained. Implementing a safety checklist, nursing education, EMR changes, and automatizing weight orders, the centerline for weight orders shifted to 94.3% and for weights obtained to 69.5%. Reminder emails to all ICU providers and nursing check-ins maintained the centerline. No increase in unplanned extubations occurred.

Conclusions:

Through interventions involving rounding providers, nurses, and the EMR, the frequency of weights ordered and obtained in a busy PICU sustainably increased.
Brain RNA profiling highlights multiple disease pathways in persons with HAND: uncovering determinants of biotype diversity
Authors: Branton William G. , Zhang Na , Cohen Eric A. , Brew Bruce J. , Gill M. John , Gelman Benjamin B. , Kong Linglong , Power Christopher
Published: January 2025

Objective:

To discover microRNA (miRNA)-RNA transcript interactions dysregulated in brains from persons with HIV-associated neurocognitive disorder (HAND), we investigated RNA expression using machine learning tools.

Design:

Brain-derived host RNA transcript and miRNA expression was examined from persons with or without HAND using bioinformatics platforms.

Methods:

By combining next generation sequencing, droplet digital (dd)PCR quantitation of HIV-1 genomes, with bioinformatics and statistical tools, we investigated differential RNA expression in frontal cortex from persons without HIV (HIV[-]), with HIV without brain disease (HIV[+]), with HIV-associated neurocognitive disorder (HAND), or HAND with encephalitis (HIVE).

Results:

Expression levels for 147 transcripts and 43 miRNAs showed a minimum 4-fold difference between clinical groups with a predominance of antiviral (Type I interferon) signaling-, neural cell maintenance-, and neurodevelopmental disorder-related genes that was validated by gene ontology and molecular pathway inferences. Scale of signal-to-noise ratio (SSNR) and biweight midcorrelation (bicor) analyses identified 14 miRNAs and 45 RNA transcripts, which were highly correlated and differentially expressed (p ≤ 0.05). Machine learning applications compared regression models predicated on HIV-1 DNA, or RNA viral quantities that disclosed miR-4683 and miR-154-5p were dominant variables associated with differential expression of host RNAs. These miRNAs were also associated with antiviral-, cell maintenance-, and neurodevelopmental disorder-related genes.

Conclusions:

Antiviral as well as neurodevelopmental disorder-related pathways in brain were associated with HAND, based on correlated RNA transcripts and miRNAs. Integrated molecular methods with machine learning offer insights into disease mechanisms, underpinning brain-related biotypes among persons with HIV that could direct clinical care.
Analysis of HIV transmission characteristics and intervention effects in Guangxi based on molecular networks
Authors: Pang Xianwu , Ma Jie , He Qin , Tang Kailing , Huang Jinghua , Fang Ningye , Xie Haoming , Lan Guanghua , Liang Shujia
Published: January 2025

Objective:

This study evaluates changes in HIV transmission and the effectiveness of interventions after two rounds of the Guangxi AIDS Conquering Project (GACP) in Guangxi, China.

Methods:

Samples and epidemiological data from newly diagnosed people living with HIV (PLWH) between 2014-2020 were analyzed. Molecular networks were constructed using nested PCR amplification and sequencing of the pol region, and multivariable logistic regression identified factors associated with clustering and high-degree nodes.

Results:

A total of 4,227 valid sequences (73.12% inclusion rate) were analyzed. Demographic changes included an increasing proportion of individuals aged ≥50 years (49.66%), with lower education (50.51%), peasants (76.82%), and heterosexual transmission (90.29%). The overall clustering rate was 86.89%, with higher clustering among individuals aged ≥50 (92.57%), those with primary school or below (89.09%), peasants (88.11%), and CRF08_BC infections (91.48%). Annual declines in cluster growth rate and clustering rates were observed, particularly among individuals aged <30, college graduates, men who have sex with men (MSM), and people who inject drugs (PWID). Key transmission hotspots were identified in Lingshan, particularly among older, less-educated individuals, and peasants. Factors associated with clustering included being male (aOR: 1.27), aged ≥50 (aOR: 3.84), and infected with CRF08_BC (aOR: 2.12). From 2017 to 2020, the risk of clustering and high-degree nodes was lower compared to 2014–2016, suggesting the effectiveness of interventions.

Conclusion:

Interventions in Guangxi effectively reduced HIV transmission among younger, high-degree populations. However, older, less-educated individuals remain at high risk, necessitating targeted strategies to address their specific needs and achieve better HIV control.
Automated polynomial formal verification using generalized binary decision diagram patterns
Authors: Schnieber Martha , Drechsler Rolf
Published: January 2025

With the ongoing digitization, digital circuits have become increasingly present in everyday life. However, as circuits can be faulty, their verification poses a challenging but essential challenge. In contrast to formal verification techniques, simulation techniques fail to fully guarantee the correctness of a circuit. However, due to the exponential complexity of the verification problem, formal verification can fail due to time or space constraints. To overcome this challenge, recently
Polynomial Formal Verification
(PFV) has been introduced. Here, it has been shown that several circuits and circuit classes can be formally verified in polynomial time and space. In general, these proofs have to be conducted manually, requiring a lot of time. However, in recent research, a method for automated PFV has been proposed, where a proof engine automatically generates human-readable proofs that show the polynomial size of a
Binary Decision Diagram
(BDD) for a given function. The engine analyses the BDD and finds a pattern, which is then proven by induction. In this article, we formalize the previously presented BDD patterns and propose algorithms for the pattern detection, establishing new possibilities for the automated proof generation for more complex functions. Furthermore, we show an exemplary proof that can be generated using the presented methods.

This article is part of the theme issue ‘Emerging technologies for future secure computing platforms’.
A comprehensive study of quantum arithmetic circuits
Authors: Wang Siyi , Li Xiufan , Lee Wei Jie Bryan , Deb Suman , Lim Eugene , Chattopadhyay Anupam
Published: January 2025

In recent decades, the field of quantum computing has experienced remarkable progress. This progress is marked by the superior performance of many quantum algorithms compared with their classical counterparts, with Shor’s algorithm serving as a prominent illustration. Quantum arithmetic circuits, which are the fundamental building blocks in numerous quantum algorithms, have attracted much attention. Despite extensive exploration of various designs in the existing literature, researchers remain keen to develop novel designs and improve existing ones. In this review article, we aim to provide a systematically organized and easily comprehensible overview of the current state of the art in quantum arithmetic circuits. Specifically, this study covers fundamental operations such as addition, subtraction, multiplication, division and modular exponentiation. We delve into the detailed quantum implementations of these prominent designs and evaluate their efficiency considering various objectives. We also discuss potential applications of the presented arithmetic circuits and suggest future research directions.

This article is part of the theme issue ‘Emerging technologies for future secure computing platforms’.
AxLaM: energy-efficient accelerator design for language models for edge computing
Authors: Glint Tom , Mittal Bhumika , Sharma Santripta , Ronak Abdul Qadir , Goud Abhinav , Kasture Neerja , Momin Zaqi , Krishna Aravind , Mekie Joycee
Published: January 2025

Modern language models such as bidirectional encoder representations from transformers have revolutionized natural language processing (NLP) tasks but are computationally intensive, limiting their deployment on edge devices. This paper presents an energy-efficient accelerator design tailored for encoder-based language models, enabling their integration into mobile and edge computing environments. A data-flow-aware hardware accelerator design for language models inspired by Simba, makes use of approximate fixed-point POSIT-based multipliers and uses high bandwidth memory (HBM) in achieving significant improvements in computational efficiency, power consumption, area and latency compared to the hardware-realized scalable accelerator Simba. Compared to Simba, AxLaM achieves a ninefold energy reduction, 58% area reduction and 1.2 times improved latency, making it suitable for deployment in edge devices. The energy efficiency of AxLaN is 1.8 TOPS/W, 65% higher than FACT, which requires pre-processing of the language model before implementing it on the hardware.

This article is part of the theme issue ‘Emerging technologies for future secure computing platforms’.
An Interpretable Sparse Graph Contrastive Learning Approach for Identifying Breast Cancer Risk Variants
Authors: Naga Raju Gudhe , Hartikainen Jaana M. , Tengström Maria , Pylkäs Katri , Winqvist Robert , Kosma Veli-Matti , Behravan Hamid , Mannermaa Arto
Published: January 2025

Genome-wide association studies (GWASs) have identified over 2,400 genetic variants associated to breast cancer. Conventional GWASs methods that analyze variants independently often overlook the complex genetic interactions underlying disease susceptibility. Machine and deep learning approaches present promising alternatives, yet encounter challenges, including overfitting due to high dimensionality (∼10 million variants) and limited sample sizes, as well as limited interpretability. Here, we present GenoGraph, a graph-based contrastive learning framework designed to address these limitations by modeling high-dimensional genetic data in low-sample-size scenarios. We demonstrate GenoGraph’s efficacy in breast cancer case-control classification task, achieving accuracy of 0.96 using the Biobank of Eastern Finland dataset. GenoGraph identified rs11672773 (ZNF8) as a key risk variant in Finnish population, with significant interactions with rs10759243 (KLF4) and rs3803662 (TOX3). Furthermore, in silico validation confirmed the biological relevance of these findings, underscoring GenoGraph’s potential to advance breast cancer risk prediction and elucidate genetic interactions for personalized medicine.
From macro to micro: De novo genomes of Aedes mosquitoes enable comparative genomics among close and distant relatives
Authors: Morinaga Gen , Balcazar Darío , Badolo Athanase , Iyaloo Diana , Tantely Luciano , Mouillaud Theo , Sharakhova Maria , Geib Scott M. , Paupy Christophe , Ayala Diego , Powell Jeffrey R. , Gloria-Soria Andrea , Soghigian John
Published: January 2025

The yellow fever mosquito (Aedes aegypti) is an organism of high medical importance because it is the primary vector for diseases such as yellow fever, Zika, dengue, and chikungunya. Its medical importance has made it a subject of numerous efforts to understand their biology. One such effort, was the development of a high-quality reference genome (AaegL5). However, this reference genome was sourced from a highly inbred laboratory strain with unknown geographic origin. Thus, the reference is not representative of a wild mosquito, let alone one from its native range in sub-Saharan Africa. To better understand the genetic architecture ofAe. aegyptiand their sister species, we developed twode novochromosome-scale genomes with sequences sourced from single individuals: one ofAe. aegypti formosus(Aaf) from Burkina Faso and one ofAe. mascarensis(Am) from Mauritius. Both genomes exhibit high contiguity and gene completeness, comparable to AaegL5. While Aaf exhibits high degree of synteny to AaegL5, it also exhibits several large inversions. We further conducted comparative genomic analyses using our genomes and other publicly available culicid reference genomes to find extensive chromosomal rearrangements between major lineages. Overrepresentation analysis of expanded genes in Aaf, AaegL5, and Am revealed that while the overarching category of genes that have expanded are similar, the specific genes that have expanded differ. Our findings elucidate novel insights into chromosome evolution at both microevolutionary and macroevolutionary scales. The genomic resources we present are additions to the arsenal of biologists in understanding mosquito biology and genome evolution.

Significance

Aedes aegyptiis a major arboviral disease vector found throughout the tropics and sub-tropics. Its subspecies differ ecologically, as native sub-Saharan African form feeds on mammals generally and inhabit both sylvatic and domestic areas and the global invasive form preferentially feeds on humans and lives primarily domestic areas. Their medical importance has prompted the development of a high-quality reference genome, but it was sourced from an inbred laboratory strain of unknown origin. Here, we leveraged PacBio HiFi sequencing and HiC sequencing to develop the first de novo genome ofAe. aegyptisampled its native range in Burkina Faso. We also present a de novo genome ofAe. mascarensis, its sister species. Our genomes are comparably contiguous and complete to the reference genome. Comparative genomic analysis using our genomes and other culicid reference genomes reveal extensive chromosomal rearrangements.
Assessment and staging of A/T/N with a single dynamic [18F]PI-2620 recording
Authors: Gnörich Johannes , Kusche-Palenga Julia , Kling Agnes , Dehsarvi Amir , Bronte Angela , Frontzkowski Lukas , Zatcepin Artem , Zaganjori Mirlind , Schöberl Florian , Roemer Sebastian N , Rauchmann Boris-Stephan , Kurz Carolin , Palleis Carla , Bernhardt Alexander M , Jäck Alexander , Katzdobler Sabrina , Scheifele Maximilian , Bauer Theresa , Bischof Gérard N , Eimeren Thilo van , Drzezga Alexander , Häckert Jan , Perneczky Robert , Rullmann Michael , Bürger Katharina , Zwergal Andreas , Levin Johannes , Bartenstein Peter , Sabri Osama , Barthel Henryk , Stöcklein Sophia , Höglinger Günter , Franzmeier Nicolai , Brendel Matthias
Published: January 2025

Patients with Alzheimer’s disease (AD) and clinically overlapping neurodegenerative diseases are classified molecularly using the A/T/N classification system. Apart from fluid biomarkers and structural MRI, the three-dimensional A/T/N system incorporates characteristic features from β-amyloid-PET (A), tau-PET (T), and FDG-PET (N). We evaluated if dynamic features of tau-PET with [18F]PI-2620 allow assessment of A/T/N in individual patients using a single imaging session. Cortical tissue clearance (K2a) of [18F]PI-2620 was validated as a surrogate of the β-amyloid status against β-amyloid-PET and cerebrospinal fluid (CSF) Aβ42/40ratio, demonstrating remarkable positive (91.5%) and negative (95.1%) predictive values at an AUC of 0.99 (P<0.0001). K2a outperformed cortical tau burden as a surrogate for β-amyloid status in 47 participants with a clinical diagnosis of probable AD (3/4-repeat(R)-tauopathy) and 82 β-amyloid-negative patients with primary 4R-tauopathies. Perfusion-like [18F]PI-2620 images (R1) were validated as a surrogate marker for neuronal injury, exhibiting strong quantitative and visual correlations with FDG-PET and early-phase β-amyloid-PET, as well as with volumetric MRI and CSF total tau levels. Composite quantitative A/T/N indices facilitated personalized staging along temporal disease trajectories. Our results suggest that [18F]PI-2620 imaging has the potential to facilitate the assessment of region and stage dependent PET-based A/T/N during a single dynamic PET session.

Graphical Abstract
Glymphatic defect in isolated REM sleep behavior disorder is associated with phenoconversion to Parkinson’s disease
Authors: Ayral Violette , Pastor-Bernier Alexandre , Daneault Véronique , Tremblay Christina , Filiatrault Marie , Haddad Celine , Gagnon Jean-François , Postuma Ronald , Dusek Petr , Marecek Stanislav , Varga Zsoka , Klein Johannes , Hu Michele T. , Lehéricy Stéphane , Arnulf Isabelle , Vidailhet Marie , Corvol Jean-Christophe ,   ICEBERG Study Group, Rahayel Shady ,   Quebec Parkinson Network
Published: January 2025

Isolated rapid eye movement (REM) sleep behavior disorder (iRBD) is characterized by the loss of muscle atonia and abnormal, often violent, movements and vocalizations during REM sleep. It is the strongest prodromal marker for progression to synucleinopathies such as dementia with Lewy bodies (DLB) and Parkinson’s disease (PD). iRBD individuals already show brain changes consistent with manifest synucleinopathies, but their mechanisms remain poorly understood. The glymphatic system is involved in the brain clearance of waste products and its defect has been associated with a higher likelihood of pathological burden and neurodegeneration. The presence of glymphatic system dysfunction revealed by neuroimaging in iRBD and its association with disease progression remain uninvestigated, including its potential to predict conversion toward distinct trajectories of synucleinopathies.

We analyzed diffusion-weighted imaging data from a large international multicentric cohort of polysomnography-confirmed iRBD individuals and healthy controls. We used diffusion tensor imaging along the perivascular space to assess glymphatic function and derived a glymphatic index based on the diffusivity occurring within masks placed on associative and projection fibers adjacent to the lateral ventricles. The index was compared between groups and correlated with motor and cognitive features. Cox regression models assessed the relationship between glymphatic index and the likelihood of conversion to PD, DLB or remaining disease-free.

Our analyses included 250 polysomnography-confirmed iRBD participants (mean age 66.5 ± 6.8 years; 87% men) and 178 controls (65.7 ± 6.8 years; 81% men). There was a significantly reduced glymphatic index in iRBD individuals compared to controls. Among the 224 iRBD individuals followed longitudinally (6.1 years, 1-16 years), 65 developed a neurodegenerative disease. iRBD converters exhibited lower glymphatic index compared to non-converters. Lower glymphatic index was associated with a higher risk of phenoconversion towards PD over time compared to remaining disease-free (hazard ratio = 2.43, 95% CI = 1.13-5.25, P = 0.012).

This study reports glymphatic dysfunction in iRBD and its potential for predicting conversion to PD, underscoring its utility in identifying at-risk iRBD individuals.
All-cause and cardiac mortality in relation to smoke exposure nine years after the Hazelwood coal mine fire
Authors: Walker-Bone Karen , Gao Caroline X , Smith Catherine L. , Ye Tingting J , Brown David , Kinsman Natasha , Ikin Jillian F , Carroll Matthew , Abramson Michael J , Guo Yuming , Lane Tyler J
Published: January 2025

BackgroundIn 2014, a coal mine fire in rural Australia shrouded nearby towns in smoke for several weeks. In response to community concerns and a lack of available evidence, the Victorian Department of Health commissioned a long-term health study. This paper evaluates smoke effects on mortality 9-years after the fire.MethodsIn 2016-17, 4,056 members of the exposed community and a demographically-similar control were recruited into a cohort study. A third of these (2,725 (67%)) consented to linkage of their data. To estimate individual-level smoke exposure, participant`s time-location diaries were blended with estimates of hourly fire-related PM2.5based on meteorological and chemical transport models. All-cause mortality data were obtained up to mid-2023 by linkage with the National Death Index. Cardiac-related deaths were identifiable up to December 2021 and predicted thereafter to mid-2023. Differences in all-cause mortality were evaluated with Cox proportional-hazards models and differences in cardiac mortality with a competing risk survival model.ResultsAcross 6-7 years of follow-up, 303 (11%) of the sample died. All-cause mortality was not associated with PM2.5exposure. A 10μg/m3increase in PM2.5was associated with a 17% (95%CI: 1.01-1.36) higher risk of mortality from cardiac causes.DiscussionPM2.5from the mine fire was associated with elevated cardiac mortality between 2-9 years post-exposure. This finding concords with a growing body of evidence after acute exposure to wildfires and chronic exposures from household or ambient air pollution. Measures are needed to protect individuals from exposure to smoke during and after large fire events.
NAMPT activity plays a key role in driving autoimmune processes that characterise type 1 diabetes development in mice
Authors: Egbase Daniel , Sayers Sophie R. , Haq Naila , Varghese Jithu , Bhattacharya Sreya , Kynaston Jay , Hubber Ella L. , Smith Lorna , Pullen Timothy J. , Gerdes Henry , Lee Vivian K. , Hopkins David , Zhao Minh , Cheah Yee , Greally Joshua , Butterworth Sam , Pearson James A , Bewick Gavin , Persaud Shanta , Caton Paul W.
Published: January 2025

Objective

Type 1 diabetes (T1D) is characterised by destruction of pancreatic beta cells by islet-infiltrating cytotoxic lymphocytes, and elevated intra-islet secretion of pro-inflammatory cytokines. However, the underlying pathophysiological mechanisms remain incompletely understood. We hypothesise that abnormal elevation of islet NAD, via activation of NAMPT, plays a key role in driving islet autoimmune processes in T1D, and that conversely, NAMPT inhibition may be an attractive therapeutic approach for T1D.

Methods

Islets were isolated from non-diabetic CD1 mice or obtained from human islet donors and exposed to pro-inflammatory cytokine cocktail (IL-1β, TNFα and IFNγ) +/− NAMPT inhibitor. Beta-cell function was determined by static glucose-stimulated insulin secretion. Islet apoptosis was determined by caspase 3/7 activity. Islet cell differential gene expression was assessed via bulk-RNA sequencing. Diabetes was induced in CD1 mice via multiple low dose streptozotocin (MLDS) injection. MLDS mice were then administered FK866 (10 mg/kg; IP) or saline equivalent for 16 days. Ambient blood glucose was measured every 2-3 days. Beta-cell function was assessed by measurement of serum insulin and c-peptide levels. Insulin content was assessed by flow cytometry. Intra-islet immune cell infiltration, as well as immune cell proliferation and cytokine production were assessed via flow cytometry. For migration assays, islets were isolated from BALB/c mice dispersed and reaggregated into reformed islets. CD8+cells were isolated from splenocytes derived from NY8.3 NOD mice migration of immune cells was assessed using a transwell culture protocol.

Results

NAMPT inhibition with FK866 or compound 17 protected mouse and human islets against cytokine-mediated beta cell dysfunction and death. RNAseq revealed that inhibiting NAMPT blocked pro-inflammatory cytokine-mediated gene expression linked to pro-inflammatory responses and leukocyte migration. FK866 improved glycaemic control and beta-cell function in MLDS mice. FK866 also reduced proportions of islet-residing TNFα producing CD4+T-cells and F4/80+macrophages, proliferation of spleen-derived CD4+and CD8+T-cells, and proliferation of islet-derived CD4+T-cells and F4/80+macrophages. Finally, FK866 was able to block pro-inflammatory cytokine-mediated migration of cytotoxic CD8+T-cells into reformed islets.

Conclusions

This data supports a key immunomodulatory role for NAMPT in islet autoimmunity. NAMPT inhibition may represent a novel therapeutic approach for T1D.
Linalool andtrans-nerolidol prevent pentylenetetrazole-induced seizures in adult zebrafish
Authors: Silva Amanda L. , Bastos Leonardo M. , Gallas-Lopes Matheus , Chitolina Rafael , Reis Carlos G. , Nunes Domingos Sávio , Elisabetsky Elaine , Herrmann Ana P. , Calcagnotto Maria Elisa , Piato Angelo
Published: January 2025

Ethnopharmacological relevance

linalool (LIN) andtrans-nerolidol (NER) are terpene alcohols found in high concentrations in plant-derived essential oils used as a traditional treatment in many cultures. Several studies evaluating the effects of these essential oils and their isolated compounds have shown antiseizure, sedative, neuroprotective, and antioxidant properties in acute seizure models bothin vitroandin vivo. Therefore, this study aimed to evaluate the effects of acute exposure to LIN or NER on a pentylenetetrazole (PTZ)-induced seizure model in adult zebrafish (Danio rerio).

Methods

240 adult wild-type zebrafish were randomly allocated to the experimental groups: control (dechlorinated water), 1% DMSO (vehicle), diazepam (50 µM DZP), and LIN or NER (4, 40 and 400 µM). Animals were exposed to the treatment solution (400 mL) for 10 minutes, taken to a washout beaker (dechlorinated water, 400 mL) for 5 minutes, and recorded in the test apparatus containing 10 mM PTZ for 20 minutes. Experienced researchers conducted a blinded analysis of behavioral seizure phenotypes using BORIS® software. Additionally, locomotor activity was evaluated through ANY-Maze™ tracking software, ensuring precise and unbiased assessment of movement behaviors.

Results

the highest concentration of LIN (400 µM) and NER (40 and 400 µM) increased the latency to reach clonic and tonic-like seizure stages while decreasing the seizure intensity. Interestingly, NER has shown a larger effect size than the positive control group DZP, and at a concentration of 40 µM, increased locomotor behavior.

Conclusion

our findings show the antiseizure properties of LIN and NER in zebrafish acutely exposed to PTZ, delaying the time to reach the highest seizure stages and decreasing seizure intensity. These results are consistent with previous experiments conducted in mice and amplify the external validity of these compounds, highlighting their potential as antiseizure remedy candidates.

Graphical abstract

Created using BioRender.