bluuebunny/crossref_metadata_2025 huggingface dataset:
Temperature dependence of magnetization and gap oscillations in magnetic superconductors
Authors: Burmistrov S. N.
Published: December 2024

The study deals with the possibility of anomalous superconductive and magnetic behavior of a multiply connected ferromagnetic superconductor due to the diamagnetic interaction of superconductive current with the magnetization, when the quantization of the magnetic flux is taken into account. It is demonstrated that the nature and magnitude of the oscillations of the magnetization and of the superconducting gap, with changes in temperature, caused by penetration of magnetic flux into a hollow cylinder of the material depend on the geometrical dimensions of the specimen. Conditions necessary for detecting these oscillations experimentally are also examined.
Effect of Abrikosov vortices on dislocation internal friction in Pb-ln single crystals
Authors: Beloshapka V. Ya. , Platkov V. Ya.
Published: December 2024

The dependence of the damping decrement δ and the modulus defect ΔM/M on the strain amplitude ε0 are studied on single crystals of alloys of lead with indium in the mixed state. For the alloy Pb + 3 at.% In the curves δ (log ε0) in the mixed state are found to shift towards higher values of ε0 with an increase in the magnetic field H. This indicates that the presence of Abrikosov vortices in the lattice causes variations in the effective value of the dislocation damping coefficient. For the alloy Pb + 12 at.% In the curves δ(log ε0) also shift towards high values of ε0 as H increases in the interval Hc1 <H < (Hc1 + Hc)/2 but shift in the opposite direction as H grows further. This nonmonotonic behavior of the shift indicates that Abrikosov vortices act as regions which restrict the motion of dislocations.
Scattering of magnons by dislocations in antiferromagnets
Authors: Breus S. A. , Sobolev V. L.
Published: December 2024

We have studied theoretically the damping of low frequency magnons in an easy plane antiferromagnet with linear, randomly distributed dislocations. We have explored systematically the concomitant dislocation broadening of the antiferromagnetic resonance line.
Perturbation-induced evolution of a soliton–antisoliton pair in the sine-Gordon system
Authors: Kosevich A. M. , Kivshar’ Yu. S.
Published: December 2024

The evolution of a soliton–antisoliton solution of the perturbed sine-Gordon equation is studied, using a perturbation theory for solitons which is based on the inverse scattering method. The following processes are described within the adiabatic approximation: soliton and antisoliton annihilation under the action of friction with the formation of a bound state, a bion; generation of a quasibound soliton–antisoliton pair in an external constant field; and the effect of an external field on soliton–antisoliton scattering in a dissipative system. The nature of these processes depends substantially on the initial parameter values of the colliding solitary waves. To first approximation, the perturbation is shown to generate no new soliton–antisoliton pairs and bions, thus making it possible to confine the analysis to the adiabatic approximation only.
Effect of the rotational motion of N2 impurity molecules on the thermal expansion of solid Ar
Authors: Azarenkov V. P. , Tolkachev A. M. , Aleksandrovskii A. N. , Kosobutskaya E. A.
Published: December 2024

An excess coefficient of linear expansion Δα of solid Ar with N2 as an impurity is discovered in the temperature range 2–12° K. The quantity Δα depends linearly on the concentration in the interval n = 1.02–2.03% N2; for 3.27% a small derivation from linearity is observed, which is due to the interaction between impurity molecules. The anomaly in the thermal expansion is explained by librations of N2 impurity molecules in Ar up to their free rotation. The relative increase in the volume of the crystal, necessary for free rotation of the impurity molecule, corresponding to the effect, is calculated. Its small magnitude is related to the large angles of zero-point librations of a diatomic molecule in an environment of spherically symmetric neighbors.
Localization effects in bismuth films in a weak magnetic field
Authors: Komnik Yu. F. , Bukhshtab E. I. , Butenko A. V. , Andrievskii V. V.
Published: December 2024

The magnetoresistance of thin (L ∼ 95–200 Å) bismuth films in a weak magnetic field, oriented perpendicular or parallel to the plane of the films, is investigated. The magnetoresistance, due to localization of electrons, increases quadratically with increasing magnetic field. A sharp anisotropy effect is observed: The magnitude of the localization correction in the perpendicular field is almost an order of magnitude greater than in the parallel field. These results agree well with the theory of localization of electrons in two-dimensional systems. The temperature dependence of the inelastic relaxation time of electrons is discussed.
Scriptural Vitality
Authors: Najman Hindy
Published: December 2024

Scriptural Vitality challenges the view that the Persian and Hellenistic periods constitute a time of decay, a period of ‘late Judaism’, languishing between an original, vibrant Judaism and the birth of Christianity. Instead, this book argues that the Second Temple period was one of untethered creativity and poetic imagination, of dynamism exemplified through philosophical translation, poetic composition, and a convergence of ancient Mediterranean cultures that gave birth to hermeneutic innovation. Building on Nietzsche’s critique of classical philology and drawing on new ways of reading the Dead Sea Scrolls, the book carries out a radical rethinking of biblical studies. Instead of seeking to reconstruct the original text and to find its original author or at least the original context of its production, Najman celebrates textual pluriformity and transformation, tracing ways in which texts and meanings proliferated within interpretive communities through new performances and fresh articulations of the past. Engaging with thinkers such as Friedrich Schlegel and Peter Szondi, whom biblicists have rarely considered, biblical philology is reimagined as the forward-moving study of the poetic processes by which Jewish communities re-created their past and revitalized their present. The Second Temple period emerges as a golden age of creativity, whose traces may still be discerned in Judaism and Christianity today.
Formation of the Subject in Hellenistic Judaism
Authors: Najman Hindy
Published: December 2024

The Hellenistic period of ancient Judaism exhibits entanglement as an expression of vitality in which strands of Jewish thinking and Greek thinking are temporarily intertwined. Far from being bereft of complex thinking patterns, this period produces innovative engagement with philosophical questions about subjecthood, transformation, and perfection. The concept of imitatio dei or betselem Elohim captures an interior aspiration towards the formation of the self insofar as the subject is formed and it relates to its own perfection. The aspiration is not to be divinized, but rather to be angel-like, godlike, which is also to aspire to humanity. Though this imitation of the divine is always incomplete, it is the essence of every subject. The emergence of the self as the image of God happens precisely at a time when practice, ritual, and even sacrifice are internalized and translated onto the body and the practices of the individual, thereby internalizing the role of the prophetic. This account contrasts against the reconstruction of the historical origins of the Western concept of selfhood in the classical Greek and Roman world and subsequently transmitted through Christianity. The uncritical adoption of this framework in much of biblical scholarship has effaced the ancient Jewish contribution. Therefore, the Jewish voice with respect to subjecthood should be integrated into the larger conceptual framework and intellectual history of this discourse.
Cheese
Authors: Kelly Alan , Fox Patrick , Cogan Tim
Published: December 2024

This chapter considers the origins of cheese and provides an overview of the principles involved in its manufacture and ripening (during which flavor develops). It describes some of the organisms involved in cheese spoilage, as well as how pathogens occasionally occur and grow in cheese. The chapter goes on to describe how cheeses are classified, along with patterns of their consumption, and briefly introduces the principles of manufacture of several important varieties, including Cheddar, blue, Swiss, and feta cheeses. The chapter is illustrated with images of the main cheese types.
Fermented Milks
Authors: Kelly Alan , Fox Patrick , Cogan Tim
Published: December 2024

This chapter introduces fermented milks, which are some of the oldest and most widespread dairy products, relatively easy to produce, and with an extended shelf-life compared to raw milk. It describes the production and manufacture of several of the important fermented milks, including yoghurt, cultured buttermilk, sour cream, kefir, and koumiss, which is made from mare’s milk. The chapter also describes Scandinavian, Middle Eastern, Indian fermented milks and the Japanese product, Yakult. Finally it considers the role of probiotic bacteria and the range of health benefits attributed to including them in the human diet.
The Production of Milk Protein Ingredients and Lactose
Authors: Kelly Alan , Fox Patrick , Cogan Tim
Published: December 2024

This chapter considers products derived from milk and the by-products of the manufacture of dairy products. Milk is increasingly the starting point for making a huge range of fractionated products and ingredients, from whey protein powders sold in gyms for body-building to lactose used in the preparation of pharmaceutical tablets. The chapter relates how the oldest example of this is probably the way in which whey, a by-product of cheesemaking, was transformed from a perceived waste disposal problem for much of the history of cheese-making, to a highly valued source of a range of ingredients that today are used in a huge range of applications. It also explains that milk proteins are being increasingly recovered by a range of processes to yield a range of high-value protein ingredients such as those based on purified casein. The chapter describes these products, along with the key technology involved in producing many of them, filtration through ultrafine membranes that act as sieves, the dimensions of which can be tailored to separate different sized molecules with exquisite precision.
Human Milk and Infant Formula
Authors: Kelly Alan , Fox Patrick , Cogan Tim
Published: December 2024

Infant formula is probably one of the most complex dairy products. This chapter describes the many complex formulation and processing considerations that are required to transform cows’ milk into a product that more closely resembles human milk, to provide optimal nutrition to infants at a key stage of their life and development. The chapter also outlines the properties and composition of human milk, as an understanding of these is critical to understanding the requirements for infant formula composition. It also provides a short description of how infant formula is handled and preserved compared to bovine milk. The formulation and processing of different kinds of infant formula (including dry and liquid formulae and formulae for different stages of infancy), using many of the processes described in previous chapters, are then discussed.
Yes I can! Exploring the impact of self-efficacy in a digital weight loss intervention
Authors: Cleare Angel E , Gardner Christopher D , King Abby C , Patel Michele L
Published: December 2024

Background

Self-efficacy is a modifiable intervention target in behavioral weight loss interventions. However, its role in the context of digital interventions is less clear.

Purpose

To determine change in self-efficacy in a digital weight loss intervention, and whether self-efficacy is associated with engagement in self-monitoring diet or weight loss.

Methods

This is a secondary analysis of the GoalTracker study among 100 adults with overweight or obesity enrolled in a 12-week standalone digital weight loss intervention emphasizing daily self-monitoring. At baseline, 1 month, and 3 months, we assessed self-efficacy for controlling eating (via the Weight Efficacy Lifestyle Questionnaire; WELQ) and self-efficacy for tracking diet. Dietary self-monitoring engagement data were collected from the MyFitnessPal app. Weight was collected in person on a calibrated scale. Analyses included participants with complete data (N range: 72-99).

Results

Positive change from baseline to 1 month in self-efficacy for controlling eating was associated with higher dietary self-monitoring engagement (r = 0.21, P = .008) but not with 3-month weight change (r = –0.20, P = .052). Meanwhile, positive change from baseline to 1 month in self-efficacy for tracking diet was associated in a beneficial direction with both outcomes (r = 0.57, P < .001; r = –0.35, P < .001, respectively). However, on average, self-efficacy for controlling eating did not change over time while self-efficacy for tracking diet decreased (P < .001).

Conclusion

Improvements in self-efficacy—particularly for tracking diet—early on in a digital weight loss intervention served as a mechanism of greater engagement and weight loss, highlighting the need for strengthening intervention strategies that promote early self-efficacy within a digital context.
Remake as resistance: re-narrating Hong Kong Chineseness in The Taking of Tiger Mountain
Authors: Zhang Zoe Yi
Published: December 2024

It is often assumed that yangban-xi (model theatre), crafted by the Chinese Communist Party during the Cultural Revolution (1966–76), represents a homogeneous Chinese identity. However, this assumption overlooks the intricate cultural, economic, and political dynamics embedded in these works, especially when remade by Sinophone artists. Following the 2003 Closer Economic Partnership Arrangement (CEPA), these dynamics are further complicated by increasingly blurred boundaries between Hong Kong and mainland China. This paper examines The Taking of Tiger Mountain (Zhiqu weihu shan) (Tsui Hark 2014), a Hong Kong-Mainland coproduced remake of a yangban-xi film. Through an analysis of the film’s intertextual connections with its 1970 predecessor and its genre-blending and narrative strategies, this study argues that the remake challenges the authority of official history by exposing fissures in collective memory and the inherent subjectivity in historical narratives. The paper posits The Taking of Tiger Mountain as a cultural battleground where the top-down homogeneity of ‘Chineseness’ is contested by diverse peripheral voices, reflecting the ongoing negotiation of cultural identities within the post-1997 Hong Kong-Mainland context.
Trajectories of functional decline and predictors in long-term care settings: a retrospective cohort analysis of Canadian nursing home residents
Authors: Egbujie Bonaventure Amandi , Turcotte Luke Andrew , Heckman George , Hirdes John P
Published: December 2024

Decline in the ability to perform activities of daily living (ADL) or ‘functional decline’ is a major health concern among aging populations. With intervention, ADL decline may be delayed, prevented or reversed. The capacity to anticipate the trajectory of future functional change can enhance care planning and improve outcome for residents.

Methods

This is a 36 months’ retrospective longitudinal analysis of LTC residents in five Canadian provinces. Group-based trajectory modelling (GBTM) was performed to identify distinct trajectories and resident attributes associated with membership of the trajectory groups.

Results

A total of 204 036 LTC residents were included in this study. Their admission mean age was 83.7 years (SD = 8.6), and 63.3% were females. Our model identified four distinct trajectories namely: ‘Catastrophic decline’ (n = 48 441, 22.7%), ‘Rapid decline with some recovery’ (n = 27 620, 18.7%), ‘Progressive decline’ trajectory (n = 30 287, 14.4%), and the ‘No/Minimal decline’ (n = 97 688, 47.9%) Residents’ admission ADL Hierarchy score was the single, strongest predictor of functional decline trajectory that residents followed. Residents with ADLH 5–6 OR 0.03 (0.03–0.04) were least likely to follow a catastrophic decline trajectory, while those with ADLH 5–6 OR 39.05 (36/60–41.88) were most likely to follow a minimal or no decline trajectory.

Conclusion

Results of this study further highlight the heterogeneity of health trajectory among residents in LTC setting, re-affirming the need for personalized care. The study shows who among residents would be most at risk for different levels of functional decline.

The study findings provide useful information that would assist both immediate and advanced care planning as well as to forecast care personnel requirements into the future based on total acuity levels of residents.
Frailty reduces penumbral volumes and attenuates treatment response in hyperacute ischemic stroke
Authors: Dohle Esmee , Lewis Benjamin , Agarwal Smriti , Warburton Elizabeth A , Evans Nicholas R
Published: December 2024

Background

Frailty—the loss of physiological reserve to withstand a stressor event—is associated with poorer outcomes following acute stroke reperfusion therapies. However, the mechanisms underlying this relationship are poorly understood. This study investigated the association between frailty and penumbral volumes in hyperacute ischemic stroke.

Methods

Total ischemic lesion volumes (comprising infarct core and penumbral volumes) were measured using computed tomography (CT) perfusion imaging to give the penumbral fraction within the ischemic lesion. Pre-stroke frailty was measured using a validated frailty index. The relationship between frailty and penumbral fraction was adjusted for age, onset-to-CT interval, collateral scores, small vessel disease burden and vascular comorbidities. Stroke severity was measured using the National Institutes of Health Stroke Scale at baseline and after 24 h.

Results

In 55 individuals receiving thrombolysis for ischemic stroke, increasing frailty was associated with a reduction in penumbral fraction (rs = −0.36, P < 0.01). This remained significant after adjustment for age, onset-to-imaging time and collateral score (beta = −1.16, P < 0.001). Correspondingly, frailty was independently negatively associated with proportional improvement in stroke severity following treatment (beta = −2.00, P < 0.01). C-reactive protein (CRP) on presentation was associated with frailty index (rs = 0.38, P < 0.01) and penumbral fraction (rs = −0.30, P = 0.02).

Discussion

A reduction in salvageable penumbra in frailty may explain the treatment-attenuating effects of frailty on reperfusion therapies. The association with CRP motivates further research into a possible inflammatory component of this relationship.

Conclusion

Frailty is independently associated with reduced penumbra and poorer neurological recovery in acute stroke. These findings may explain the attenuated response to stroke reperfusion therapies seen in frailer individuals.
Sample composition and HIV prevention indicator differences using physical vs. virtual venue recruitment of men who have sex with men in San Francisco
Authors: Chiu Izzy , Tate Moranda , Trujillo Dillon , Suprasert Bow , Marr Alex , Arayasirikul Sean , Wilson Erin C , Raymond Henry F , McFarland Willi
Published: December 2024

During the COVID-19 pandemic, the sampling method for the National HIV Behavioral Surveillance (NHBS) in San Francisco changed from physical venue time-location sampling (TLS) to online or virtual venue TLS for men who have sex with men (MSM). We present differences in the samples of MSM recruited using physical venue TLS in 2017 and virtual venue TLS in 2021. We further assess changes in preventive and risk behaviors from 2017 to 2021 after controlling for differences in the sample compositions with multivariable Poisson models using GLM with robust standard errors. Both sampling methods exceeded their targeted sample size of 500 (physical venue TLS n=502, virtual venue TLS n=505). Compared to physical venue TLS, the virtual venue TLS sample had fewer persons experiencing homelessness and incarceration, and more persons with health insurance and post-graduate degrees. After adjusting for these differences and age, race, and employment status, PrEP use increased from 2017 to 2021. The use of several non-injection drugs also increased, namely marijuana, poppers, ketamine, psilocybin, and LSD. We found virtual venue recruitment of MSM to be a viable approach for tracking trends in HIV-related behaviors, with notable appeal given possible future pandemic lockdowns of physical venues and changing socialization patterns.
Understanding lipidomics associations and the lipoprotein-related caveats in population epidemiology
Authors: Zhao Siyu , Ohukainen Pauli , Kettunen Johannes , Järvelin Marjo-Riitta , Kähönen Mika , Lehtimäki Terho , Viikari Jorma , Raitakari Olli T , Mäkinen Ville-Petteri , Ala-Korpela Mika
Published: December 2024

Mass spectrometry lipidomics is becoming customary to analyse serum/plasma samples in epidemiology. The measurables are molecular constituents of lipoprotein particles, but very little is known on the consequences of adjusting lipidomics data with lipoprotein measures. We studied two population cohorts with 5,657 and 2,036 participants. LC-MS/MS lipidomics was applied to analyse 24 molecular lipid classes and NMR spectroscopy to quantify seven lipoprotein lipids plus apolipoprotein A-I (apoA-I) and B (apoB). The associations of these measures were analysed via partial Spearman’s correlations. The effects of nine different lipoprotein adjustments on these interrelationships were assessed. Multivariable regression modelling with these adjustments was also performed for the associations between the lipidomics data and BMI. These novel large-scale lipidomics data and their associations between the lipoprotein measures were coherent in both population cohorts, confirming the compatibility of the analytical approaches. Simulated data were generated to corroborate the mediation effects. The lipoprotein-related lipid-transport and metabolism inherently mediate the lipidomics associations as evident from the striking effects of the lipoprotein adjustments. These effects and their relevance to the interpretations of lipidomics data are presented and discussed in detail for the first time. The combined lipoprotein lipid adjustments appear prone to overadjustment and arbitrary biases.
Effects of hypothetical low versus moderate-to-high intensity weight management regimens on knee replacements
Authors: Miki Takahiro , Cooray Upul , Kanai Masashi , Hagiwara Yuta , Murakami Masayasu , Osaka Ken , Ikeda Takaaki
Published: December 2024

This study aimed to investigate the efficacy of a hypothetical biennial weight management regimen in reducing the necessity for knee replacement (KR) surgery among middle-aged and older adults with or at a higher risk for knee osteoarthritis (OA). Data from the Osteoarthritis Initiative cohort in the US, comprising community-dwelling adults aged 45–79 years at high risk for or with symptomatic knee OA who underwent baseline assessments from September 2008 to December 2010 were used. Subsequent evaluations were conducted at 12, 24, and 96 months. A hypothetical biennial weight management regimen, ranging from low to moderate-to-high intensity, was employed as the exposure, whereas the incidence of KR during follow-up was the outcome. This study, using a targeted learning approach to estimate hypothetical weight management regimens adjusted for time-varying confounding and attrition due to loss to follow-up, revealed that a 7.5% reduction in body mass index (high-intensity) resulted in a notable decrease in KR rates, from 5.93% [95% confidence interval (CI), 5.64–6.21] in the baseline maintenance regimen (low-intensity) to 3.60% (95% CI, 2.70–4.50) in the high-intensity regimen. In conclusion, a hypothetical weight management regimen significantly reduces the need for KR surgery in adults with knee OA.
Towards Robust Causal Inference in Epidemiological Research: Employing Double Cross-fit TMLE in Right Heart Catheterization Data
Authors: Mondol Momenul Haque , Karim Mohammad Ehsanul
Published: December 2024

Within epidemiological research, estimating treatment effects from observational data presents notable challenges. Targeted Maximum Likelihood Estimation (TMLE) emerges as a robust method, addressing these challenges by accurately modeling treatment effects. This approach uniquely combines the precision of correctly specified models with the versatility of data-adaptive, flexible machine learning algorithms. Despite its effectiveness, TMLE’s integration of complex algorithms can introduce bias and under-coverage. This issue is addressed through the Double Cross-fit TMLE (DC-TMLE) approach, enhancing accuracy and reducing biases inherent in observational studies. However, DC-TMLE’s potential remains underexplored in epidemiological research, primarily due to the lack of comprehensive methodological guidance and the complexity of its computational implementation. Recognizing this gap, our paper contributes a detailed, reproducible guide for implementing DC-TMLE in R, aimed specifically at epidemiological applications. We demonstrate the utility of this method using an openly available clinical dataset, underscoring its relevance and adaptability for robust epidemiological analysis. This guide aims to facilitate broader adoption of DC-TMLE in epidemiological studies, promoting more accurate and reliable treatment effect estimations in observational research.
Estimating the undetected burden and the likelihood of strain persistence of drug-resistant Neisseria gonorrhoeae
Authors: Oliveira Roster Kirstin I , Rönn Minttu M , Elder Heather , Gift Thomas L , Roosevelt Kathleen A , Salomon Joshua A , Hsu Katherine K , Grad Yonatan H
Published: December 2024

Neisseria gonorrhoeae has developed resistance to all antibiotics recommended for treatment and reports of reduced susceptibility to ceftriaxone, the last-line treatment, are increasing. Since many asymptomatic infections remain undiagnosed and most diagnosed infections do not undergo antibiotic susceptibility testing, surveillance systems may underestimate resistant infections. In this modeling study, we simulated the spread of a new strain of ceftriaxone non-susceptible N. gonorrhoeae in a population comprising men who have sex with men as well as heterosexual men and women. We compared scenarios with varying strain characteristics and surveillance capacity. For each scenario, we estimated (i) the number of undetected infections of the novel strain and (ii) the likelihood of strain persistence in the absence of newly reported cases. Upon detection of one non-susceptible isolate, the undetected burden was an estimated 5.4 infections with substantial uncertainty (0-18 infections, 95% uncertainty interval). Without additional reports of non-susceptible infections over the subsequent 180 days, the estimate declined to 2.5 infections (0-10 infections). The likelihood of ongoing transmission also declined from 66% (26-86%) at first detection to 2% (0-10%) after 180 days. To extend the useful lifespan of last-line antibiotics, our model estimated the infection landscapes that could underlie data from surveillance systems.
One organ to infect them all: the Cuscuta haustorium
Authors: Balios Vasili A , Fischer Karsten , Bawin Thomas , Krause Kirsten
Published: December 2024

Background

Research on the parasitic plant genus Cuscuta has flourished since the genomes of several of its species were published. Most of the research revolves around the iconic infection organ that secures the parasite’s sustenance: the haustorium. Interest in understanding the structure–function–regulation relationship of the haustorium is based as much on the wish to find ways to keep the parasite under control as on the opportunities it offers to shed light on various open questions in plant biology.

Scope

This review will briefly introduce parasitism among plants, using the genus Cuscuta as the main example, before presenting its haustorium alongside the terminology that is used to describe its architecture. Possible evolutionary origins of this parasitic organ are presented. The haustorium is then followed from its initiation to maturity with regard to the molecular landscape that accompanies the morphological changes and in light of the challenges it must overcome before gaining access to the vascular cells of its hosts. The fact that Cuscuta has an unusually broad host range stresses how efficient its infection strategy is. Therefore, particular consideration will be given in the final section to a comparison with the process of grafting, being the only other type of tissue connection that involves interspecific vascular continuity.

Conclusions

Studies on Cuscuta haustoriogenesis have revealed many molecular details that explain its success. They have also unearthed some mysteries that wait to be solved. With a better understanding of the complexity of the infection with its combination of universal as well as host-specific elements that allow Cuscuta to parasitize on a wide range of host plant species, we may be many steps closer to not only containing the parasite better but also exploiting its tricks where they can serve us in the quest of producing more and better food and fodder.
RIOT—Rapid Immunoglobulin Overview Tool—annotation of nucleotide and amino acid immunoglobulin sequences using an open germline database
Authors: Dudzic Paweł , Janusz Bartosz , Satława Tadeusz , Chomicz Dawid , Gawłowski Tomasz , Grabowski Rafał , Jóźwiak Przemek , Tarkowski Mateusz , Mycielski Maciej , Wróbel Sonia , Krawczyk Konrad
Published: December 2024

Antibodies are a cornerstone of the immune system, playing a pivotal role in identifying and neutralizing infections caused by bacteria, viruses, and other pathogens. Understanding their structure, and function, can provide insights into both the body’s natural defenses and the principles behind many therapeutic interventions, including vaccines and antibody-based drugs. The analysis and annotation of antibody sequences, including the identification of variable, diversity, joining, and constant genes, as well as the delineation of framework regions and complementarity-determining regions, is essential for understanding their structure and function. Currently analyzing large volumes of antibody sequences is routine in antibody discovery, requiring fast and accurate tools. While there are existing tools designed for the annotation and numbering of antibody sequences, they often have limitations such as being restricted to either nucleotide or amino acid sequences; slow execution times; or reliance on germline databases that are closed, frequently changed, or have sparse coverage for some species. Here, we present the Rapid Immunoglobulin Overview Tool (RIOT), a novel open-source solution for antibody numbering that addresses these shortcomings. RIOT handles nucleotide and amino acid sequence processing, comes integrated with an Open Germline Receptor Database, and is computationally efficient. We hope that the tool will facilitate rapid annotation of antibody sequencing outputs for the benefit of understanding antibody biology and discovering novel therapeutics.
epiTCR-KDA: knowledge distillation model on dihedral angles for TCR-peptide prediction
Authors: Pham My-Diem Nguyen , Su Chinh Tran-To , Nguyen Thanh-Nhan , Nguyen Hoai-Nghia , Nguyen Dinh Duy An , Giang Hoa , Nguyen Dinh-Thuc , Phan Minh-Duy , Nguyen Vy
Published: December 2024

Motivation

The prediction of the T-cell receptor (TCR) and antigen bindings is crucial for advancements in immunotherapy. However, most current TCR-peptide interaction predictors struggle to perform well on unseen data. This limitation may stem from the conventional use of TCR and/or peptide sequences as input, which may not adequately capture their structural characteristics. Therefore, incorporating the structural information of TCRs and peptides into the prediction model is necessary to improve its generalizability.

Results

We developed epiTCR-KDA (KDA stands for Knowledge Distillation model on Dihedral Angles), a new predictor of TCR-peptide binding that utilizes the dihedral angles between the residues of the peptide and the TCR as a structural descriptor. This structural information was integrated into a knowledge distillation model to enhance its generalizability. epiTCR-KDA demonstrated competitive prediction performance, with an area under the curve (AUC) of 1.00 for seen data and AUC of 0.91 for unseen data. On public datasets, epiTCR-KDA consistently outperformed other predictors, maintaining a median AUC of 0.93. Further analysis of epiTCR-KDA revealed that the cosine similarity of the dihedral angle vectors between the unseen testing data and training data is crucial for its stable performance. In conclusion, our epiTCR-KDA model represents a significant step forward in developing a highly effective pipeline for antigen-based immunotherapy.

Availability and implementation

epiTCR-KDA is available on GitHub (https://github.com/ddiem-ri-4D/epiTCR-KDA).
SurfR: Riding the wave of RNA-seq data with a comprehensive bioconductor package to identify surface protein-coding genes
Authors: Maurizio Aurora , Tascini Anna Sofia , Morelli Marco J
Published: December 2024

Motivation

Proteins at the cell surface connect signaling networks and largely determine a cell’s capacity to communicate and interact with its environment. In particular, variations in transcriptomic profiles are often observed between healthy and diseased cells, leading to distinct sets of cell-surface proteins. For these reasons, cell-surface proteins may act as biomarkers for the detection of cells of interest in tissues or body fluids, are often the target of pharmaceutical agents, and hold significant promise in the clinical practice for diagnosis, prognosis, treatment development, and evaluation of therapy response. Therefore, implementing robust methods to identify condition-specific cell-surface proteins is of pivotal importance to advance biomedical research.

Results

We developed SurfR, an R/Bioconductor package providing a streamlined end-to-end workflow for computationally identifying surface protein-coding genes from expression data. Our user-friendly, comprehensive workflow performs systematic expression data retrieval from public databases, differential gene expression across conditions, integration of datasets, enrichment analysis, identification of targetable proteins on a condition of interest, and data visualization

Availability and implementation

SurfR is released under GNU-GPL-v3.0 License. Source code, documentation, examples, and tutorials are available through Bioconductor (http://www.bioconductor.org/packages/SurfR). RMD notebooks with the use cases code described in the manuscript can be found on GitHub (https://github.com/auroramaurizio/SurfR_UseCases).
JARVIS3: an efficient encoder for genomic data
Authors: Sousa Maria J P , Pinho Armando J , Pratas Diogo
Published: December 2024

Motivation

Large-scale genomic projects grapple with the complex challenge of reducing medium- and long-term storage space and its associated energy consumption, monetary costs, and environmental footprint.

Results

We present JARVIS3, an advanced tool engineered for the efficient reference-free compression of genomic sequences. JARVIS3 introduces a pioneering approach, specifically through enhanced table memory models and probabilistic lookup-tables applied in repeat models. These optimizations are pivotal in substantially enhancing computational efficiency. JARVIS3 offers three distinct profiles: (i) rapid computation with moderate compression, (ii) a balanced trade-off between time and compression, and (iii) slower computation with significantly higher compression ratios. The implementation of JARVIS3 is rooted in the C programming language, building upon the success of its predecessor, JARVIS2. JARVIS3 shows substantial speed improvements relative to JARVIS2 while providing slightly better compression. Furthermore, we provide a versatile C/Bash implementation, facilitating the application in FASTA and FASTQ data, including the capability for parallel computation. In addition, JARVIS3 includes a mode for outputting bit information, as well as providing the Normalized Compression and bit rates, facilitating compression-based analysis. This establishes JARVIS3 as an open-source solution for genomic data compression and analysis.

Availability and implementation

JARVIS3 is freely available at https://github.com/cobilab/jarvis3.
DiffPaSS—high-performance differentiable pairing of protein sequences using soft scores
Authors: Lupo Umberto , Sgarbossa Damiano , Milighetti Martina , Bitbol Anne-Florence
Published: December 2024

Motivation

Identifying interacting partners from two sets of protein sequences has important applications in computational biology. Interacting partners share similarities across species due to their common evolutionary history, and feature correlations in amino acid usage due to the need to maintain complementary interaction interfaces. Thus, the problem of finding interacting pairs can be formulated as searching for a pairing of sequences that maximizes a sequence similarity or a coevolution score. Several methods have been developed to address this problem, applying different approximate optimization methods to different scores.

Results

We introduce Differentiable Pairing using Soft Scores (DiffPaSS), a differentiable framework for flexible, fast, and hyperparameter-free optimization for pairing interacting biological sequences, which can be applied to a wide variety of scores. We apply it to a benchmark prokaryotic dataset, using mutual information and neighbor graph alignment scores. DiffPaSS outperforms existing algorithms for optimizing the same scores. We demonstrate the usefulness of our paired alignments for the prediction of protein complex structure. DiffPaSS does not require sequences to be aligned, and we also apply it to nonaligned sequences from T-cell receptors.

Availability and implementation

A PyTorch implementation and installable Python package are available at https://github.com/Bitbol-Lab/DiffPaSS.
Roe deer uterine fluid metabolome reveals elevated glycolysis, fatty acid breakdown, and spermidine synthesis upon reactivation from diapause
Authors: Elsafadi Sara , Hankele Anna-Katharina , Giesbertz Pieter , Ulbrich Susanne E
Published: December 2024

The blastocyst of the European roe deer (Capreolus capreolus) undergoes a period of decelerated growth and limited metabolism. During this period known as embryonic diapause, it floats freely in the uterus encircled by the histotroph. Prior to implantation, reactivation is marked by rapid embryonic growth and conceptus elongation. We hypothesized that the uterine fluid, which is known to undergo changes in its composition to support early embryonic development, contributes to controlling embryonic growth during diapause and elongation. We therefore characterized the pre-implantation uterine fluid metabolome during diapause and at elongation by mass spectrometry and particularly assessed nonpolar lipids, polar metabolites, acylcarnitines, and polyamines. Our results show that triglycerides and diglycerides levels decreased at elongation, likely serving as a source for membrane synthesis rather than for energy production. A functional analysis identified glycolysis as a key pathway during elongation, which may compensate for the energy requirements during this phase. We also observed an increase of sphingomyelin; prostaglandin precursors; and the amino acids asparagine, glutamine, and methionine upon elongation. The sphingolipid and glycerophospholipid metabolism pathways were implicated during elongation. Particularly, spermidine, and to some extent spermine but not putrescine-levels significantly increased in the uterine fluid during elongation, indicating their significance for reactivation and/or proliferation at embryo elongation. We conclude that the roe deer uterine fluid sustained dynamic compositional changes necessary to support the energy- and resource-intensive conceptus elongation. However, it remains to be determined whether these changes are the cause or a consequence of embryo elongation. Studying the metabolic changes and molecular interactions in the roe deer during diapause and elongation not only reveals insights into aspects of its reproductive strategy, but also deepens our knowledge of embryo metabolic demands and developmental velocities across species.
Directed evolution of peroxidase DNAzymes by a function-based approach
Authors: Bhuyan Soubhagya K , He Weisi , Cui Jingyu , Tanner Julian A
Published: December 2024

Peroxidase DNAzymes are single-stranded, stable G-quadruplexes structures that exhibit catalytic activity with cofactor hemin. This class of DNAzymes offers several advantages over traditional protein and RNA catalysts, including thermal stability, resistance to hydrolysis, and easy of synthesis in the laboratory. However, their use in medicine, biology, and chemistry is limited due to their low catalytic rates. Selecting and evolving for higher catalytic rates has been challenging due to limitations in selection methodology which generally use affinity as the selection pressure instead of kinetics. We previously evolved a new peroxidase DNAzyme (mSBDZ-X-3) through a directed evolution method, which was subsequently used for proximity labelling in a proteomic experiment in cell culture. Herein, we present a detailed protocol for this function-based laboratory evolution method to evolve peroxidase DNAzymes for future laboratory implementation. This approach is based on capturing self-biotinylated DNA, which is catalyzed by intrinsic peroxidase activity to select for DNAzyme molecules. The selection method uses fluorescence-based real-time monitoring of the DNA pools, allowing for the enrichment of catalytic activity and capture of catalytic DNA across evolutionary selection rounds.

The evolved mSBDZ-X-3 DNAzyme attributes parallel G-quadruplex structure and demonstrates better catalytic properties than DNAzyme variants evolved previously. The influence of critical reaction parameters is outlined. This protocol enables discovery of improved peroxidase DNAzyme/RNAzyme variants from natural or chemical-modified nucleotide libraries. The approach could be applicable for the selection of catalytic activities in a variety of directed molecular evolution contexts.
Addition of contrast-enhanced mammography enhancement patterns and morphology for differentiating benign from malignant papillary breast lesions
Authors: Xu Weimin , Chen Lingjian , Zeng Weixiong , Xu Zeyuan , Ma Mengwei , Chen Weiguo , Liao Xin , Wen Chanjuan , Wang Sina
Published: December 2024

Objectives

To investigate the capability of morphological and enhancement pattern analysis in contrast-enhanced mammography (CEM) to differentiate between benign and malignant papillary breast lesions.

Methods

This study involved 63 patients diagnosed with papillary breast lesions between January 2018 and December 2022. CEM was performed at two time intervals: between 2-3 min (T1, early phase) and 4-5 min (T2, later phase) after the injection of the contrast agent. For each patient, Breast Imaging Reporting and Data System (BI-RADS) lesion features were recorded. Kinetic enhancement patterns were evaluated for both phases based on these changes, followed by the measurement of diagnostic performance.

Results

Among the 63 female patients, a total of 86 lesions were identified, including 18 malignant ones, three intraductal papillomas without atypical proliferation, and 42 benign papillary lesions. The areas under receiver operating characteristic curves for CEM with kinetic enhancement and for CEM alone were 0.856 and 0.800, respectively. Assessing the diagnostic value, specificity, and accuracy of morphological categorization combined with kinetic enhancement showed higher values compared to those of the CEM morphological categorization alone (71.1% vs 60.0% and 79.4% vs 71.4%, respectively). However, the sensitivity and negative predictive value of the CEM with kinetic enhancement were similar to those of CEM alone (100% for all).

Conclusion

For BI-RADS 3-5 papillary breast lesions, incorporating CEM kinetic enhancement to morphological patterns improved the confidence level in diagnosis.

Advances in knowledge

This article provides valuable references for distinguishing benign and malignant breast papillary lesions.
Postoperative complications after breast cancer surgery and effect on recurrence and survival: population-based cohort study
Authors: Adwall Linda , Fredriksson Irma , Hultin Hella , Mani Maria , Norlén Olov
Published: December 2024

Background

There is conflicting evidence regarding whether postoperative complications after breast cancer surgery are associated with worse oncological outcome. This study aimed to assess the risk of systemic breast cancer recurrence after surgical site infection and also the impact of surgical site infection on locoregional recurrence, breast cancer-specific survival and overall survival.

Methods

This nationwide cohort study included patients who underwent surgery for primary breast cancer in Sweden between January 2008 and September 2019. The study cohort was identified in the Breast Cancer Database Sweden 3.0, a database linking the National Breast Cancer Quality Register to national population-based healthcare registers held by the National Board of Health and Welfare and Statistics Sweden. The primary exposure was surgical site infection within 90 days from surgery, and the primary outcome was systemic recurrence of breast cancer. Secondary outcomes included locoregional recurrence, overall survival and breast cancer-specific survival. Multivariable Cox regression analysis was performed to assess the association between exposure, predictors and outcomes.

Results

Of 82 102 patients included in the study, 15.7% experienced a surgical site infection within 90 days of surgery. Surgical site infection was not significantly associated with systemic recurrence, locoregional recurrence or breast cancer-specific survival after adjustment for confounding variables. Surgical site infection was significantly associated with worse overall survival, but the significant association disappeared in a sensitivity analysis excluding all patients with any kind of malignancy before breast cancer diagnosis.

Conclusion

Surgical site infection after breast cancer surgery does not significantly increase the risk of systemic recurrence. All possible actions should nevertheless be taken to reduce complication rates.
Focusing on the fellas: Stacey Abrams’ social media campaign addresses misogynoir in U.S. politics
Authors: Grant Rachel , Lyons Nikki L
Published: December 2024

After narrowly losing the Georgia (US) gubernatorial election in 2018, Stacey Abrams adopted a novel approach to secure the Black male vote, staging a series of events known as “Stacey and the Fellas.” This study delves into the discourse surrounding those events and their impact on misogynoir directed at Abrams. We employ a misogynoir framework to investigate the U.S. media narratives that Black women, particularly in politics, must redefine. Finding discourse on racialization, the masculinity of Blackness, and prominent misogynoir, our research sheds light on the communication surrounding Black female candidates on Twitter and their efforts to court Black male voters. These insights hold implications for future campaign strategies and discourse-centered approaches to political engagement.